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ASSESSMENT OF THE ASSOCIATION<br />
EETNEEN PASSIVE SMOKING AND<br />
LUNG CANCER<br />
YARELA• LUIS R .<br />
OE4REE DATE : 1987 .<br />
~-.<strong>~JiVIi~</strong> <strong>s«M</strong> .
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. . . . . . .... . . . . . . . . . . . . . .. . . . . . . .<br />
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'i M ambl.d<br />
'31[ISODCi AD S3IMQEIXJ<br />
.r+i++*+++r0 lAi 9= CIUI QN 1531MH an 537YHii<br />
SI=mnc S1Y tlw 3500$ att S5 ®qS F11U Hid<br />
5iJ.II81= v KiBfN W7M SUm 707 1iNo 9NR7 in 337VF D<br />
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Sall `.I>'1 WY ISI®pS Kii61i Qitl SlCmPiE 1OAM<br />
SUaters 'rn m1 '3=oas Zu. ne anas xru em<br />
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http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
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•c L'nMM •LW tlal : a'16p$tp{ 3LL NI S7IIIYSG 3il:SStld OL<br />
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http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
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IAnuits urtrs Aesup.ian 21 .<br />
Pigice No 1B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .<br />
aW= IN L'RJG G1lG71 LW DClJS Ml'1N PLR~'LN/YFMS OP mompL<br />
?0 P.-SSIVE 9dd!@I'i -N TAE 1CUg]GTD : fOR ALL SUd.'TIRS,<br />
NLV1R SPOIORS, AND FtFFER 4flF7RS : AND ILO mD5<br />
FL1P O sI'E'.7V1f CIi1".WtffS OP IX7C5fLlE<br />
( 1L•sults uo drs Asu puon 2) .<br />
Pigure Fb 19 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .<br />
O00>E<br />
70 PASSIVE 5}YXING 1N 1fE R77SppIDP Fqt .VL SUBIFrfS,<br />
PQOIE5 AND NPIFSt AND Fa D
NA 'Ilir .<br />
1 BF?.7~)!ID .<br />
t]OW3fA QE<br />
LI:fF)lH1M RVI1L1<br />
7n 19%2, the Report to the tMitd States Caqte ., on the iMalrhh<br />
Conwepxraas ot moleing fcr de first tiee gave sericus mroidrratioa<br />
to the !ssue of the e!fectJ of amiSrn .ental tahsxn smke an the nm-<br />
sideer (I) . Rtrt others besides senbrs tluselves orutd expsience<br />
deCimHtd hwalth effects doe to tah .cvo seoke Ird 6aan in the miu.is<br />
of nay for at least a deude. W.tetrieiAM in particalar seened to<br />
have im :m+ified this atcamp.tt.an, by repsring that cigaette<br />
sokinq rmmg pregnant woeen as associated with preman¢ity 12) and<br />
vith I.a/ hi . .•tlr.eiget (I) . Ather rep.xta attriauced a sole arrey, or<br />
adverse effeccs of aatemal smk4q m the foeuy . raeqinq frra<br />
Lticsire1 rxt-neral develacaent 11 .5) to rxqcmital arltornatiau f6) .<br />
Ieier studies acecAel to the effects of tohecco oaiocrwnts<br />
releatsM vKO the tTVirrivent at larqe . Fur inrJece, studies in tG2<br />
Lr1;ed states t7,5), flqlani t91, Israel Il0) and otMs cont_iee !1 .)<br />
sha .et ho . .hi1Grmn of wokinq parents had himri Lxiimx ^_f<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
.t<br />
/ respirat3_/ infecuuns, as aell as hiqh.G hoeuital adAisaian cates .<br />
Ie6ocatary imeetimticro sho.ed that expan:ae to setenal snoking<br />
.xaduoed a defective develop,eat of pilawty faTCtim in childrm, as<br />
m..eQvd by toroed expiratacy wl .ne in one secvd 112) . Finally,<br />
reports of cltildheod tuecrs associated vitti puentai mnkinq appenrtd<br />
ia the aediOl literature . attha.3h often vnth eontradic-.ary results<br />
I1J-17) .<br />
:Tnt there Kse aeriooa twlth effects aa the adiLLt passive<br />
seker - soeh effects as thase exxrieioed by the swMeis thmeelua,<br />
i .e. luiq mnc.r -- .n net cons:detad possihle as cecaKiy as a<br />
decade ago . This on be gathered fxrs the follo+inq paragraphs<br />
pi6lished in 1975 s<br />
'ln smn.ry, the effects of ci9aretta sdw m Maltty<br />
wn-mdmrs cwist eaialy of dror eye aqd tlanat<br />
irritaL`of . 6oia!oer . people with oertaln heart anl<br />
lvg diseases (wgine Pee[oris, COPU . alleagie<br />
astte.) ry suffer eoorzhacitn ot tlrir s"Pcois as a<br />
result of aspanun to tnnceo .dra-filled<br />
.mito.ena . .r (lp . • .<br />
• With respece to lung eancri there is no evidenoe to<br />
l+diuta %hetber or rot this leuel of apos¢e has an<br />
effect an the risk of developing lmq raiqer . xo,ever,<br />
tacau.e of the lw dosqe and trief apcsure, it .oold<br />
see . unlikely tJnt rlere wold be a siqnificanc<br />
i+rtw~ e in the risk of dr .elaQinq lung canee: • i191 .
_ t-<br />
tt is an establisMd fact that the overnll caaoer tist for nor<br />
Makers is lnrer than tAe emwer risk ot the general population 120-<br />
221 . Cainsrd to smkers, noa-srokece' risk fer cancei is alnut 50s<br />
la+r t2C1 . ler oereain sius -in particular the respi-atory tract-<br />
the datferscea are evea aece drWeric . A recent atudy, icietheless,<br />
hes suqgested ttrt 4eq m,noer an
2<br />
fYIDWlOfAGIC =1f5 .<br />
-5-<br />
Conttouersul reP .u'ts on len9 m+cer tsWs snony narsokers<br />
have rot been dixvaa9in9 enou9h to dississ cne nyPothesis that<br />
passive sedting - also tnmed lnwlunruy ssYdrq or sea :dery<br />
Wdkinq - i,t ausally related to luq M-r' LI Jamxry of 1981,<br />
the British Medal Jounal pblished the first pqr .laticn stvdy<br />
. 8izayum repor*ed :1"r<br />
sPet3ficelly addn+si'9 tlus iawe (25)<br />
fi-dings of a 14 year old prospctiae stF .dY %Auch I"°olaed a follwrW<br />
for 91,560 soa-smaking malcTSed Japatese %acmm• rkro hwIlred aad se`^ccy<br />
four msss of Unq canar• had develocad in this 9ra¢o for Mhic4 the<br />
tw6asdl aWCinq history had been colle•tM itdePdrlently . aoften<br />
earr_ed to hsavy saduKS 11r20 oiq .retvs/deyl s0owed a hi9lws risk<br />
for lunq eancer thae +ms+ serrld en nar-s .okats IstaMatdired risk<br />
ratio . 2 .081 . RirtieIDOre, a statisrically siqalfiaust doee-tespo:ue<br />
relat_w .shiP was fosrl : the relative ruk for ni.es of +-s-+ ca or<br />
smkers of 1-19 ciqarettes/day .as 1 .6 : the relative risk for heavy<br />
2<br />
srokers 1>•201 s.. 2 .08 (NUReI-extension X test ') .299 ; P, tuo tails<br />
- .00091 . 7fie tred rass also otwtved .hen h•s^wd
-I-<br />
letrn that in a sulsricle of 23 cases, 17 were aderocarcinonss . Since<br />
sdurq has peen posralaoN to be aasoclated with specific histologic<br />
typt, this infa+*Mt :^^ ~,1d seen avaal .<br />
Ompite the draWecks nrntiax6 aEO", thrze are •xrtain features<br />
alplt lilreymM-s study that CiKf it 1ad:fJ" afld plCtobly very difficult<br />
to reulicate . 'A(e prospective design inwlvifq a large popolatioa in<br />
aore uwo on e 9eo9rapwc region is certainly a n asset . Also<br />
advantageats is tln fact that the smdY ans mrried out in a<br />
tradltfoul society Mrs'e sioting hsbita of wum are low *<br />
tlus<br />
d(m: . .L...iry th e pro6 .bilitias of inclodin9 ertauaaly classified<br />
arnen Nn developed uncer of the ltoq as a awnsequenon of their ewn<br />
sakinq . A lso , ss( soch a setting sairrLqes my last longer . Aames are<br />
rerta'snly sah ~rllec . atd soclalixinq for roirn woally tdxs p~ace<br />
ir, the cmp.oy of theL halw :ds . All of the abwe s:qgests<br />
Trnti-`io(tlon of the Inn6srds' a .oki(q Aabita esy ffr3eed be a<br />
aeasae of aspcam to secvidhsrd smola .<br />
Ilin in 1961, hidup0olos at. al . plb lished the prelLMnery<br />
resolts of a stWy do,dactad in Gteeee (27) , using a nse control<br />
drsi9n. Ln ey assaebl.d a qra4 of 40 nm-sACking - dinpne+d with<br />
:Ully cancer in three lalys AtM.M 11WQifUls . lfe pGtietlts w~:e<br />
I<br />
intwnu.ed rmaedirq their Meta'ds' IDoicl+q habits aM yere ce :pnred<br />
r,t1N the ha bm6s~ saoking h .bits of 149 nomrdciiq trospi'al<br />
ca:trols .<br />
The<br />
car.trols aere ortbcpedic petients who did not differ<br />
si9nifimntly frv. the cssn with regard to aqe . eduratioo ,<br />
dcratiao<br />
of exr ;i .+?e, oxvlatien or resicWky . ^_te odds ratio for w:en Vftraed<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
that<br />
9ood<br />
to ex-sdoees w 1 .8; it w 2 .4 if they rwe m .rtaeA to curr,r.t<br />
enkers of 1-20 cigarettes/day ; and 3 .4 if arrried to cv[rent smmrSs<br />
of more than 20 ciqatettes/day . T7d .s doee-rrspuua txp :c w fowd to<br />
he statiatimlly si9nifiont (Chi-sq for linear trmd . 6 .45, p(2<br />
tails) < .02 .) . M :en espoe:¢e to hushuda' santilq over the murse . of<br />
the awrriage .as assessed a sLeilar trad .es cEe.zved . Fstireted<br />
odds ration .era 2 .5 for tlnw expoffied to 100 - 299 •ho-usar•<br />
ri9arett+s a(d 3 .0 for ttnae nsposed to 300 tlosanS or mre<br />
cigarettes ( ai-∎q for linesr trvd - 6 .56 . p (2 tail) c .02) .•<br />
Tis linear t :aM ~ idenriol in both grcop of oses : thoaa with<br />
eitological mnfiye•tion of tmor a :d *]nse with clinical diagemis<br />
o+niy .<br />
A later rapaR of ilidepaden' atody in 1983 aeided nearly as<br />
mmy taaes" and 5o6 anse oanrols, m w st'ry nmJacts (28) . ine<br />
results were •,^•••••••ially the saae : odds ratio of 2 .4 for dves of<br />
eeokers of less than 20 cig .rattes/dsy . .nd e31S ratio of 3 .4 for<br />
worrcn ms .-riad to smdeecs of acre tfien 20 ciqsrattes per day 1Ch1-sy<br />
far linear trend • 6 .7, p 12 tall) . .01) .<br />
'me Gree¢ atLdy . altlnulh rot enclrelY ooiparable tm that of<br />
llliayala . !)b. ." similar rfadlta . It also s11lres lpn: Cf t11N adVantaqla<br />
of the latter, n .rtly' tlsse oonoernlnq fasily atrmaora and fanily<br />
soeiel lif .' toqMhe- with their IaplicKions on the aswaent of<br />
eqxnore . as amaroratad apws . Differr.t aetlpdolaqical pfo6lerm .<br />
h-er . ou9ht to He oaniderad . For lrotanos . Ue study qtoq, is<br />
saell and tIC de9ax of p.vuloqieal OWim .tioe poor IonlY 651 had<br />
a citoioq .ol or ur,aloqiml diagncsis) . 'ms stody sonjcccs (nrn
)a<br />
yrotiag ypmn vit<br />
.h long cenczrl [epr~t aGOUt 78% of all the fanale<br />
!mg mrwsr uses diagrneed in Che pesticipetvq MaPrtais<br />
. ns is<br />
sentianed in a subsequeut . sectim o` utis cAspter isee : Oiscoloqic<br />
:yoe ao! 4slq Carcer) tM1e Propor"-ioo af noo-sookvm patients in other<br />
series of luy cancar cases has 6een "subli'aherl at ahout 10% for<br />
~ . The esassisely high ProPortlm relnxtrs' by T-'icbPo 41 Psck+ of ciqarectu per year (aa .<br />
3 .11 . p < .05) .<br />
Iepoerent drawsrke rai be found in the study by ltlayu Cortea<br />
et . al . . Its uin dissdvantage is the fact that the asehei of<br />
psrtrnpents is so sawll that any of the possible strRWqt .he of the<br />
study -- wch as the 1005 histoloqic emfixe.tim of dSagroai.-, -<br />
fail to aaFelnate for tlLL+ wMess .<br />
A mcre recant epideeioloqic stody m the llaq caneerpassive<br />
smdcinq ralatianship . .s carried aR by eerfiNrol . AoerAsN and<br />
Joubert (30) . Their qrolp of cases w wprisad of e11 farele non-<br />
arokuq lonq canosr patients diag'osed in three hospitals in Nev<br />
Jersey and en Auspital ln OAio. he~w~ dt.gooswd with aolm rwnoer<br />
se.wed as controls . _Tree metrols were sateMd to each case m t he<br />
basis of age 1-5 ys.rsl and hospital of di.grosis . Patioloqy slides<br />
for both ceses and xntrols .ere revre.ed Clindly in order to caMiim<br />
the diagtbeis . me tnmdred and thirty four lug rancer cases a rd 402<br />
mntrols .ere tlm uxert:e.ed regarding tee ssokinq habits of their<br />
t+wbaed+ . CUrre'rc saokinq Aanits, nuRher of cigarettes sad .ed at<br />
hrne, and mnoer of rea_-s cse As6a:ds esd ruked .ere assessed .
-11-<br />
SinilarlY . .a .en wre quest:a^ed ahwt me mm°er of Murs a day tneY<br />
Md oeen exmmed to the siroke of otlrrs in the past 5 and 25 years .<br />
it wss foud that wwm . sarried to ssokars of 40 or sore<br />
c_garet[es per day ned an cdds ratio of 1 .99 1951 Qa :1 .13-3 .501 as<br />
crnpsrel to ttcse nrrried to narsd:ea . If half that asoimt of<br />
ei4arettes .es smoked a= 1xme, the adis ratio was estiarted to be 2 .1!<br />
1951C.:1 .13-1 .951 . 5ladlarly, an increased risk wm foond for chme<br />
„rnm netried to sen %s:c lad san :ed for 20-29 years (OR - 2 .21 . tut,<br />
mamerraSly . sot for t1c .e ssesid to ndasra of snre than 30 yesrs .<br />
fb incsea .ie of risk vas foud to be dependent ae the :sster of<br />
e:pcauTe-•Iqors 1n th last five md 25 years .<br />
tsiny logistic rnqresstan teciniquss, a scdel w fitted to tie<br />
stody data . The arasal incloded tesss for possibie m+fouders and,<br />
ser.ral m: timroos tim variables repcesentL :g<br />
espon:re. M lnaeese in<br />
roos risk with inceastrg espaeore ess foord for the nuMer of cigarettes<br />
srioloed by the Isnbsnd at hmr . 71LLs tzad .as statistiully<br />
signi!iavn at ths 0 .05 leuel .<br />
7Te study by GarfiNul et. al . attepted to tadcle sase of t-he<br />
aethcdololical pmol" ptesent in t<br />
.4e forsez ttodies as passive<br />
s :mlci0y, ;fie authors .rre socce-tsfal in pottinq tagethez a sirnble<br />
5co,p of cases Nro •r-te emfiraed neuer-s:mcers asd .t:ose diaqnesis<br />
wes nistolo3ically eesfircwd . Yheir assessrcnt af espoaute .as net<br />
1lmito:l to the ab:e derived fras the sus6n .'+ds' moki .-:u but ineluded<br />
_'at . .e~perunc~d at the<br />
.otbite and a_hei areas. !b.er:ul<br />
s :atistacnl tec`nid:+rf (logistic reqressioe) .ere used to ane! ;ze che<br />
9e'n, ord~v+g results c^u'-armt<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
.ria t~e f :ni .iins of c~e tw :.:xr<br />
-12-<br />
mejQ rcudies on this tcpic . It seme, t.he[efore, that the onay<br />
aspr of the sndy rhat ooold have affected the resolrs is tnat ~hics<br />
is acst diffialt to esaluste : tte reliahili-y of the data oollected<br />
thras7h the iMerv~ . fven efo:rp7 tle ilR.erviwwia .nse n¢:asedly<br />
blins in relard to tla i:ypetleai, of the study and the casrJantaol<br />
stetos of the paRScipsta . the psrtidpeKe tlrmelves varo anre of<br />
ehsr awf oonditioa . In Nis altuatiu: tte posaihiiity of<br />
o`TnePorci+9 by the mses mt be porne in mird . Ildaitionally<br />
lntentieaa of surrogate respes :dents msy Ie" affeRed the reliability<br />
of the informstlos about the esaaeure variable . In fact, lAeoel (31)<br />
has slo .el that Carfinlat'a eeMyrtaa of tLS addm ratios vary<br />
muiderably aocolding to the type of s.apvdsrt. Bs foud that ih<br />
odis ratio . for lug canmr ra 3 .51 19ls Q. : 0 .Ba-15 .281 in qr<br />
nsHrnw !n'hidh the sesP+de:na sere elttAr a dayMer oc a aon of<br />
the stidy subjecv . In the w :bgotq in Mddh tle lsobnd providsd<br />
inforaetiom on the elpwn¢e he foud that the odds ratio w 0 .17<br />
195sM : 0 .56-1 .06 . 1W finally, in tas wbgto:p of cases wte repecead<br />
a6wrt thel.r o.e espeau[e, the cdds ratio . .s estiaated to be 0 .e1 (95%<br />
Q. : 0.5e-1 .301 .<br />
At tM ssie t=se that this teport 4as beiml p.epsred, twu<br />
additiwl epidesioloqic studies olaiauq tne existen,, of a .odente<br />
effer of passi•'e smd .Lq m lueq essoer riab rese published . The<br />
first of the.e .as also eond.Red in Jap.n 132/ . It is a oex- oont.ml<br />
stuty, hut, as Yas tiue of its prede¢lor, it r :eMes use of a cefiRt<br />
i .zit.ally defined for .roCyr pocp:ae (rh study of the effecr.s of<br />
atcmic radiation in 4i_-oaai . :~ atd %~Yasaici sun•ivoa•s) in ont' r_o
-17-<br />
oorein its stedy subJecs . '1he cd~ort, c°'4r-'°d cf a6out 1101000<br />
xnplew yielded 525 cases of lun9 ceacer becween 1971 and 1980 .<br />
patholslic diagnosis vere drne in 37% of [hese<br />
. Castrols yere<br />
selr_ced fran :iie same ortqrt asang wenibet's<br />
.+'n had not develop lunq<br />
canoer . 1ye centzols<br />
.+!re Ldividually s+tched to the mses wuh<br />
regard to year of birth I+- 2 yrsl, resideiee, sec, vital status, aM<br />
,metrer or not Lh<br />
.ry had fielooqed to tlu ranrt sutBroup Uat unY.x.a+t<br />
. Inforn+tion m+s obtained for 428 cases<br />
biennial mriial eumisations<br />
ard 957 contaols . No .emer, oety 19 sale cases aM 94 f®ale cases<br />
occurred amg roa-ymMe_s . fwpiy the non-smokiny msles the adds<br />
ratio associated with hwin9 a apane `fi° woked `°s 1 .0 1901 CL~ 0 .5<br />
- 5 .61 . For females the corraspadiM figure `as 1 .5 /90t Q.= 1 .0 -<br />
2 .51 . In a3lition, teieles slsa.. .1 an increase in, riak of lmig canoer<br />
with the ilCressing nalrr of cigarettes by the Mubud<br />
; the<br />
odZ+ ratio ceing 9remter than 2 .0 for the highest espomce care9o[y .<br />
1fie test of linear tra'sy, hawser, rs not s•a"<br />
:imcally si9nitiont<br />
at the 0 .03 level<br />
. Likawise, another nwwts of hu+huids' mdcin9 -'<br />
the rnnber of years the husband ~clod - . .s rot statistically<br />
siqnifiwnt . rLrlly, their rswlte sha.d that nan-aoking wmn Mn<br />
had peen eqn .ed to tle 1snLSSk' nckln9 in the lsst 10 years OsE a<br />
lo.er risk Wit e 1 .3, 90a G.t 0 .9 - 2 .ai than those aaen aRceed<br />
within the last 10 yesn IOB - 1 .6, 904 Q.x 1 .0 - 3 .21 .<br />
9aR of the ahoue estLutes are cwistenr in their nwgnitude<br />
•if net in their statistical siqnititancel ritFh the results of the<br />
!sst Japlrese stody, as wl : as Mit .h the ct=et stu8ies M lassive<br />
xm . ;ny . :!a .ene_, this suWequnt sntoy equelly shares in sae of cY.e<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
-1,-<br />
setlndoloqic plvblem that cast doubts ower-their results . one w=h<br />
pruolem is the pxr rate of histologic omfi
-15-<br />
signifiauft<br />
. 1NL~tiunally, 90\ osdidare liRits are reoarted instead<br />
of the earon.i 959 a. .<br />
. klthw9h fsdn e nettqdologic or<br />
statistical Pnint of 4feN there is lOthin9 wror) with this alproath .<br />
it raiVA Cmtern Shst rese~-'d~Ers<br />
. i9 o[dQ to detrct ud re[+rct<br />
'siqeifiamt' efters . sey take the risk of aoo¢CL .9 a qrester mle<br />
of caanc4 in their !Ldinqs then tnat whtdi is oanleotionally deened<br />
apeaqruts .<br />
1fx sxrd arat recently published article is based on the poolzd<br />
data fran three case-cmtrol studi.es ()]! . .A lnety nLie histologically<br />
omfiz .ed lung tarcar rasea nd 736 oonttols omprisd the study<br />
ytuy . These vrre all the participants in smdies ewrzisd out in<br />
;ncsiara . 7"a
-17-<br />
wrm meraxd cc nm-s*rJCe .-s . '1=e rate ~ only 101 iug :rr `or tMee<br />
sarried to a $m*er of eure than 20 cioa :ecte pes day . :a~<br />
oadoudinq variables `wre taken into acodmt laqe, rac¢, edumtim,<br />
reyidence and ry,ysbands• oxtqmt .ion), the eaRSS risk vas 371 and e1,<br />
rewectively . Noix of tlrx findings .ere atatistically significant .<br />
lk~ . the resolts have to be interpreted with great cautior. because<br />
the rt¢y w never desiqned to ebenin infon :~on an lmaive smKuq .<br />
PqrtBecaore, rhaceuer sedrinq intomnttan res aaailablc carespaded<br />
o :ly to the exposure at tfine of earollsent into the sttdy .<br />
Li6st and wynder 1311 assessed e:@aaite to seoxHa_'y s:mke in a<br />
suMet of :v :,kirA patients included in a large sody of tabscm-<br />
related cancers . Oot af 2S sade rases six reportd esposure to ocher<br />
pecple's aol:e at hone . as mpseed to 5 oit of 25 oarczoln . lYqrmn<br />
e( ttssse eases nWSted eRasufe at work verss 1l of the aurcrolsS this last ditfezence wws barely statisrlcally siynificsait . Aasq tne<br />
feale g.aq (m'S3) abaR the saee Ittapurtion of eeses and cmtrols<br />
were e :preed to oHrt pecple's >odee at hal ad wctc : omsequertli<br />
the association with lunq Cancer w nac .seatiaeially siqnificant .<br />
Sandler, et . a1 . reportad tlr, results of a casreantzol study<br />
ia•nl-rLq Sle r~r pa'ierKs (all sites, eaotpt basal-cell rancxr of<br />
the slcin) and SIB controls . in three separate publiatiars the au.hers<br />
assessed t .he association l:etwee~ tt:ese crrxrs aid : 1) emcsure in<br />
clutdnaod and adult life to the ssokinq of all !coselwld nedtrs ut:o<br />
smked (351, 3/ early lift fte to parental sadci .•i9 (36l, aM<br />
31 e:qasure in adaldnod as a resolt of spnuse's saok:ag 1371 . in the<br />
: :at of t.tiese --'e odi• ratio for t .Sae e,-csed to one s-nvr<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
-LS-<br />
in the houxhold ees fomd to Ce 1 .5. If e:¢oswd to the moke of tuo<br />
indivi.luals, the oQls ratio inaewted to 2 .3 . and to 2 .6 if ex;ioeed to<br />
the snoke p[od:nad by three s:mkers . Tfiis tred was statisticalll•<br />
significant (p < 0.01) . Ba..ecar . it Mould be noted ttut an in¢ease<br />
in [isk walan uEsetv.d for active avokers .to pad been espoaed to<br />
the svdce of otts!rs in the Aasetold .<br />
11e overall unosr risk for all swdy subjects (passi.e . as rell<br />
as active, smokets) Ws reported to be elevated in both of two<br />
circwetaz,oes : .i+ei expoaure to setvNary sadmd had ocvrref dorinq<br />
d:ildamd miy IOnal .61 . and ,Aen the emilmMifte took place in adult<br />
life eslu.iuely (OIal .51 . for an individual espased in both pericds<br />
of life, the odds ratio exceadad tvo 10R-7 .7) .<br />
• Ibr the seoond repo
-le_<br />
race, sex .-ed,mt3on, or oocluetim between cases and cc,rtiols . Mr;.i<br />
sue-speclfic cancer risk was asscsed, the authors found that exprnad<br />
individuals ILbse married to snokers) were at hiqher risk for cancer<br />
of the Faeasst laa1 .81, of the finele genital organs Iaftil .e), and of<br />
t11r_ efdocine systm IaN-3 .2) . Buad on a wnll nnher of caece<br />
In- :21 it w faad that passive sdkers shaed 1 .9 tiaes the risk for<br />
lunq cancar than these nor espoeed to seemx1herd sso:e . :Tis finding<br />
did net raech sutastial siqaifiona .<br />
There are mainly three grobleiatic features in Safdler'a<br />
cubliwtims that deserve eane atterrticn . The first relates to the ry<br />
in Ndch the results have bern preseitad . In aany instances the risk<br />
!or oncer associated with passive .mki1q is presented for the Mnle<br />
study qeoup . cceprising nm-seokers as well as asoixrs . AItlnugh the<br />
lat•.ier graup carr be tauidered passive mokxrs of their rnm se=Ndary<br />
smki - as well u of the sadot that othem promce - their<br />
inclusion seens inappfepfate, siire the ovatwhele'uq effects due to<br />
direct ssokinq wald tend to distort the effett due eaclmively to<br />
pesaiw amadrq . Saas tables, hwnner, do aeke the distinct .ion<br />
between the two gcoRa, and those ere the ones that are emst<br />
infometive . Secadly . eonfowdinq variables that aey explain the<br />
o0setved associationa were not taken into aemunt . Soae of these<br />
+a:iahies nce exmeure to alcohol, .to ooagational hafards, to dtuqs,<br />
and to sexual and reprcduttive behavior variables . thirdly and<br />
lastly, the fact cnst an asocucien .as tound between passive svoking<br />
and cance-s net previously deserihe7 as tohacm-relaud fhreast .<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
syrem : raises srne suspicim . This fiidinq :ay be a<br />
- :o-<br />
crnsaryenc! of the inability to cmtrol for 2mfo,mdrls, aa mectiQatd<br />
am e .<br />
In additim to the epidmloloyic stdies, lahocatnry<br />
irnctiqetions, aloq with clivLLwl and patholoqical observatirns,<br />
have suppcrtad the hypcttesis that lunq cancer and prssiaa ssokL~q<br />
indeed eay be asaoeiated . The smt relevant literature in thne arens<br />
is disc.used in the follorsg paragreEtis .<br />
4 1l.FfJPNSONy INVGYCIfJrfIDNS<br />
mth obaervatimal nd eapesisantal lalrxatory studies iuve<br />
praduoed valuable infornetton on the biologio .l plausibility of the<br />
health effects of pssive sadcEnq . The amat isportsnt findings ere<br />
related to the identifiatfon of orcSnegenic substanees in sider .rea,<br />
smke and the ability of sae sideefie® saoke componefts to enter the<br />
oiqanisw of the passive sw,er f3W5/ . Cigarette a,dce omtaLts ower<br />
ane t)outand substances 116/ . Many of thea . including o¢cinoqelL+,<br />
are present in evan higher mioentrations in sidestzeam mn*e than<br />
mawtream snoke . fbr instmce, Diacthylnitraamine, a petent<br />
carciaoqen in aNaa :s, is 5, twros nore ooncartrated in sidestrsam<br />
meke 1a7-181 Bfweienn, et . al . /191 have estimsted that a nan-<br />
smoke : Mw apaLLi ene hour in a smky coon oay L4ule nitzosamurs in<br />
(Tuantities equivalent to snuking amut 15 cigarettes . aenzola)pirme,<br />
another knan carcinogen in srm asd uu .mals, is present 3 .4 tiaes aa<br />
,r.,;t^, i. ;idcstc~ sneke . F1rthermore, ene ci ;arette nay relmse up
-21-<br />
to 100 nq'of tmt substence lato the air 1461 .<br />
91t ho<br />
.w mrll mq,•' to these subetnnK¢s doel the reqular mr<br />
smokiry perfa : really erpesierm? This has beP+. arsy difficcvlt tn<br />
qrwn•Sfy . 'O+e oooartSations of tmacm oouponr+rzs in t.he emuanat<br />
tepet.is oe rnveran faccees<br />
. The aeumt of tobaao camaxd, the<br />
valune of aebieot air, the size of the :oom iArre swkin7 takes place .<br />
aM the type and aeamt of veiLlatien in an rnclosed space are soie<br />
of the aerl variables that affect sodce intake . Dr prWinity Of the<br />
passive sariter to the swtoe of sabks aed his/her pattam of<br />
iMalarian ery alan affect attu .l e«pes.ue 4491 . siailarly . the<br />
amkiig patterv of the individuls Mn do tire smkinl need to be<br />
oon"dared<br />
. lyr i••••••••••, the vatiatios in poff frequeoc,v . putff<br />
duatton and puff volwe an knwn to affer borh tre dmmiwl<br />
oompaaitian of sidestraem 4oke and its bioloqiwl activity (S0-sa) .<br />
Even the srtoker "s health statos sam to affect the wwy in<br />
.Mich<br />
sidestesa ssake is ptoLOed (55) . In faet, it is the sidest:eam<br />
senke that has bsw sydl[led by tta above ard uttrs factors t .hat<br />
oanrtitote t.1n ree! .MQonns to the pessive asdcer . Sane autlars<br />
prefer to refer to this as emiromatthl tobscoo sdoe raUer Uwl<br />
s :jestleam smke .<br />
Desoite these diftlcoltin<br />
. sae stuCies have attenxed to<br />
quentify actual ecgosure by mesrain9 tohaRo aetabolites in had!v<br />
produ«s . 5er,p<br />
:byacianate ard mtinine are found in the blood,<br />
ur~, ' senm and saliva of the passive seoker (4S . 56-60) . Ntl+oqh<br />
iiycriarote msy molt ![an otl+er sourre - i .e . leafy veqetables -<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
_2=_<br />
caunsne is a specific aerker far eeposure to tmecnv mwke nnd<br />
therefore its preseoce in the nomaQOkeis is ta .er- as evidrnte of<br />
pi+sive imela•ion . In one esq,eriment a researcher ves also able to<br />
identify nKegenic wlsunoes in the orine Of aocje~zs eiposed to<br />
swke in a prxaly ventSlatai rooA (60/ .<br />
6tudies aieed at deterasininq the apecifie de(asition of<br />
envi . ... .. .. . .~ snehe ceqponmU in the lurq tissues are very sr.anty .<br />
In tlr.my . the biotogiosl feetaes of the aurtary aM pAysyoioqy of<br />
the huaen reapiratay systm . ud the physiml and tlamiol<br />
cMracreristio Of slEestsese yoke, nqgest th+t sarL deposition<br />
takes place . The este0t of it . hv+eaer, has bxn a ratter of debete .<br />
oi_ferent aotlsas hsve remeted high levels of mdre bronrhial<br />
depositicn ranging Ira 116 (61-62) to 606 (63) .<br />
ConvrrselYr peli .ce aM Lorty (66) think that pt passiw<br />
s^uYers an espnsad to a m4dw1 asant of asoke . peth.ps m .~. than<br />
the qoivalerc Of aee ciqarette per day . It has been us)qested that<br />
a" en erpccure oonveys a negliqi6le risk /651 . Mith respect to<br />
aLLs, it slwld be sord tlrt tq treYnld level Of asposice fer the<br />
develouent Of lisg runoer has Eeen established . Therefon, any le~el<br />
of .xPoaire - incloSfeq the low leval attsirs.d by psasi.e snyLiip -<br />
slnuld be oostiderd pota+txally able to elicit a qreirvlenic<br />
rest.rrse .<br />
Another s.ties Of studies have been aired to dete .t the .f•.eccs<br />
of pessive seqkyq in the respiratyy •uKtioo of pusive sekers .<br />
'M1is la particularlY relevant since saae aotlrns tbink -h .t an
~•'^('4« ..:ez<br />
iaosi.:,d ;espira-, .arj<br />
_21_<br />
fwcim is in itself a risk fact..-r for linq<br />
caK.er (66-69) . In ftant: . Faoff:ren 1681 ot . al . oonoared sPi-'o'etric<br />
nesaceeents oet<br />
.reen tw types of nai-wokers, eKrosed and nm-eqosed<br />
to secadary >neke . M11ey found that mth aen and .caen nerziG' to<br />
ymsers of r 10 g of tota .m a day hd a siqnificantly lort foroed<br />
mid-expitatory `ld rate {FL" 25-7SI then t .hoee auried to ron-<br />
mc.e.'s . In additiot, wnen in the expmed q :oi4 ats*a~i a decrease in<br />
forced ex?iratary volwie in one secmd f?£J 1) . The stud9 ffi-=fui :y<br />
cmt-rolled for cmafomditrl variables surn as aqe, sotial class,<br />
eduatiam, family size and air pollutian .<br />
Wtite aRl frotl> f69) eeadueted a sady in %hidt the effects of<br />
payive sradc'vtq in tlfa wrkPlaoe were asaessel . It aas fouM that the<br />
deczeasm in ferce0 mid-expiratory and end exPiravay IFFY 25-7i and<br />
!L
S Ap'IIMAL M FIIIIOri5 .<br />
-25-<br />
7estirq the hypethesia that passi.e smking ani lunl cancer are<br />
related by amens of animl -quriaenra lnrnolves sismilar difficylties<br />
asei'ad to the stsdy of the oreinqmie effects of dir!et saokinq .<br />
44e search for a suitable ahiael .odel has taken smfy yee .-s . nd rhlle<br />
researc-s are able ta reFrodiea msny of the respirarory s}stea<br />
tumn . ro oae .wld claimed to hew frsssf an ideal .edel .<br />
N~, eaan vittiam interdinq to do so, away of the w .periments<br />
aised at snslLq the effects of direct ssdcinF aey inleed have heea<br />
test,sl the effects pmdmed by pnsise ssoking . Various spedes of<br />
la6oratoty anla.ls laice. rfta . syriah hrestersl have been<br />
esperimennlly expesed to .rcJorfilled emirauEnu (72-75) am such<br />
stody (72) now ovnidereA a classic in the field, has slwm that<br />
ratbits ex7iosed to eavirvepKal avoke sry develop ttachecbrmdhial<br />
eptChelial aetaplasia ard dyspla.L . This study, along with the<br />
otters rhich follo.ed it,<br />
.ere interpreted rlth auch rautim since they did act quite s/aallared the phe~am/m they were iateMei to<br />
stody (i .e . the effects of direct ssokinql . Different but equally<br />
iapcrvnt oeests should be taken into crosideretim N,en these<br />
studies are used to drar cmclutions ah= expmore to psssi•.re<br />
udcnq . For Lntwrre, ee cannot be sure thet erirsore to asoke in a<br />
closed e!swber actually sLe.latas passive mo" . mr tFat Cs<br />
amta .ry ard physiolaqy of tm respiratory tract of the ex@erLne ::dl<br />
aeumsls wWd :espord to sacvdazry s+*e = the saae .e- as hwnn's .<br />
fbre re :ently . nFoistitat-t eaAirnv.t that ?roduces ani traos<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
i<br />
- 26-<br />
sidestrean smse has been de .¢loped to sLnilate ex;msuje to Mnle<br />
ymke or to its qu phase only (76) . Such devices inclode emposore<br />
rsaaoers for roiemts, cell cultures or isolated perfused lmgs, as<br />
.ell as mechanissro to senipulate aeda roluae, dilutim . ad oriMs<br />
variables to be stodied . 'lhese denioes are rcmt yet part of the<br />
staaderd aqulaeat af speaaliaad laboretories, but it is likely ttxt<br />
their inttado¢im vi11 prodze a reslth of lcorledge regarding Cx<br />
effec-s of udescteen sdre .<br />
testly, saay studies have presented evidewe of Ce cerdmgenic<br />
precerties of toha¢o ampomenra .Mn admi^ :s'•M throxJh ra,res<br />
otlxc c~an the respirstory t .-act- lYny artieles m the effects of<br />
suhwtaxvu in7eetiens ef tdacm ospments 176-'l7I . along with<br />
artic!es m the effects of rubbinq ud sklh painting with te4c+m<br />
ctepourNs 1761 . aqree that there !s little rmsrn to doubt the<br />
careinolenie pxoper•1es of toosma sede .<br />
6 S4AQDG NID HISIFdAGIC TYPE aF 11R& Qlll9t<br />
An oheer'atien that has created a qreat deal of intexset aemg<br />
r.+ ..n++e .s crnterns differenees fomd hetreen knq rsuioer ases in<br />
snokers a,d lmg caneer rases in nonsmkers . These differeaces<br />
pecrain aa :nly to tw factors . sea and histologic type . lfae relevant<br />
li_eretore in this sobjeR is discussed in the folla .Lq paragraphs .<br />
Mong ra,en wtl1 lurg tanoar there is a higher perrareye of<br />
la.sucMrs than ananq sale eases . ln upper tw York State - as
-27prelimWry<br />
infaeetivm for this study yes bein7 M1ier .'sl - w fwod<br />
t'xt nawmocvig ~ conPrised 9 .01 of ai1 feaale ases, .beress<br />
tntymkuiy anf repre+ented only 2 .0% of ell eale caves• Osing dats<br />
published by [SeNzr9 ee• a1 . f7B1 . I estisated suiilar figures . In<br />
their series of cases . 10 .71 of t!a wrcn .are nonsrroMers verw 3 .0%<br />
of the ec.r: . Ymn data prwided by F .ot and y+derr /311 tle estiseted<br />
cnnesondin7 figures an 14 .96 and 1 .90 . Finally, GsrfiNcel et . al .<br />
raporred that 12s of the fswle luq raeoer cases saeened for<br />
psrttcipstim in their st.dy (301 .ere ien-sdters .<br />
I_ has been wggestad - sinc< ferer wmee than men ssoke -<br />
Wt a larger ptoportion of females an left sueeptible to the effccts<br />
of otisr urcino9ms ilndldiM seouelu^d smlie( than to direct<br />
cigarette sm*e . 7bese c,teelnegens .wld be respaoible for the<br />
'exQas' mrrber of no>asaikinl fessla caxs . The effects ef these<br />
carcieo9ens in een so+ld be sasYd by the ouenAelaing effect of<br />
direct ciqarette mdce .<br />
Histologic type has also beei reeegnisad to be associated ua--4<br />
sndcieq habits . Tr roaae of this asociatirn, }w~r, reaaim<br />
controversial . As early " 1957, Doll et . al . f791 had pte{esed a<br />
'dose-respaee' relationship by sM.ir.q an assoei.ation flecween the<br />
aeasrc of toEaoco mosed aM the deaelcl7*nrt of e ;ademoiP.• lary_ oell<br />
ad sall cell otreLrma . f!ther listnloqie types uere faad to be<br />
either or.:elated. or only sliqhtly relatd, to snohLw_ A feu yenrs<br />
:ater . !cre.yoetq wblished similar ehsetvations f8m . He foed an<br />
as»ratir. Y_-.em viokinW ard eprdenmid, lae" c^l : aed smll -e_ :<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
-2e-<br />
ra.-cimsee, similarly he rejected an assa :attoss be!wers, smRanq and<br />
bot.h adanrarcimss and Lrurhioslvectar ca[ :i .nie .<br />
Ils then os. w arthoc Irs fully agreed .dth any other,<br />
• preaentiog reaults tlet are ofun frarJdy contradictory . weiss . et .<br />
al . (611 in a prospxtlw sudy of 6 .163 sen, added .~+MTinae to<br />
the list of histologic types related to mok : .q. Yesner (62)<br />
cmfixmd the asseciation beoem aol~i.~q ard mnll cell ortltneu,<br />
hut snt with other oell types . lroerb.ch fourl aok:ng habits te be<br />
equally distribuasd in all eell types, tturefcre deryiog any<br />
aseociation beywen histology and tc6amo amoh. 183) 4inmnt cvclodes<br />
thet adenwarcimr and bmsbioilvaolar carcLoss ate irnenely<br />
related to ndcin9 itll . Atd . acte teoatly, be lnleoedett atudies<br />
have eepn•eed that a11 c.ll types. including ~ . are<br />
related to agsrette .okleq 1051 . '<br />
•1Ae difficulties in interpreting the results of theee sndies are<br />
many . 7b in fartia+lar, ticrelar . deserue to be mrntioed . First,<br />
there is the ptobimattc drrecteristie of the study 9rThey<br />
m,prise such hetereqews - and selected - populations thrt<br />
pasible saeple bias is difficult to ignore . Seasdly, the<br />
LxerveR.ion of so meny, petholoqists in the rwit..inq of the slides<br />
brings to mind the liYelihcod of Imreliability, of diaqnxe . . It<br />
slnuld also be added that the studies mer an ••*end-+ period, the<br />
oud fifties to 1984 . ourinq this period the ability to assign laq<br />
cancer raxs to soeelfic histologic types has clwqed . as on Ce<br />
assens.d by tx :.e.-erosing nuMer of casc diagnosed as
In<br />
wdiffereneiatai ^el1 typn .<br />
A msa c ;e.•rc assacia[_on ' s fou:d bero,eer: hl.stn!oqic :ype and<br />
gpX . MG6t studie9 a9tCe thet epideifrcld rfl'^llYllla is TJCe frequOR lf1<br />
ma!es tlw+ finela<br />
. 7fie pivporcim of male raxs classified as<br />
epideeroid earci+nies nn9as Ue*.ween 381 qu1 64" wr fe :mles, the<br />
val :xs are 6etweeA 21% end. 551 . 1Ye ottrt notabie dSfel~- occ.as<br />
an,,4 ademurc~mies : this taor is e=h so:e mnm : evrrwl .aien tlw,<br />
nm . ap to 52% of a11 1 :m9 earner casa in faftles have bem repa'tc1<br />
to `slong to these qraip, M~ 331 is the highest aavo9 aen to be<br />
pces,ced in recent studia .<br />
17w differenm in tmeki+sl eabits Cet .een seA and .omen aulgeses<br />
dre such iubits s .y 6e raspotnlDls for the diffeZms.a in histoloqic<br />
types avq the .esu . Oefortontaly . this has net been pmperly<br />
assesasd in any at•* . Nast reperts deal with the sex-hinnlegic<br />
type, or the s+okilK''l3tolegie type .a.otiariam. 2ne thier+ey<br />
interacrlon, xx-sdcUq-histoloqie type, reawins to be studied .<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
. aGPIfR W4D<br />
In Anrii of 1982 the Ner York State ptpattmeot of Health<br />
initiated a latqe stidy nf the tpldaefolary ot luq oen'i . t!w York<br />
SGt., with appmximstely 10 .000 oses of Wnq caneri reprsted every<br />
}rar to its tumr registry, ptovided an e>mellerc setting for a stufy<br />
of this natore . The pmject wes intaided to be emprelx•naive, that<br />
is . to intiode both snokinq and nat-smdcLq long caneer cases . Stsdy<br />
of the q[oup of sndcing cases wes limttad to the clinidl ard<br />
patAolo9inl cfur .c.e.istics of lunq canner, .heress the asses>fne :t of<br />
espnsure to passive sndciig ad other relevsnt em .im.rntal variables<br />
w:re the mein study variables in the non-s:rqking The ruay<br />
design also d1iaC for a population based mse,rtdrd emtrol groop<br />
(this gM'P wil l be descihed Iater in full dereil l . Lt is only clese<br />
~ lattel qn .xps - sm-aiokinq cases and their wtteapordvnt<br />
Mtdrd ceetrols - that will be used to assess the effect of<br />
eW:sure to paesive srokinq on t,rye risks of lJry caKer . 1Te<br />
-30
RG4N;dJlGQ1C app[oa-" '1Sld CC J'JS eld is Che C11eKO'QR rbtCMYI c3•le<br />
crnt_ol study. _<br />
It aay be pertinent to eentian tlnt the ariqiral desiqn of the<br />
st<br />
:dy specified that, in oper to disQra aoce precisely the effects<br />
of passire snoi :iat oa the risk of dew:aping lv:q renaes . all caaes<br />
u:cluded .wld be never snokers . 1w tMn9s were clear early on .<br />
9wevet<br />
: firscf that aale cases eere rarely never >nokers (cnly 2 . 0%<br />
of cAose initially saeend for iLclosim in the scudy rel .nrted to<br />
have aever sanred) . ard se .vd, that a sofftcimt mwler of these<br />
r&ses mWd for pes .ibly be asseblad in a reaxarohle per?ad of tiue<br />
so as to satisfy the ee:ple aite req:creRnrs . M1tmreCore, the<br />
elegibility eriteria for r .ses uas ncrraisd to lwlude thft Nn had<br />
stcppet saddrg at lent 10 yaars befote dia :gnsia . It "d ttbn be<br />
clear tlxt rRrn Ve refer ln this tepctt to tJr qrwp of aoa-su(wg<br />
ease.s . we are refereinq not only to never ssokers but also N forner<br />
slmkers<br />
. 'Ihe iupliostials of the deWicn to incWde forner sokers<br />
in the study 9ivuB are discussed in the later sectio : of this C+apter<br />
that deals with serhods of anelysis, as<br />
1 a61E.'PIV6 .<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
.el l as in 0oprer rour .<br />
itx sayi nLL-7 ose of this stv?,i w tc e>mixe rle relationship<br />
xr .ees xssive ankinq and llnq ce'mr in non-vmokers . oxn9 a ose-<br />
cx :r_rol approsch . Taa w tal! by alely=iag c'ata tallr_t~d in 439<br />
cnes cf lvq t•aqrr aod 439 metUW "healthy population ~ls .<br />
The specific questioa addressed in tLe analysis .ere:<br />
11 Is there a risk for luq ~ a .sQiared vith tlss apSnes'<br />
ssolNirg hshiXl<br />
2( Is r .Yle a risk for luag osnaer aaaeciatad with mmmk.~ng<br />
haaits of se :6ars of the Iwse:nld lirclusaw of spaael?<br />
• 71 Is aKpcaute to passtve mkiay in the wirlpl .oa asea.Hated<br />
with a htgher risk of lug cmOerp<br />
11 Is passive amking in saefal stLatLtitu auactaty with<br />
e hlqMer risk of Ivag carnaf ~•<br />
. 5) In the awrc thet *ha aawRr to tln .m q(aet(trts is afllrertive,<br />
d°°G the asappiatlca pgaLt after mRtollLq tor oeafpadiay<br />
'nriables7<br />
61 f5n a doae-reapenaa Eabeel psdw alnkiiq and lmrl er,orr<br />
be sMm in thts dan7<br />
. 71 An tlen diffefenx in risk for aiao ad .~7<br />
!1 Me there diff~ in risk for ae .er saqMrs ayd<br />
for fmier snokars7<br />
91 Is Lhere a higrer risk assoeiatdd Hrl+ a apecifie llnq<br />
tanaer histeloqit type?
2 SnARLS sl :e.<br />
_„_<br />
It ~ estiaated that a sample sire of 45o cases 1215 males and<br />
225 femlesl . tegeteMx with 450 ocntrols, wuld be eeou .ury to d7tect<br />
• relarive risk of the order r4ertsd by e1"'Os• 125) and<br />
'lYiMOpraailous, et. a1 . 127/ . prelimisary :nfacmtien ellectcd in the<br />
study area snv.ed that apureodrtately 1,200 femile lung ca,»tr ~<br />
aere diagrux.d in the study area every year . and tti: 9 .09 .exe mMrng<br />
never aroke_y, 'llsW, it ys estlaeted ttiat lallorini fur a 15%<br />
refuaal retel the 225 fnele eases coold be assenbled ln a<br />
:erial of<br />
a6wt IO noathe . rouyhly the tve available to collect the data for<br />
d :a study . SLMV oNy 2 .01 of aen .ere never sokers, garhe_-ing the<br />
ye~p IILLd,er of alate cases MWld have takefl rrlGh eY'xe tlae thM the<br />
available period alloyed . As iediwted a6~, it w suurlh a<br />
realstation that praped the de<br />
:isim to include cases that had<br />
sttigxd sidcing at least 10 years osek .<br />
1Le final saiple site fell slightly sheet of Ghe pxopeaed nuo~xc .<br />
tt vas caprised of the 439 taaes aed their 439 eetcned aentrols, for<br />
,AU;.h info[netioo ..s teipleoa . NRrq all eligible caxs thf respotie<br />
zte .es aose to 801 . SAccae.un9 an addltiaixl 4 .0% fa :<br />
drJ :icians* refusal to let their patients parti_ipate, the total<br />
rearanse rate o'n be estimted to he 759 .<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
) Im11TON OP STR SPDY .<br />
_3t_<br />
A check of the data acnnilatd by the tLV Ynrk State Tapr<br />
pegistry nloed t .4t abwK 800 of des of lug am.i ecwr aea,g<br />
residents of the el¢R Stantitd Metrcpolitan St .tistlnl Aress of<br />
lletate New York. 71fis loeale eoa4zisea 23 coaRies . with<br />
ap,wn.i .aely 125 diaqrastic ad/er trrnn
in<br />
-35-<br />
sussed by .the hveQtta!-oased r®ortu .q ays :es . Specal emphasis .as<br />
pat cy the field staf : an the tivelinns of the reporti.iq, lt+ce it<br />
.es necessary for tir_ p.ulmes of the study to aMain personnl<br />
iatervrn~ vi h the mxa before they died or 6eane too 111 to<br />
perticapate. The :~mn tiae elapsed 6etreer dia9nosis ani repnrtitg<br />
.as .3Geeted to be 45 days, with an additiorxl 102 days transpired<br />
before the e.xducttn4 of the interview .<br />
Rhe reqrcinq of a case .as follosed by the securing of the<br />
soksa9 histery statea in the pstiexs' Inepirnl medical rtmr.ls . a11<br />
wn reuo[ted as nevet sooke.7 . forvlr seokets or of uNawn smokinq<br />
stetm<br />
.ere oontacted by telaFMM and theix s .oking history<br />
coifiad . ohly those cmfitsed oever aekars, or ex-smdaexs for at<br />
:esse 10 yesn. .wte oansidead for itrcluslan in the study . Atl the<br />
eleqthility ctitezia for cases are listd i .ld.<br />
S fLOGG1811d1Y QtT1fRfA kall fA45 .<br />
1/ The patiwit aut be a resfdent of the 21 cuwit.y study<br />
area IS 46R of Vpstite Nnr York) .<br />
2) '17+e Patient had to be beo mm 20 ard 90 years of age .<br />
ll 7he patient had to be a never fsdoet lMrkM < . 100<br />
cigarettes in a lifetlael or an ax-spo'i (amted :dyvrdwl or a pnysician's muenat<br />
was not gnncc;l .
6 SF3fLTtaN OF WNmDIS-<br />
-3%-<br />
Lry order to pmvide a mme :isoa qrwP. each case ias<br />
irdiv/doally aerrhd to a PW+lacian aatrol<br />
. The aa+rce for soch<br />
coarzols ws fne State DeAarw'X of !btQ uMicles fiies . This<br />
source was cmidered apPopriate sinR it Pon"ided ~e of the<br />
rdoCnetion neoesary to perfara the aeecltLxl . Additiarully. thi s<br />
eethed .es re9asdad as :ess txw-comsumting and lore ecormirwl than<br />
otl+es Possible aeNni+ for the selecting of mncxols<br />
. such as random<br />
di~,t dialvq. For each aue. six potan:ial cosrsols .ere selected w<br />
c1e hasis ct age, an<br />
. and castty of rasidrsoa. Upoa a teled"<br />
lnterview, the tixst Pocartial control V .» was to+md also to mtc.h the<br />
case an tlr. bnsis of ssokvsl status - and Mn . in edtitiom, agreei<br />
to psit.icipate fully -was included in the study . In su,nery, the<br />
eligibility criteria for cartzols w as follous .<br />
11 The control had to be of the ssn+ aga l . - S yearsl as<br />
the cortesEa .vdin4 case .<br />
71 The control had to be of tJn ssm ses as the case .<br />
11 'Ihe control had to te a residmt of Me saae<br />
nmty as the mntrcl .<br />
Ii T.r . control dad to have the sare aaoking l+is :ory as the<br />
©se. That is, both had to oe eitle.r never smkers or<br />
ex-wo4ers for it lnast 1o yiars .<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
-38-<br />
An ad3itioeal artdiing variable was aaaidemf at the tiae of<br />
caducung the int.eview. it mcerns the aetter of +.hether t2e<br />
questiomaire was reslanded to by the case hiseelf/Msself or, on the<br />
other had by a*nrmgete fesPudent . The awtrlhing on type of<br />
vu:emer is better explaLal in the sectim of oRA CCLl2fia : etiieh<br />
apOSVs next on in this Qupcer.<br />
On the aa .rage, two Pctercial oo'xzols had to be ulled until me<br />
aetd+ed the mse an mddnq history and was rilling to partitipate in<br />
the stUAV .<br />
7 pNfq WyIffi'1W .<br />
Qae the eleqidility of eases and controls was determird . the<br />
Field sr .aff artanged a face to face intesvier vhleh took ap~tely<br />
one hoor to wnduct in the patiaR's hrnr . All rfaaatirn Was<br />
collected using a pre-oeded Gucstiosvaira, The queationnsire was Pre-<br />
tested for a 3 amth-period using patients diagnosed Pnnr to the<br />
study lariod . The sectiov of the qoestiornsire that coarutn the<br />
iteas used for analysis in the prerGit study are found in 11pPeMis A,<br />
AS wuld be siraecced, aoet of that questioro are orncerned with the<br />
measu,eer.nt of exeosore to pusive arcikinq ; but iKorsPtian an social .<br />
,Avo4rePhic and medical variables 'es also souqht . Both cases and<br />
mntrols were iirervie .ed exactly in the saae fsshiui, and eu.ept for<br />
cne ite :n in the questiuwlue reterring to the _ inical asoeets of
$~: ;,4a,=<<br />
_39-<br />
che arzre :r mafical cmditaa+ . they tcth av~red the sm.z nuimer and<br />
cype of Wesuons .<br />
tt,n the fie1L staff fwd that a mse had died or had be`'ane toa<br />
ill to pnrticipa2, he/she You1d ast to oaduct the inte :view r :fh a<br />
noa ot kin . [s-eferaSly _t' : the s^rane- but children and other<br />
relatives Nec'e also oonsidered apecppriate surmgace respo .imts . When<br />
a surrogate respordent had to be used for a tase . a surrogate<br />
renadent w also uxd for the crncml . tbr instanCS . :a,m the<br />
spooe of a case .as Mterviewed in lieo of the ase . we would seek to<br />
:r,cewiey the spouse of the persen aelecred as a ea :t_-ol,ol, err~ : if the<br />
latter .as available ad willing to be imervie.ed. In this respect<br />
.e should thn note chac cases am mnrols rera srtched 1n addition<br />
to SIX . 1Ge . 9rilIIt IRSrI)lC ad A6IDklL'CM on the TRE CF'<br />
ltffl7NIF11 conducted .<br />
0 elsmluar lesvra+ .<br />
M Udepa :da,t reviev of the patbology af.ednrns initially<br />
ezasinr] to aake the df.agnosis of l:mn eanzr s.sed uiportanc for :w<br />
reasons . First, to mske sea thst all ^ases weie ccnfirned priau'Y<br />
lung uncer cases . and semd . •a provide a unifans criterla of<br />
diagnns . '[be pceotdl•re fx wd : reviev w as follera .<br />
'.he ftel] steff .aIld Cx.ca .t rne pac.ieicgy depacaacac uf the<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
- .o-<br />
dieqrosusi hospirsls and ,.wld requ .sc the slides or tissue blodcs for<br />
the Patient in questiam . In all but five patav" socn reqest was<br />
sirasseaful . lfie *R-^ . . +..a. aould tlen be seat to a iLthologist at<br />
mmoriel Sloane Yetteritq Cancer Gs .ter in Ne.. York City, ao wuld<br />
revid Usa, blindly with rooard to endtSnq hiarory, the initial<br />
tuepital diagnosis, asd other risk factnrs . 'L1e reeiev pachologist<br />
assigned each case a hisruloqieal diagnr.is aa^oedinq to tne kbrld<br />
Neaith frganiatiof Intetnatienal Ptisroloqiml Classifiescion of<br />
'.lswra (B6) . lhe review dia.gnsis .rs tlen espared to the initial<br />
hospital diaspnais- if tlc^e yas dis+7caeKnt betv .een in:.cla1 acd<br />
cevaer diegnosis4 a seeord pstholoqist frim the saae lestitntim uould<br />
revlew the slidea artd assign the fiaal diaq :neis. E1a: trrough a<br />
detailed bistologiml classifiostlon w provided by the patLologists,<br />
for the purpxes of thrse stuy re hm uied a tarese elessifiewtion<br />
that divides our cases into the following histologic typss : f.pidernoW<br />
or squsnous tall a«ciflCff%, 9oa11 cell utciaaa . AdHmrclnars,<br />
Large cell cereLw,r. a:tl Others .<br />
9 DTOMt vMtlABfyS .<br />
:he aaie hy~is of the stndy .as cmrmed with the effects<br />
of passive sndcirq on luq c.noer risk . In order to assess the<br />
aaqnitude of such an a+sncattcn . .,e needed to have bath accuaate<br />
seasur'anents of sspowr.e to the suspected risk factor and accurate<br />
:roas.:rment of h disease status . Hov the latter w aCiewd nas
-a :-<br />
yee; e- .planed in the previous section dealing with hiv^-0loqic zeviev .<br />
ln r}us serSan it will be explained hou the expmre to r.he risk<br />
f .crjr was decemtined .<br />
9 .1 SR7U"P 9OILFC NA91TS .<br />
.t.as 59 to 73 in the :psstia ;:ai: _ IJppedis A) Lqo.red about<br />
w ~-g hao:ts of op to fwr spwses P.r study subject. 'met<br />
infornwuT .as used to aeare the follodnq eeesur~ents of<br />
asposore : 11MaOe_ oC e:wrettca asokid .~ b. rhe s(s . The<br />
mmber reported by the respendert rs take.i directly frvn the<br />
yuesCianaLre Lf Jw eue vsKecl 1ed hee; ar.:led only arce . or ii<br />
only me of his/lera spniwfs/ had sunk.d : If mre trin one s .rriage<br />
to a snoker wes reporrad . .Ae e+¢c~son w asefnered to be tfe nwsn<br />
naoer of ciprettes/day ssskad by as srrry spxaes as repocced<br />
Issinai 41 . 21Nnter ef Years tl±e s°ase smred . This fi9ire •w•,<br />
. tiken directly fras the rS»rtad mn6er of ye+o w fizst spuue<br />
Woked .ii.le inerriwd and livinq ta)erMz with the study .ubjeR .ws•n<br />
ap?licanle - tAat ss . in the ms, of sore cMn on sarriaqe to a<br />
anoker - the maeer of years ssoled by sulsewnt saodues rs s:nply<br />
added to che first figure. )17ota? nurter of cigarettes smked !Lrf•e<br />
ecane drinn ma .:iad life . 7tis variable .as calculated hy<br />
TAl :yplinq the mmte! ef cigarettes ssoY~d per day by 365 to ntu:n an<br />
estiswte of the +aoer of eigarettes seck .d in a lvr ; t .hen,<br />
nllitiPl,;InQ tlNt !i9Ufe Dy the n'1'r!t of vMrb the sDOWe W repQ!ed<br />
tG YYVe Sok ed in J! C1nrae of rlr .' :MCrN§t . WMJI af.re a1M CI*<br />
:pn.ue . .es :elar.as s+ sadcer, the ror.l arrried-life nuroer of<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
_42_<br />
cigerettes fa w3; .ould be adld into a single smasuremmt of<br />
ex,7os:a'e .<br />
9 .2 0Q'06tAE 1D PASSIVE Sflal
9 .1 PASi1VC SIqN1PG IN PcFAW4'tAa.<br />
The infe:eetion eolleeted thm~yh t~l! itee6 aGrked wyth an<br />
asterisk ir. paues 168 aId l09 of 7 ;Qeidix A'es the basis o^ `mich to<br />
estlsete eq.more irn the ruHiplaoe . This variable was created in<br />
nactly ire ssme nwmer as hanehold esEemue . 9nt is. the mnEer ef<br />
years tl,e atudy suoj+sc wrked in a lwrttcvlar place ys nultiplied<br />
by the eoi6er of sool-ers rie «orked in the same roon or arus. 2his<br />
was dme for the 12 anet recent jobs ud added ov.-c to ahtain a single<br />
rms:rmer:c of exposure . ?fie uMts of expcs,¢e . .as rell as hometnld<br />
vpnare, are eqaeseed in person/yeezsi aM their inte[laetation<br />
shwld also be similar : a smi~j• of epowue tot esch stdy subjee_<br />
to svakers in the %orlplaee ouer oerrtln period of tLse .<br />
9 .4 PASSIVE 9T71QNG IN 90CD1L CllaGIbT11NCs=, .<br />
Page No 173 in pppendi x A ahors the i tmr asked durinq th e<br />
interview in order to estimete ewposuce to secmdary sroke in social<br />
ctrasrtwKns .<br />
'Riee itmnt .ete iirceMed tc ml3eet iafarnetieo m J<br />
aspec.s of aynsum The ilLSC is the type of social acivitin .fiich<br />
are cmdncive to ex?Owre to psssivt smdLleg : secmdly, the frefi.rny<br />
vi`,.h rhieh fldi activities were carried ow' : alY1 tP1:Lly , t he stages<br />
in life (10 year ir.tervslsl in<br />
%hic h such ael vi<br />
ties were carrie d out<br />
• •Rie infernetion cahueyed by these<br />
n_1 _hat par-.icvlar f„eqoency .<br />
-_!e asoees o : +JGASYe •.e4 slrTeri^2 3 in a s ingle :idex<br />
chat uoee<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
e<br />
-„-<br />
fmn :ero to a rtvximan value of 96 . ',ftta indes is cbtainml by adiinq<br />
the infornetiun ooded in item+ 166-Z00M lbr further details cn the<br />
eestion of the iidot of eqmure the reed'r aet refer to the<br />
AppmdiX. 'CYreo bo[h the list of the att_`vities Lfcloded md the ,ay<br />
in Mudi the infomation w entered is self-eWlanetcry .<br />
10 tvmfIA1Ly CRaqRIDQ1G VANIAgt}.;.,<br />
Lupectim of the data sloed that .ases and coritznls uere<br />
diflerent vith ieqerd to vuiables `hitlh vere trelieved to affeci timg<br />
canos risk . It w dedded thet thM~e should 6e cauiMsed in the<br />
analysis as pn[wnlal Cmfouders. It .wre arre . M~ar, that the<br />
infonetian availa6le +.s rct of umforn quality aaass veriables .<br />
`neress infot21stian M sociodeMmraphie variablea was iiloely to be<br />
highly reliable . the infomatioe pertalni.q to drsycol and/or<br />
ott.uretional esposures - ail ebtaired on a s .lf-repoctad Esats -~as<br />
rot deemd so. 7tw . re nrried eot the adjtreme~t fa oonfoondirty<br />
var iables ln tro steps. 1he first, NLLd h ve call 'psctial'<br />
ad7osrnawt . ierluled oely those variaCles for whieh ,+e hsd •hud•<br />
intotrtntim . Such variables were RPLI(;tON ICathplio ~a Oflrr) .<br />
[KI7ME. N1RPW. s1a1CS Isingle verw ot'ri) . . !rd 42Bf7t ot' CIOVV.PItS<br />
sf10J/u9Y aeorq the fornrt smkers . In the secvM step tw<br />
veriables .eze added in order to orry oot a'full' dj,naeaot .<br />
otlrr<br />
'Ifine<br />
ver :abiea .en : en os,¢e to any of h C4HICJ,IS (never versLLS ever<br />
eqrasurel liated in itans t02-218 in paqe 176 of Appe,dix A , ard<br />
~ n to •R.`L . rt'SI OR RKIATILli CN l1E J®' Isee page 169 io
-a5-<br />
tnad :x A) . In adflitim to PJese . otMr relevaat varia6les ~re<br />
cvuidered for inclosim, hot a closer ammimum . of ttie :=<br />
distribution ar .vs) cases and mrr`sols slwed no simuficant<br />
diffelemcss. '.Tnse variaoles Kle : F]Wl1Rtl.'LV Dff= dR FJIli1LL .)^i:<br />
tilFS 1aQf 8Ug5, T/C7G6 t7R 1U18M : 17UO6LN6 TO A rAS MOLQIf;<br />
pAt .ro AT LLy£: rxMRE TO MEOS2E !1EP.TEFS : and M O6I7R . . 10 A 06V.<br />
dp Wpp $Stllri (paqes 169 and<br />
171 of AlpvidiII A) .<br />
Ye believe trst au best djnnted vtL:etes ~e those cbtained<br />
by rhe in-'-u+im of t<br />
.he first qraQ of variables, since they are based<br />
m the sret reliable inforsetam . In Me Mct chaprer, therefore, W<br />
mly preseet Lir. additia : to t2r eude e+*lizatma1 the results of the<br />
socalled 'Part'•lv ad7ustnant .<br />
11 AtalI15I5<br />
1Le e`nior of sutLstir,l amlysis terJniques rss primsrily<br />
determire.d by the design of the stssly . 1hs latter called for the use<br />
of terlniquea capable of aacou :ting for the srtOWsl, as .ell as for<br />
tec`.niy+:es capable of dealing .ntb canolex situations in wuch<br />
cv .araaces - in additian to the eq :osure verlables -- cnuld be taken<br />
ssultaneauly into ca+sideratim .<br />
3efore eVlaining amv f741y hae these technryves .ete eceLied .<br />
Lt is Rr .ineet to rmtim that sinpler tetlmiq~e '.ere a'so _veG to<br />
._r mpl :re :re :haracteristi6 of the data wlleaed. C:u.variace<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
-a6-<br />
swtistics aed/or sisgle frequencies .ere nhea :n. . : for al~t all of<br />
the variables for .R:ich ae had inforsettm . Such erplorarion of the<br />
data also iacluded -- ..hen eproppriete - the ose of etem and leaf<br />
or 6mo-ptot diegraee to m .e the nature of the distribirtim of<br />
the varia6les, in both cases and co :trols . Il :e crapernhility of these<br />
two qcapa also needed to be established and several sta~,ntiol tests<br />
.ere perforsed to such an erd . In the ee.e of the variables that had<br />
been used to perfcrm the art"'~ : ,4 IAiF. S7[ . 3pfTflC IQMIIIy .<br />
P6IDQ1M AMD TYPE OF INitRVIDi/, wa Imm+ of moca that no<br />
diffarersES ~e to be fosd . 9 :c there w no eertainty that cases<br />
and cTtmis .eold he equal in otlrz rv-Apeers. 5ociodmoaraprtic<br />
variv' les aoch as nw8er of ~s of snc=l attendsnam, kuaze, ethLLc<br />
gnKp . oweRry of origie. rncEer of times s.rrid. and othe-^s . .wre<br />
m:ns :ed osinq either paired t-tests fconti, ... . .s variaDlnl or ohi-<br />
sqi:ere tests Ifttlser's test for dlcnttsaoum vsria6les or chi-equsre<br />
for mteqcriml variables with sare than tuo lnalal . In the sene<br />
faelum thone varf .bles that r_te viewd as potential cconfowd'Ys .ere<br />
campsred first before deciding ylether or not to inclode thes as<br />
cv+fouders in tLe final ansly .is. IM : apptioble, th mmerisom of<br />
t.he petert .iaily m :faMieq v.riables +u done by treacinq the<br />
variables as horh ®teqorifal Ifor efolnole . yee/no euoaure to gas<br />
ccdu .?I and oas:irsoiu Ifor emmle . euo6sr of yesrs of empo,ure to<br />
gas .cdanvl . 'Rxu . the decision to include a variable as cmfovicer<br />
vas followed by the decisioe m .Aether to include it as a categorical<br />
or as a emK.inunus vnriable . tagartic regrenioo ss used to<br />
deternw:e if then w ev .denm to aswne linearity oa the effect of<br />
the ?oc.ncial xnfousfer . It my be useful to advance enw that we
U<br />
-47-<br />
of tLe pereatially eonfoudinq cmtsrwus variables (with the<br />
excepcion of inrae) sts..ed udiotioa of linearity . Therefore they<br />
wece inclad only as categoriol variables .<br />
11 .1 1DGiSllc .."FS• ESS:ON LCN lN141FD ONa-C4+lmL 57iNg5 .<br />
Iblfoxd et . al .. 187) have poblished a vethod to amlyre peirwise<br />
setrtwd stulies besed on the linesr logistic aulel destzibcd by<br />
cornfield et. al . (88) . As pointed aot by the aothnes . this method<br />
shws several features that p∎.ke it the 6est available cloice to<br />
analys data sets sudl as the prase:t me. Fitst, it allows os to<br />
obtain the estisate of efle.z tor me or acro e:qnsure variables while<br />
darntrollirq lQ variables not eaesiderd in the eatrfiifg . Semd . it<br />
tan ptovide estia .tes of the effect associated with different levels<br />
of oro or eo:e dtegorinl etpoeure variables, as well as the<br />
estieates of effeet for the levels (ooe uLLt cha'ye) of one cr eore<br />
cvr.Lsnos ex?ason variables . Nd third, it allows us easily to<br />
obtain estLiwtes usociwtad wdth the ditferent levels of the ewtching<br />
variables .<br />
In this adaotatioe of the loqirtic eodel the reqressor variables<br />
are represenud by the case-cs+trol differenexs of the valoe for dr.<br />
eR»sure lar cmloudinq) variables, the intercept is not :ncluded .<br />
ud ri :e respane is always pcsiti" IWt is, for each value o! the<br />
:e ;resss varu6le the:e is always :w case and one art .~l) . '1!x<br />
:ewltirq etltuietes are the naximsn caditic.el likelitmd .r..irtetes<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
of the pirmetrrs .<br />
In the rsesent analysis I u+d the proqra for lagistic<br />
re9ression available in CLW (99) . 7he analysis of eadl of the<br />
e,pm :ae variables proteeded very such in the aeee .ey. 7he<br />
follovuq . ttefefore . is a geeral deseiptim of the stapa tollowed<br />
to assess the effeet o! eaoA ot tllese e¢o .oe variables oa the risk<br />
of lt+g masr .<br />
11 .2 F76[StBE AS ^J1S430RL ."111 VM1AB[.IS .<br />
All infomatioe cn eeposure ..s mllecoed in wch a way as to<br />
al!or the ereatim of variables that .r>,1d reflect nd+ expoa :re in a<br />
ca:cfiuda srale. Me considered it usefol, horeeer, to look first at<br />
the effect of the espoeure veriatrles as ordinal Cataqories . fbr that<br />
catter all variables wse traneEoread into new ategoriwl variabin .<br />
U+e cx-off points fer the nteqorin Were chaen by following<br />
oarvention (e .g. p.cks of cigarettes/day) or by :aferrinq to Mnt<br />
ocher authors have used in their stw1~ !e .q . SYiclnloolous<br />
cateqCeisaticn of eWoeore to cigarettes in a lifetLee) . Once the<br />
categories had been created and the infornetiom mmewrited in tabMa,<br />
the analysis preceeded in this .ey :<br />
1) :Te eofel that assuies ro associatia: 6etYeea risk Eaetat ard<br />
disa+c .as fx_.td to the data . '~is is also referred to as the<br />
nadel with fa psraseters or the wodel of total synaetry .
-ar<br />
21 The Io9issSc aodel that considers expomae as an ordinal<br />
cateqorical variable w fitced to the data. These aodels<br />
provided esc.imetc of tife effect of each of the Lewis of<br />
eQImICe Yslnq Lero C1pML^e as the [e!ere11C^8 rJtH]oC( .<br />
31 In order to test for a lLr.ar trer.4 in the levels of the<br />
catcqory, a third eodsl as fitted . This inclVded as the<br />
reqressx veriabie the oasrca~tml dif`ere.oes cf the mid-points<br />
of the atavo
M<br />
ostegoraes .<br />
-51-<br />
At tus point it xas Also oanidere.i pe^anent to look at<br />
estineres for spaafie stratn of the studY FWulation<br />
.<br />
Peviaus<br />
srydin have sqgested that the effe¢ of psssive aukitg ney vary<br />
pet.een the acxs, or by type of interview or acosd£rvl to imu kiaq<br />
R; stor) .<br />
The ewtched design wald nat allo+ :zs to obtain estizetee<br />
for the zrin effects of such variables Iby desiqn .Aoee effects heve<br />
been set to be zerol . but eseintes for eacA of their leuels could<br />
provide useful ]nfornet:on oe the relatianhiP beneen the risk factor<br />
and the sady disease. Also, previoux -reseazch wrk has suq'lesrcd<br />
that passive saokinq soy daewmane the type of histoloqic twor<br />
.dereloceC by the pstiena . ltrreforew re wntd to see if the<br />
mqnitode or dizectioe of the effect varied aocudinq to the<br />
histnlagic type --mmside:-A .<br />
folla .s .<br />
Lf xrmwty, tie sOeA takel at tnis .raqe of tLe anslysis uere q<br />
1) A logistic eodel w fitted for each of the e>qxrsute<br />
variables . Tfine nodels p.wided escisntess of effect for the<br />
noosere in question, takLq into aQVm all 439 psira available<br />
for analysis .<br />
2) 5 loqiseac model uss f1etM for eaU of t .he ezcosue variables<br />
ard tleit interacclm with the nciahle TYPE af IICtP.V[fl+. l~<br />
ttese sodels es•..tsetes for effects wcre aMaind for Sf7.F-<br />
P15FQOfMfS and for SRIPACATE Pf57ONOfMfS .<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
3) A lapistie moiel .as fitted for exh of the<br />
emesure variables<br />
a.d thear i .» ... .e :oa vac : the vzzriable 4-ORZtL IQS.qtY. fY®<br />
these sodels senaraee est'ua ;rs .ere vlny ne d for<br />
t2VFA 3t/67B<br />
and Fvp{R sqlRpS .<br />
41 A Ioqistic raWel w fitted for . ech<br />
o f th e p___ variables<br />
and Ltiz i n2eraeeiama vith the variabl e<br />
umvided eatiewtes for F}f1A16 Md 17A= .<br />
g7c. T.eae mQ3els<br />
51 A laqietic arfel .as fitted for e .ch of the exposu¢e veriablas<br />
ard tAeir lntsssctions . .ith the varzable lR811II=e 1-!PC .<br />
FY?zrate effects WRre obtwlned for FpmfAlpID A!O 2Vyl . (la<br />
CMBqflNA aed 11DII{701AGTm At0 f71HERS .<br />
6) 'hsts of the siqnifian :.e of the effeRS of all of the ivNe<br />
PU'a"eterS Kra obralned . as weil as tests of the siqnifiau,,, uf<br />
the iotsscc;oas . 4he lattei are atIuivalait to testinq the null<br />
hYPotheis tnst the effect doea eot vary aa=yiry to the leuels<br />
of the st-Zatifyinq varf.zDle .<br />
)1 wre eaplex epdels iaelud'vg the eqOaure variable in<br />
questian aid tio . t.Rree aM four u.o-yy interactions .ere<br />
fitted .<br />
91 Models with L~le +r~ vanaqla attl all the hASible<br />
m~binatiau of Mrer .aY ieterectiqys .ete fittod .
-5]-<br />
91 Ftdels obtained in 8 ald 9 .rre oapnred to each oc•wr as nell<br />
as to rYe avMlest aodels obtained :n 1 rhWwgh S .<br />
10) fie • .ar_ables seleeted u poteeriai cmfounYss Wre<br />
included in r/w eodels cbtailnd in I uuough S .<br />
avkP2f]l I1Nf£<br />
11) A aingle eodel tlrt cmtu»ed the three mutuslly acluaive R!S[cfP3<br />
epan¢e vaciahlee Ilnuaehold . wftleca ard sccial esposurel and thhe co+taaxkrs<br />
.*s titted to the dete .<br />
12) A aadei wes fitted to the daG that caaK .ined only the tw<br />
variables with signifiaet effects eed the m+fouders .<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
This c`xpter is divided into three sect,icus . 1M tint is<br />
devoted to the desctiption af the study aaple !n terne of snHO-<br />
dmcgrapsic cl+atacteristio . in additinn. it dwzis tt : distriMnioo<br />
of the variables used to aatch oses to oorRtols and prneets the<br />
distrihution of casea regerdiey histologic diaqncaes . lhe sewd<br />
section easiivea the distribution of osstain variables not tskm into<br />
amount by the aistChiag ptaoen - variables wfLLdh . by their nature,<br />
n .y be cornidered as potential mnfoeders of the asaociatiee Eet+een<br />
pessi•.e saoking and lueq cancer (for exanple . pipe end cigar asukLngl .<br />
7hM! third aAd last aettloT la slbd(Yided into four auhsectSGtts . eadf<br />
ane reporting the aaseseaar, of the aseociation bet .Ken luq uooer<br />
aM a different neuurenent of e~aaure to pessivs wokiyr, .<br />
-54
1 DFSQII8f1rN OF THE 51UDy 'aM8[° AN)<br />
DISfM1IB/f10N OP 4EE l4.1C'_ItNO OkRIF&E+•<br />
The results peesented here are tweo on the stanstiul analysis<br />
prrforned on data petraiwn0 to 439 ose-ooDtn+l pai .n . Table No l<br />
preseMs thc sost relevant dcmaqtaPAtc checacte_-istio of the swdy<br />
suy7ects . By design li .e- eetthinql . the sez dat_-ieutitn Was set to<br />
6e aQproxiewtel•! euen . 1sts, there are 218 (49 .7%) feiwle case-<br />
cuntrol pairs and 221 (50 .31) pairs Of slos . in the saa aenner .<br />
.9e, whid+ .as eatmed aithin a .- five yec age rmqe . caused the<br />
nean age faz the uses 167 .05 years) to be very close to tfie sean age<br />
for tvrcrols (68 .13 years) . As is .ell knwn, scac lung cancer<br />
paieats aepLLre tL+ dLwsa later in life . This is likely to be a<br />
reflection either of a lonq latency paiod or Of tty requiremeot Of a<br />
peo ;onled esQesure to etioloyic factors necessary for the dewloFmmt<br />
of the eisesse) . ltaeouer, 776 Of wr a+e antrol-pairs remcted<br />
theselves 60 years or older at the tfne ot dingmsis . By the time<br />
the interviev vs -n"Ktr', an additional 3 .0 \ wre reryrted to<br />
fall into Vat cateqnry . 'tne latter lneeax .a. obvioosly due to the<br />
tLne elapsed Eetween the discharge disgnosis, tne obtaining of cotnent<br />
!ivn Lhe attrnditq Ghysician . tlle CVntactitq of the petient IWIr or<br />
he:sc_f s,d . finally, the er_anqement ard tsxductfng of the inserv :N .<br />
Siroe s.cv~%at snonq 1un7 calwer cases is k .v.e: _ohe poor, and sir.ce<br />
ouraw::q t!e infornetion d.recily fra the patient before death vss<br />
cros .°.ered ccicial for the qoality of ve data sotr5ht, ve sied to<br />
'aoncsas asd inrrr'liev as sbr_ as poss :ble .<br />
.ts a c~rsr,~-te . the sea+ o'xner of days t^d : tran
-57-<br />
crn_~ls . ltat pntienu r-*er.ed tlameelaa as !uv:ng been horn in the TAefS tb. I<br />
;pilred States (B86) . In adllttim to this awntry, 22 other<br />
NII[.VANf QLW)LTrR:4ff6 OF TlO: ST>Dy PCFt7ATIQ1<br />
cantri.es . smtly ILtvpenn . were sentioned as ?lace of birth . None of Si7C<br />
-5,-<br />
CASFS OOttf%ys<br />
tM differvms in the distrihution of ethnic grvo2 or national origin F991[L'^ 49 .7% 49 .7%<br />
lwIES $0.36 50 .3<br />
wne stacisticel :y signifrcer.t .<br />
qEa<br />
eQ•7f1 1[E 67 .05 68 .13<br />
I~ cties tl,, cv,tzols reeorted ever to havmq been mm~ried IN YPARS<br />
;87t ~rsus 9211 . Simi3arly . at tbe tiae of the inrt.rviev, fewer %upalc<br />
BISIORY •<br />
~ 160t) wie repcrted to be errned tron mr~ols . Mile these<br />
6EV6A 91Z a7L S 45 .06 45 .06<br />
ditfereaQs se sratvc:cally si.gnifiaunr (Qhiyyuare - 11 .46 . 1 dfl tuv4R Srplydt5 55 .1m 55 .06<br />
.he nu.bec of ti®s being wnrried or the eesn r.uK>•r of yevus duration<br />
1yP3 OF INIfliPIt71 •<br />
of aerriage .ere eot . Siqniflcant ditfeeerwxs of reliqion .ere offered<br />
b! the presenx of roro utholio (5AI amng tR cases t!+en aernq the<br />
ccntrols (62 .0 t), and by soze Prateetinn uaq the mntTol . (786)<br />
StLxRf'.,NJtDfYlS<br />
SJRR XTTE B6PQ€QAS<br />
611PtIC fitQlP<br />
67 .06<br />
33 .0%<br />
67 .06<br />
32 .31<br />
Han ascnq L1e ea+en (I28) (Qd-s*an - 17 .67 . 4 df) . Ilr» uts<br />
NW-W /I'"E<br />
t6=<br />
2.76<br />
86 .6\<br />
3 .66<br />
85 .66<br />
foud to be si9nifianty hfqher for the o .es t]rn for the m-tcol . .<br />
lftis lLdfrq suggests Urc aer.7Wq on canty of residence does mt<br />
senn effective to omxml for ~e status . Bwrtver, arochr<br />
variable . .hic+ is qenerally oonaidered to be an iLdimtx of<br />
xcioe:c statA , i .e . mn4ier of years of seiraol artendann , did<br />
IDUOKTIW<br />
MFJW MAefX OF Y%i0S<br />
OF 9CMf.<br />
A^RMHIF<br />
PV Lm OE BIBI11<br />
not stow any significant differences for cases and acntmis . '.`a ~ BFISOt@7<br />
Lt1Mf9 SW85<br />
dfl m<br />
11 . 4 12 .7<br />
non .r of ysara of xtwol ar_ers'anee tor caxs .es 11 .It vears ard, CA1fc4IC 54 .06 32 .4t<br />
Olln OR lQiE 46 .01 57 .6%<br />
;;.r cmtroar !2 .7 y'are .<br />
8I54OILTIC TYPE<br />
89 .7i<br />
10 .3%<br />
fPIDQeOID 50 .6t -<br />
'Ca distrib.nson of listolalic diaq'mes resulting fran the study TOEIJOGI .7[.:`{!01 25 .1% -<br />
1AKE My 10 .31 -<br />
reviev irdicares Wt Cie se;orlty of taees in ~ study ~e 9uW. Ct7 .1. 7 . :1 -<br />
7 ~ 6 .a1<br />
adenocariwos 1222 =ise .t . 50 .6!) : e;ider_vic ca•ciroro ccnataW.ed<br />
~~bc=h,.~g variables<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
86 .86<br />
13 .2%
-i9-<br />
aooot nne uu .uter cf the pacients 1110 caaes . 25 .11 . ; large ard small were sxtdied with controls .dn .+ere forner zoken . This ploeechire,<br />
cell acc.unted for e5 110 .Ja1 and 34 (/ .7f1 cases . rinally . 28 fnwever, did not neosarily ensure that the par .ic4larities of the<br />
patients .ae classified as 'nt7er' histologic types . I .e went to svcking habits of the forner smokers -- such ae intazity and<br />
gnohasize that this catego :iaatien of cases accarding to histologic duration of cigarette aoukirq - .,ere eoriparable asmg cases and<br />
d:acpmes is based an tne diagrnees provided by our sndy review,<br />
('xoept for the five cases in Mich the patLology slidn eoold not be<br />
obru+Kdl . 11" distriAorinn is very sieolat 70 the me derived fran<br />
the initial hospital dumnses . The ooerall a4ceen-st hets .een the<br />
latter aM our study teview wae 94 .04# with a Fappa value of 0 .564 .<br />
2 OLSet.'OVffON Q FGfRftUILY COt4
.6l_ .<br />
&M 99 coetrolsl . 7tre incenulty of this habit `as also similar for<br />
esse and controls (4 .6 ci9ars/daY (or cases snd 3 .4 cigars /day for<br />
controlsl . as w the overall length of use 120 .5 years tor ca .xs and<br />
16 .26 yeers for de cv+erolsf• Cases and omtxols wre aln siatlar<br />
in pscportim, iiKerity . and doration of pips smking . ¢tqthy three<br />
casn arrl 90 emttols . .ars ever pip smk¢s . The
- 63-<br />
,b 2 presen the t e.tiaat. ., eun dars .rrtr, o adds t,:iea and<br />
amfidmce lf .its for ..ch of tAess ospriscm . 'tlu ai9Mst rists-<br />
op.a. .7 torrspad to o6da rstios ot 2 .66 (for axposar to s[rasm<br />
s,,.d nq or .ore tz an ao agoaayf a+d 1 .23 tfor QxVOSUVR oeR..pmalav<br />
to 41 to 60 cLq.rettr/dsy) . 14e aar+spmdin4 4mntidaea limits.<br />
hpuaer, lodieW 6hat tlrss .nlus ate not siqnificrRly diffeart<br />
fro the mil .alm . iftiqi .ctdly . tltee af the aatia•tas in the<br />
table siqgaet a detaease in risk for 10011 tanac for tlsaa erpsad to<br />
1-20 dgaiettr/dry /CW .76971 . to i1-sp Mgaraetu/dsy IG6r.9G6J1 .<br />
and to 60 to s0 eiq~L/Asy (a1P- .6196) . 1.11awiss . tMa . •s•ima•'•<br />
aua aot afftastinlly diffetent ftaa the eell wtos. u slwt in the<br />
same trDle-<br />
a plot of tlr fiw tog adds eerrapadt+q to enc cate9ory is<br />
wodi in fiqure No l(est9aus rpns .ntad by dtands at eidpolnt of<br />
eaugary oalar) . rar of the points l.q9sat a patlHle 14wr<br />
retatiauhip . In ertl.r to tast tat 1Lrstity In th e o.t.qcria . tJr<br />
~.r.xnuol dUferwroaa oC the a W-poidt s of eadh ataqery wrrt<br />
sntered as the r.qr.aws vari.Etea In the toqistie eaMl . ' iM<br />
. .eJ..ts cetay.d for the +tap6 of the sitt.d line P. .t+.ae• .oo1oli ,<br />
wId t•st• .2271 1 ys not stattstiaslly differeit lrt. ssn . thanfare<br />
omcl .u1!nq t•at tlrt. 1s no widrwm to sUppnrt a 1L~wu rwpaw for<br />
the osqarin .<br />
2<br />
tern aap.r.d to a aodsl of toral tyvstry (G • 10 .29 . 11 df I<br />
- that is , to a aodel with ro psrARetersM rlrt aswaes no (W fe_re~ces<br />
in t>grnuaa for uass aM oontralt - neither t :+t toaal for ssFcau.-e<br />
2 -<br />
as r.teqoriea (G - S .JN, 6 df1 . ror !!r nndel for 13nsar tran: (G •<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
2<br />
10 .24, 10 dt ) . seaea to provue a better fit to the data 1 c . G•<br />
2<br />
4 .99, 5 df, aMaG • .G5, 1 df. respectively) . /lla.q the s .n lJtr s .<br />
a loqistic sdd that oapares zeto eipsoa " to any exposure 1•> I<br />
ci9/d+ryl aha .d ndtlrr aty sigqifican t affeet no< any apprap3ate fit<br />
2<br />
to the dara, aAen anpacd to the stltl with m Rramtters ( 4 G'<br />
2 .72, 2 dfl .<br />
'Ae analysis of the effect of maE .r of cigatettes/ day 8dnd by<br />
the sprue alw Lc1udM ter.tin9 the .xposiae as aa•••••+ n ••• tbr'<br />
thet pcpo.e a liir .r logistic sodsl .ns fitt.d to the data. 7he<br />
asds ntio as.ad,.td vit11the spars n dc(nq I padc of eigstaicW<br />
day . .s 1 .011 n.we xo . 3 . Its rJ6 mnfid ente li .dt, (n .6s6 -1 .1e)<br />
includn the null valua .d Mn.fate pevr}des ec eoidnas at a<br />
signifiont aesoclatitn with the tl.aly dlssew. It my be pertinent<br />
to menticn at this point N .t .M.n logistic enyr(sion ts applitl to<br />
ri. analytis ot od,ae,wa data, the e .tl,.te of effect a,t.urd for<br />
a parrlalar unit of axpnqure om 4 osad to olculat e the .ati .te<br />
as.ociated with other In+sls of aqcos.. [or iestawe, by .uttyptinq<br />
the e.tsa∎t e for 1 pae of eiy .e.et ..n+,y 10.0109981 by 2, 3 or 4 , ..<br />
wuld obrain the astUrtee of sffect as .oelat,ed with th. spw.e<br />
>,adrn the respective nu+bw of parxa /day. Ia ctie . .. e fashion .<br />
a:ltiPlyi ng Jie staMa .-d error of 1 6+dfPo.y by the quanticia cited<br />
atoae will yield the variation raoeiated ritA tAe'stissta at that<br />
level of Wposors . :t aeould be evideec by the yy in .WcA ch.e.<br />
utieetm sre olxalned that AiqMr .qmwrtes will alwys be associated<br />
with larger estlestas (as Mll as with qreatar variation) so that the<br />
.alsttcl ai9•.:fieante of the estiraites does rot vr/ accocdi q tn
lerel of e;¢rosura. 7n the praeeet enee . the estivntes fot 2 . J . and 4<br />
Tsd;s Cqatetoea/day wold all be rot signifiontly differa ;t [rm the<br />
null velue ; thair emfIdetumi intetvala rould facloda a .ri a a9ise .<br />
ligon tb I slnrf the 1ur that reFsuanes the retatianship 6etuea ;<br />
a;q orze Ici9aret!u/day in the X axis) ad risk of diaee.e (loq odie<br />
in t5o Y axis), ace Xdfn9 to the loqiaria eodel fitted to the data<br />
(oontlnudu lim) . Aqaln, the al.vR eKirely flat LMe auggeats a<br />
tarA of doae ie.po;w r.latimdup. 'On tro oMer It4rw rqz.aant tw<br />
su5geap of 9r study popolatim . 7he l.rye da.h lin annpmds to<br />
aekqfTTES<br />
NAT<br />
.Hf reapadw.t . . .d the uell dash line to aurragata re+pm8een, . 21- 40 - .TKM<br />
6nN of eFeae lime Yould ar to auyge .t .ffRa due m ewnwaa that<br />
are not only greater tlrn the effeR fet the 9it.q as a anle. 6ut 11-66<br />
also thK ao .a in opposite Aix+eclau fms oee anoUer . ilawuer,<br />
1-i6<br />
-ss<br />
TMIf 1h 2<br />
tNRMT[7<br />
.00606nTqdMp9ss CAlIppQ tlnm<br />
iq1 f]WO6UIIE to flTf GT[BRUfS6a0W[TTfy yfp p,ty<br />
, .Y10I(fp 6T TI( Xqff[(3) .<br />
f3TIfNTE SWUYIp (q m<br />
MTq<br />
%iLC 951 LY1<br />
-2361 .i566 .7H7 .6l19 107f7<br />
-966.7 -6666 1 .349?<br />
.20t1 . .3390 1. 2313 . 6336 2.3930<br />
nritibr is aiSnifiyRly dlff.n6t fraa the 1Lr that nprerenta all 61 -0 -.l6E4 .e7s1 .l196 .o75S z3322<br />
wo)MS, nor are they 6iynifionrly differa2 fr® ans a ;other .<br />
Lllaerise, the e.tL.tr that de .dbe these li ;rs am rot<br />
6ignifiwrtly dltfer.R flm the emll valoa .<br />
The lorr patt of Table lb l(li6n 1-91 aM liqie ;e Ib 2 . 3 . ard<br />
} . oreaent fer the 6t~dy pepulstia+ .atLww a/d fitted IL~'<br />
r.sµtt.ivaly . acvxdirg to 61[71QLS N1SR7RY . SOf and NESIQUJG:C<br />
olxtrJEIS . The aignifioaiw t..an ad ooifidera linls ir, the table<br />
etow no ei9n:fiomt effect of spaw Acly saokL;q .men eremined<br />
•eper.tely for rwu amk .rs and fara.r adara<br />
;re'r ;eea A:rtoloqie types . ualec ad famlesf ud epidernoid ard admee . M~r' t]r_<br />
tests of interaction of the w¢~ var iable with 9C1¢ :G IQS[CRY ,<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
ea . .<br />
1 .050 1 .1590 .2917 r.70'!0<br />
a
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R. .~' . .' 4 . .4 . . .!~ . . 4 4<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
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61911 fl6t' 6iS6' OY60' 0ibo'- 'naaf6v<br />
TO] 1TK<br />
t0lrr 6LSS ' LRt'1 YLfI' LS//• bplbi0idi<br />
i{i'tl tiii 6M1 o6Ct' IYKO' LiNM<br />
6COL1 116L' S{t6' 60DI' oC2Q• S1P/Yif<br />
L96T/ tL9Y' lLSO'I OWI' 9SSO'<br />
i?R'1 69W 6U6' ZOIt' YISO''<br />
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Zwo't LwS IISYL' f~St' Zorb'- liveass<br />
f6ff't YSZ6' 2511'1 1ri66 uot'<br />
st/nuoess<br />
l13S<br />
suwc<br />
01Y1'1 SS9P' tt161 9L6L0' %60t0' ttn<br />
0111M 1O6M3<br />
'CXI 146 ro1 fS6 S00) OM./iHtS 71ripK7 dUNU<br />
7bOlSIt13WODOL ~ WI]l7~S 7S(OdS<br />
0177YK9d)0 C 7YIlMIMLl10 V 1ql SL411XN7G{lQJOMI<br />
~SOIlY6S00i~S71YMISS)QilStYVMMI<br />
fqtIlOVl<br />
-G3
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http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
•<br />
f IaRE Nn 2<br />
CtNNCt IN IUND GNCER LDD ODDS WIIN NUIEER Q CIIMPEITES<br />
PER Du1Y YtOKED SY iK SPDUSE . FDR Il L SUEJECI S',<br />
NEYER Sr1dcENS' WD FCREtER SnOKERS' ;<br />
AM L00OD05 FOR Diff ERENE GIEDDRIES DF E%PU~''UREY<br />
' - - - --- .----- - - - - - - -<br />
•<br />
~<br />
as<br />
ctvwr •anv n .a.F<br />
Y cartl ~ . ..Ra`itN.a/<br />
LIM • Hr~ MaG!<br />
LAIiF-OAM LIM - s01Y[A GYIF1a OINOOY' YItrf01M OF Gl[Mi GLL W"lO<br />
f IDURE N2 3<br />
--<br />
- - - - - -<br />
-"----••-<br />
OWXE IN LI11/OCWELR LW DUDS WITN NNIEER Df CIWtETTES<br />
PER DAY SHCRED EY INE SPd15[, fpi ALL Si.EJECTY•<br />
FEMKES',AND hL4EY ;<br />
MD LDDUDUS FGIE DIFFERCNI UIEDOINES DF E]IPDSURE'<br />
-- _ ----- _ ___ - __ - ______ -<br />
• ~ r . r r Sr<br />
el(,ry,~T Y~EY[0 n ~R~Q<br />
aMll-MM LIM . I[YLL4<br />
UYLTWM LIM . YN!•<br />
•1/OA - Y/O-N1Ml CF UT[OdR NLL a/JRCt•/<br />
Ir<br />
m<br />
e
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
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AOJUf RD ESTIMi1TEl. mLS M1106.<br />
NC OdiID(KY IIMIiSrp1/1 arRNE1RVL G pt1OM TO<br />
SodISE 99UG166 20 CIOaETSE3/Mi .<br />
0R" E7I11MR JfA/6" 0007 96s lQ 952 04<br />
ENIi01 M710<br />
ALL -.0152 .00 .1I .90y .6369 1 . 1591<br />
as)Ecn<br />
41f .01]! .G9l7 I .0/7, .!9[2 1 .'J198 .<br />
Wspom,:<br />
•,7669 :lSES. .,6M6 .5601 1 . 0977<br />
~p -.06M .1271 .9A9 .7279 1 .19e I<br />
.0247 .1101 1 .02501 A261 0 .2718<br />
rOMlL7 -90P7 .1/0r .901 . .flq 1 .1703<br />
plun aa. .,tn. 1s'. . s,]! l3 .or<br />
~~ - .0! 1] .1337 .9719 .N71 1 .S21S<br />
awu au<br />
aA/or.. - .0,9t .Ilel M : :wt<br />
a onms
. .fY~+rYji ;~<br />
sec . u+o NtSIt4aGiC DtP[ZriS75 are not si9nifiunt<br />
. 1.•dinttoq th.t the<br />
estia.us for the -<br />
.o siub9raSM in asrfi of the rtrstifyinq variabla<br />
ere not siqnifi.xntly diffstent t :on or snot.hAsr.<br />
Able w 4 ptesants sst.isetn for ALL 611910Cf5 and for eadh<br />
level of the variables M6 DP IItIEAV1W<br />
. 9C!mC HL4m[b• 57c a .d<br />
lII51OtDG2C DLCWGIS ohtaind with the la ;L+tie :agression safel that<br />
iirluda omfavding variables<br />
. A coporison of these values uith<br />
ttae pre`ented in 7tible No 3 show aa aesnuqtol differvrcv . ~he<br />
tests of siqnifiacs MppoR the Ra+*M OosolosLSt of no<br />
siqnifirm associatien bst..an sxpoacre W etody disease . 'Dwn is<br />
also no evidenos of diffeawcr in tin lines zearemsntiiq the<br />
different sucqrrWS for rhit<br />
.i tlr affct of esposuce is being<br />
ewluatsd .<br />
3 .1 .2 N[lBFR aF yEVK Q' SPOM go= •<br />
M11n assssmm"t of yesrs of emposoCe to spuuse srokin9 as an<br />
ordinal eattgorial vsriable diM nnt slnn avSdrss of 4 sigmifit .nt<br />
sssodatioe with the susly diseaM (hble M 5) Al1 of the sic<br />
ertisrtn are aceonpuSed bqr test results that are mt statistically<br />
si9nificent<br />
. +s w+11 as by omfidprce 1Lits tlrt includs tir nd!<br />
vsloe . A plot nf the stiaato in yipes 14 . 3(dL.aM in .Id-point<br />
of otsrprias/ did rot suqqest s stron9 dss-rVOPmse relatiadMp<br />
pNer . 1fie ayuaioe of ncQ relatlanshlp %+s oanfinmd L .y ∎ nan-<br />
yylnifiaK test for the tr9msx amriabia ceposse+'1•+n a linoer<br />
trad for the acelfries (estmrte• - .00t93 . wid• - .a552! .<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
_7,_<br />
1M nuber of "srs of spo,w -!dn4 vs asrssa6 as a<br />
micincus van.ble 17sbla NW .61 it rsa fouM that 10 years of .pane<br />
sok109 W+s aa.ociatsd vith an adis rstio of 0 .99 (9S6 CLs 0 .912 -<br />
1 .074) . 0paa¢e to n sudh u S0 9yrs of apmne sm°kinl, rai9lay<br />
the highest eepusure obawa in teese aaa, aaua deesse the odle<br />
rstio to 0 .95 ( 951 6t .6200 - 1 .16001t 6ut aqaio, mia is not<br />
sr+ist+clly diffeteR tfiun the risk foc the nvwsesal . Also to<br />
7a61a tb 6 and in li9ures lao . 6-! . the sstfsetm snd fitt.d lines<br />
for the different levels of the motchiig variables aM the nn<br />
histologic types are lsaxnced . 'ss sisaq. the poiat estWtr for aWh<br />
of thse subgecips flumuce. IsoMeuts positiw aM eeqstiw values .<br />
Mhidh in ro case piess~c avidsnos of being significantly ditfennt<br />
frm tha udl valus . LUrMse• the asW .vs are eot slgdfiontly<br />
different betyeen tewis of the wriaEles St7I . 9p@1G MSlv[f ao0<br />
N1bT71a'IC DUQiM . as svLLwted by the lnterao[!al with the<br />
eTosors variable . Aa.wr. the Intseactinn tsn+rs~ the latTar rsl<br />
tYPS or 1N1tAVid w fosd to be sfqnifiea+t IIS .IA t.eo+ 2 .13 ).1 .96,<br />
p< .051 . so99sstie9 that the tlfJmstp fcr warvqsts relpmdsnts is<br />
differ.nt !tam that far rlf-raspaWnts . tbwetlrfas . as satlon.A<br />
ahor. . nsither on be aasidund to be si9fdfiont .<br />
the inelmfen of oenfasstLq wrfaplq in the Icgistie sndel<br />
ga+ezstd thr ertivistn preeenced in lebls lb 7 . An inspeetioe of<br />
these fiqures, for all ao6jects and by levels of the stratifyvg<br />
vsri .blee . wqcecs the oa"tlosiom mMytl by the imsdjusted<br />
astis.tr tirt th.em is ro a. .ectation with the sw9f diaeoe .<br />
JLLt.haqh this bssie tonrlosion is net c! .n0ed, it fhiuld te netal tMt
9f90•/ i6S9' 09%' Srm' 09V• r~ou~ov<br />
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i921'/ K0/',. iio0'1 09f0' tYOC.' ~p~<br />
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swtw coao'cuvwllst a3umaMn<br />
9A131W1<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
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fYZI'1 OWr' 00, 969i' 6COC- OZ-11<br />
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http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
F HM1RE Eb 5<br />
flKMII IHLUiUEWNXR 106QMlS WIfH NUH6ER OI YEMS<br />
TNE SPpJSC St1fXE0, FqRlIL SUSJECTS•,<br />
SELF VE5PONf1ENTS •, ND SIIRRCOVF RE :PdLEH17^ ;<br />
N/E1LOOOOOBFqIOtiFERENfG1E0UUE5trt EXPpSURE-<br />
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http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
FIOUAE Na 7<br />
ClW16E IN IUND CAIKER L00 ODDS WI1H NLRt6FR OF YEMS<br />
IEE SPOUSE SMOKED .FOR N.L SU6 .XC13•,<br />
FEESKES• .iWD IMLES• ;<br />
NfD LOD ODDS FOR OIFFERENI CATEOCRIES OF E%PDSURE•<br />
N• f a<br />
Malr / VIL/A !am nOaO<br />
• fbAtNJM LNg • 1LL U1Aw<br />
Y4LL4W Lfll • IdYll<br />
INO~AM L1M • WtU<br />
f1NO0 • YICAbiY 7 fAttOm GLL WRTO<br />
FIDURE Na S<br />
CHWO[ IN LUHD CMICtR L00 ODDS WITM M1n6ER OF YEMS<br />
TME $OCUSE 51'10¢ED, FORIIL SUBJECtS•,<br />
EPIOFAHC/O/3HN.L CLLL •, AND NfENCY'.NCINMV0INEA•;<br />
HISTOLCOICIYDES<br />
AiDL00ODDS FUI OlFFEAENT CA3EOORItS OF E7G0'L1RE•<br />
a a<br />
- - - - - - - - - - - - - - - -------------"'---<br />
_ .~ f. a<br />
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wiua .a LEr • Lslm .osa ro .uu ma<br />
LHQ~ Lu! •~ IWY a,0 t1+Ef L4LD<br />
OIM6O0 • N1pf6NR w tlifiplf L1LL MRC IP<br />
a
xw>:1 Jc 6Ras siY UT solmimpT> .1 . A4 Ass'• +vw= 0 : IoT'awpT aT 02<br />
1N01P iIM im YiaCG770 a(/. -a(Qvpp TO'aCbl'a0 Y A Twwi~<br />
lWTi ssn aacdt ap !q PrMms pqautbp le aa4vi0 Trmy s+1L<br />
' lsa . .i<br />
fE x sNp S9E xAsP/ssaa.r6p OL/ slTi LrTaaw raiVsi4 10 nnw «P<br />
.~ satiunbT2 000'OSL lano 00 PI aq Pi~ .Esp aad saiw++bTa io<br />
„ad T 7o aeloa e 0a srwlC SE &TmV pTaaw 7asFW ••aOUr+M a0l<br />
'ssaowatSts Twomm iiwsrtla7 ia7 uT a0u tp sasarw Y6TV •tlfiuryaas<br />
..wR anp pwoiys.w aq as0s iT 'a .nsroy 'ywba sTP To ssywa<br />
•va asiaaaa A- styc ' WO>smR )0 sP•3pffy w-P io asPao stE+ w<br />
saQSw a7 ao qm6Ti bmitow w{T, '&msc& . Io Wammwam T .4as<br />
sT" • owT 0n pIppe sm yaw aC9 ssan6H wp •aaoll Ow unp<br />
.apu sw .aaYl 31 'u0F7rnT9s4>•+ 3o s>
-„-<br />
.eron . The estimsces of the effects fo.r tne 5 osteqor_n asseseed are<br />
presented in Table Nn 8 . 1M fiat feur esefa.ras . mcealpsdirg to<br />
esposures of W to s00 .000 cigaretus, shw a r.g.ti.a sign,<br />
.q9eetin9 that the effects eey be as+r .rary to the hFpethnited .<br />
Vie.ed smttxlcally, Mw .er, elwe valuas are eot si9nifie .ncly<br />
d:fferent fran the reall wloe, as deedutxated by the m .fidenee<br />
iMa .vals alse prewiW fe ?aUle tb e. ".M fifth rr..finece,<br />
ex-eswdinq to m expowre of rore tirn 400 .000 cigerettes IOR =<br />
1 .0e61, fugyute a snll risk abov" the rid for the nm-expoeed . But<br />
aoaia, Cnis fi9urs does mt r..eR sratlsuol signifiearoe f95f<br />
CLt .6532 - 1 .6762) . The plot that presmts tha eatie .tes ef effeci<br />
for the fiee ate9oriee in a logaritlWC sraie (rl9ure tb 9 1 ngqests<br />
tlrt a test of linear tsad shwld b perforntl. TW p .vmfftsr<br />
representing this linear tred rs foud not to be signlt :rant .<br />
Ctaperfug the lo9istie ardai fcr espeswae as categuries a'd tie ondel<br />
for wtegezies as a linear vari+ble, with the mill eedel of no<br />
paraeeters (1 .e . total apmetry soldl, prwidd furtlrz evidence of<br />
no nw++ion between eoesce ud sndy disena. Mefther m.e d-vd<br />
2<br />
itself to fit the data better then the m111 .cAal (A C e 1 .95, 5 df .<br />
2<br />
and 4G - .0061, 1 dt, respectiaelyl .<br />
F]rposure, assestl es a eontimnos variable theaqh a logistic<br />
reqression eed.l, yieldeC ae esticete of effect equfvalent to sn oQis<br />
ratio cf 1 .0175 for eqnaue to 700 .000 riq6ratw dsing uarriad life<br />
( :bhle 40 .91 . This eeclmste ..s frnad not to be sfqnSficwt, ud. u<br />
avEaiued in a previms ssetian, iidlutes thtt ry estln .re for<br />
h :9her or lwer esTwaarp b .rd on the eres loqietic andel will be<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
f6A18ER0<br />
CIBWEETES<br />
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StICKED 6Y TNE SPOUSE DURIND PWIRIED IIFE, FOR ALL SUBJECTS•,<br />
NCYER StICRERS',Nq fCRMCR Stll.RERS• ;<br />
AID LDD ODDS FOR DIFFERCNF C4IEOCRIES If ExPOSUiE'<br />
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C/MNDE IN LUND%dICCR lOD DDDS WIfN NUt46CR CF CRNRETTES<br />
S17p(ED 6Y FNE SPOUSE OlMINO iW(RIED LIFE, FOR ALL SUd„[CiS',<br />
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AfOlbilOERf LIMITS iRl ADIA[AFMfUI pF pNf,W 70<br />
s7aA[ 970tl1e OI :00 .000 aOWrR:3<br />
6AOIIV ESTIMATE SrAWMO 000.•. 95l1a 9ssWl<br />
[NAOR IIAr10<br />
ALL<br />
SUAJIC73<br />
.0126 .0604 1.0129 .6662 1 .1666<br />
7[li I .0666 . .0641 1 .0926 .9170 1 .3019<br />
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- .1697 .155/ :6272 .{Oq7 1 .1224<br />
- .0212 .1226 .9790 .769f 12I50<br />
.0D62 .2460 1 .03" .6926 1 .6793<br />
1EM4t! LOl1 .104 1A067 dpj t7JS7<br />
wlllf .0216 Z11p IAQR AGy7 IffiM<br />
mw"W - .1R6 .1T39 .a7Tt s931 1./0/a<br />
stuL m>.<br />
"DVIOCA . - .0626 .2566 .9206 :5790 1 .46]6<br />
A Otltlp
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.qually ~ si9Nfiuot• Atso in Tahle Bo . 9 estimetes for the levels<br />
of the stratifytn9 variiCies 'fkPF OF 1NfElvfaf . 9O1@lG NI`1CAy. SFX<br />
and NISID11'Gi : DIH?14SI5 do nnt shw significant effects # aM in .11<br />
taseS the estlntp y .ra mt fasp to be significmely dltfennt<br />
rithln lewls of the ss va=iabl. . Inydditim to this e.cA of the<br />
oodels that irclUded the intarettlan Est.we.i the stratifying variables<br />
and 1r wVouure variable did not ptwids better fit to the dsta ttun<br />
the sodels for all soEjecta . or tMn the sodel of total rysnetry . M<br />
illmtsation of the lines fitted for all wbj.ets . alanq vith the<br />
levels of the stntifyinq v.rlables . is dame in ngutes 9 ttoi9h 12 .<br />
Finlly, the total t.>Ih~z of ciqu.tts s.nsed Oain9 sa_zi.d<br />
life ms orssed in the peawin of eantnudinq variabl" . Table 1b<br />
10 stw the estisrtu oEtainsl aed tM1eir mnfidsioe lisdts . In m<br />
ase did the pnsmce of ontaristr in the sadLL lsRoue the fit to<br />
the data cc omeil any st9olfiaM .ffact of the sspana. vsriable o0<br />
lotg o.noez risks .<br />
3.2 P765IV6 9CPHC IN 4fc 1Gf~,D<br />
Cases anA oa¢cols<br />
.are qiretinnrl ebwn: the ncaeet of<br />
a oken viEl vha they siesed their 12 woet -eoes: resaderes .<br />
tcyemer with the duntiT of .edi orhuDiTatim . The nu*er of<br />
sroken in eam hcuselold, multiplitl by the .srber of ye.a lived in<br />
aech purltalar lameeold, and suimed oe.r the 12 rnidtrras .<br />
estisetes -he nurCer of person/yean of eFamea to passive aKlkt :q .<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
I<br />
i<br />
-92-<br />
InspecUOn of the eav data .ho.nd that foc soie of the 12<br />
residcqes - perricularly those aeexapadynq to e .rly xms in<br />
life - the infornrtien on the mcirc of smoeea in the e"Unld . .s<br />
missinq . The data u.s analymf in -~o ..ys . each mkiyg a different<br />
assunption ahont t.he.e swinq aal.us . IMer the first asn .ption ..<br />
axwned that one smket had liwd in the Inu .etrolds for .ALdi<br />
infae.tim w .LLS.ing if, that is. thes. .s .videmn that the sprly<br />
sobject had lived in ptevicos or funae tsideas vlth at l .ast one<br />
other snoker . 0ifer aswaptian ese6er ero it . .s assuud that tlrte<br />
w no espaare li .. . . no .noeets in the tws .lnld/ for those<br />
residewes in rlLLae infotatim w sd»Lq . pyulta fra an.lninq<br />
the data urdet the two es .wpt(ons atm pratimlly idertiosl .<br />
tiwauet . 6oth seta of t+nln vill w tx'a ..nt.d w .llov the nrder to<br />
twke his/her om mrlusiau tagudUg the Nrdlf+y of Winfng values .<br />
39 .1 . PL9E .75 trtClA I1.91IPyiDN 1 .<br />
The resolts of analytleq Inueeold eqnnus u a ot .qorinl variable<br />
are sho.n in Tme tb. tt . Dzapt for tle ptyia. corerpadlnq to<br />
26-SD pereen/lvrs of apence taRe .91Sa . 9S9 Q.i .SS10 - 1 .S20t1, all<br />
point oas ratins svpest an ircteased risk of luq tanoer assoei .t.d<br />
with hcwenold esiaure to Passlue sTakioq. ftoun ~ only the highest<br />
esp,pce - onieh alao R'achws the IdqOut Miesra of .dfett --<br />
s1e+ .vidsnoa of statlstial siynifitsnoa /Drt far egoar to a17S<br />
Pn'sal/ye .rse 2 .tS (9S1 dS 1 .09 - 7 .12)) . 8ti1l, the plot of the<br />
eight estiman pteseiu .d in Pique tb 13 suygescs thet , li+nir endel<br />
snv be adnywte to b .¢ibe G1e s:r.ien~h{p oet. .c.n c5e rae>qal .a of
eQon¢e and the risk of diaease . In the usual ®nmr, a variable<br />
reflecti•'i lirearity in the levels of the categories (the oue•contzal<br />
differanca of the eidpcintf of the wteqoria/ ..s ancered in the<br />
reqmsion rodel . The resultinq aodel stwed oo be sigLLfioecly<br />
2<br />
dlfferer,t froa the eWel ntA eo par . .erera IpG • 9 .01, 1 df) . In<br />
additiae, the estimate reprsmtijq t!r slc0e for the fitra7 line ra<br />
foud m be eiqnilioetly different fcne sao lestLUt~ .B0W485,<br />
ruld• 2 .95 / . 4n omparisrn of the wedet for the oteguriea with the<br />
aodel for the 'liaeer' e•ta9orie did ncr provide eviden :e of<br />
2<br />
de0.raae frm linearity laG• 5.87, 7 dtl . A higher ocder model<br />
with a a wMio term rs fitted to the data blt it vas tomd ,nt to<br />
be si9nifice nt.<br />
:fie eodet fittad to the data m . .sue the effeet of o¢osore ae<br />
a oaK4uws variable yteldtl estlmet.s that suppart the aaistace of<br />
an asso:iatioe betre.n e>pewrte and stody disease . R1r odde ratio<br />
associated with 150 prmal/l9ars af e3pmee t .a 1 .856 . with lar.r<br />
(1 .218) nd ulper (2 .830) 951 omfidna limits .ell abore the nill<br />
.alue Ibee'lbblelb 121. '<br />
Osim the s.,e ecdel w ran estimate the odde ratio aesoniated<br />
wirh a very high epcase et 290 parson/yars o .arylnq bet.aen 1 .389<br />
aiH 5 .66, as indinced by Nr peitt eetlmaas ceefidon ce limits .<br />
Te effeet of !auehold smkiiq acxading to'fYPE OP I :VfHMFw<br />
d~ea nat 31nv di :hrences in •:1 effect for self-respaKimcs vers:r<br />
sur.cgate reepoMents ('YaCia Ni 131 . N.rarer . Men 9MaQ.vG iQ54IItY is<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
-9.-<br />
rn+siderd, the affecs fcr ,rwr .mlars is not eiqLLficant . +Mr.es<br />
the effect for fm.r s~olars ia . This filtlL.q is all the ecn*<br />
parlin9 because botb estie.tes are elroae identical in value erd<br />
heanx the test of 4^teuiT suggdts that they are nnr<br />
significantly differ .m fine eaeh other . ar effect for e.eh of the<br />
tw saae is also estieated to he very close to ene a,otlrr. in this<br />
ca.e, ho+e.iesa mrh are significant nd not differea frca eeU otlrr .<br />
A higher effect of hanalold ppive wdcin8 . .e foud as .oefated<br />
with epidemid aM .ell eetl hirtoloqie typa (ahx :e3) t.vn for<br />
edenacareinar aM other aell typs IOR-1 .621 . lkaeover, the effect<br />
for eplderaoid type is siynificane 1951 Q .: 1 .39-5 .76) . Mrraas tie<br />
effect for admoareinmr is ect (ri6 Q,r .435 - ] .{l1. Fi9um tb<br />
13 - 16 illwtrata the lines for the reqs+seion endela for rrh of LM<br />
sotq[ap de .eibed ahoue .<br />
The .odel that u.esees the effect of hauwhold e>qoaae in the<br />
prewrn.a of oa[omdinq variables yields rwlts that are diffecent<br />
ffaa the resulta of the rodel withent sarh variables (ifble tb 131 .<br />
'l1The estimate of effert for the Nole qrap is sllqrhly lowr lal •<br />
1 .S561, but eo clrrqe is o6 ..rid in its statistical siqni.fican. (9St<br />
Q . • 1 .0006 - 2 .42) . The aetlmat.s for slcroy.te r.apa,dw+rs, Mlf-<br />
resaonde,te, former sndrers, e.les . fem.las, and epidernoid hlstoloqic<br />
type - foraerly significant - do Bave oonfidwp intervals lin the<br />
Presao of eovariataal that include the eoll nlue, aM polnt<br />
estiaates M,ich suggest lener effec~s then the wdlosrcd eariaetee .<br />
Ihr point estiwte for adeieurrlhrns IpM .B7) . althwqh still lour
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FNRRUNn Is<br />
GMFqE IN LLRq CNfER L00 dD03 WITH PER701UTEARS OF E%POR/RE<br />
TO PtiSSIYE SF70[INO IN TNE NOUSfNOLO•, FOR ALL Sl16RCF3•,<br />
FEM6LES•,ND MI1ES- ;<br />
ANG LOOODDS FOI DIFFLRENI CATEOCRIES Of ERPOSIIRE•<br />
s s r n Ir Ls Ir sY.<br />
PYlql 1tY!{ V Oldw[<br />
lRafNb udr mf .ItPttm 1 . Sw lal br Add1.<br />
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M44af1 LIM • /L11t=<br />
lMf4~ llO • 11 .kU<br />
a .mas - .m+oln v uasaN uu Naano<br />
nDwt rd ls<br />
p WqE IN lUq CNXIR LOD ODDS WI IN PERSON/YFARS 0F E1/POSl1RE<br />
TO PASSIYE YIORINO IN TNE NWSEIQD•, Fp1 ML SIIOJECIY,<br />
EPIOER/1010/SW1Ll CELLN, MQAOENOGWCINOMUOTI[R• ;<br />
NISTttC01CTYPES<br />
AFD LOD 000! FOR DIFFERENT CATEOtlNES DF EXP64RIE•<br />
u. La<br />
Puei xw . mos~<br />
lRaulb iMr reumPHon 1 . S .e tal Rr df1Nb .<br />
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uros • .u+aln s uFCmn uu sane
-ICl-<br />
TMLE W IS<br />
-102-<br />
ttun the e.cimets for epideamid type ICR-2 .)21, t .kes on a haderline<br />
significant vnlue .<br />
Ap.SqTEDtSIIfM7EJ .D006MT106. ' 3 .2 .2 .7fS1R.75 @aFR A59t!@2TCR 2.<br />
A/O CNA;KX LIMtTSiOC A pfEEAEHNt OT f1VOIFE OF ,<br />
750 tLRS01V7FMlS3MOK1N017/ T/t /WSLMDID• ,<br />
GtpF ESTUNITF 57AeMpD 010% 95: lf1 95: La<br />
EQRON OATIO<br />
Nl .M22 .a'25S I6561 1.0006 2.1200<br />
5116BCiS<br />
St1f<br />
45PVC0119<br />
.323E ,2764 1 .3824 .A011 2.3766<br />
1Xn4eArt .6726 .3937 ' 1 .9593 .9056 42591<br />
sl7vcraen5<br />
NEM<br />
4TeA5<br />
fau<br />
1 smam<br />
.3753 .309b 1 .4354 .7936 2 .6665<br />
.51 S7 .3266 1 .6746 .6631 3,1764<br />
Rwip !Q79 ]256 IY71 .710 2AYt6<br />
nWS .El6 ]0Y0 139" ' A671 2l106<br />
9rwl taL<br />
W*"<br />
.M26 5M 2.3230 .67" 6.1996<br />
ADDIMA• 62!6 .3166 1 .6676 1 .0000 3 .4666<br />
i 9oOK<br />
anwurovsrr esrnAfai 1 . 5o iwi br eeen4<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
Table Iao 14 pre.'nta the results cf ansly-.inq handnld<br />
e:qnsora as a ategor:wl varl .Ele Nwl AwuetplA eWoaue w<br />
ulalsted under assuipdcn 2 . dcept fs tlr first tw .stimet'".<br />
all suggeat an t . . .on .. . .d risk for looq olner .mq G'r e:@o.d . Thu<br />
plot of the estisrtrs (Fig W 17 1 alsu ssso to soqqst tlrt tlb riak<br />
increases vith InQassinq empenur . MLLla nons of e!r aatic.ue is<br />
si9nifiant Isen oon[ideuoe 14db in the tabla, the lilrse treld is<br />
2<br />
f A G - 7 .014 . 1 df, goiiq f=ew the sod.l with no p.ra.etan to the<br />
nodel with the regressor reper .mrLg a linear trvd for tir<br />
cateqariesl . 41su . in oonprlson vlth she .rtla.tas oMained onder<br />
asseQUm 1, the pca.eet sstl.atas only differ te tte nor<br />
si9nifioules of the estirts for tLe hlqhest asponra . Yrn<br />
analyzed as a aonHnces variable 1labla tb 15 t!r ertlnrp of effett<br />
(Op- 1 .73 for 150 peraoNyears of efpekse) is sliqht2y lo ..r~thkn rh<br />
ef:eR obtained mder aseu%tim L (Un -1 .656) . Ik.e+er, tlsrir<br />
cmfidenes intervals overlap to a muiderWle de9ree 195% R : 1 .216 -<br />
2 .81 and 1 .137 - 2 .640 . nnpeCively/ . Slgnifiont effects .ere fooM<br />
for only two cf rhe s.*rouR an.lynedr for.er nmiaa (OR - 1 .770 .<br />
951 Q.: 1 .000! -] .1321 a:d .pidesnoid l.istoloqic type /OP - 2 .565,<br />
95% Q. : 301 - S .IT71 . Lcloslan of cwrtoadirq vsriahles in the sud .l<br />
17'eCle tlc 16 ) results ia ron-siqaicant affacts for tEa .e aM ti.<br />
er.'rr sobqisp . at %el : as for the qtap that co:SrSsee all suGj .r„a
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COWT q16' 9CYil tolC YDLC' C711N7f<br />
91CIT 9000'I WdL'1 016r LILS'<br />
9251'C I7A6' Y9C9'1 Z61C' 9m,<br />
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Sul ot6<br />
MAN<br />
C1Mi)nSY<br />
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Ollw EOtltl7<br />
TYI i96 711 fS6 5907 OLMXVtt 31Yt111S3 dflOUB<br />
o010N7ClIDI )11 41 Cat117qIJC CINJUNOCtlId OCI<br />
7D i1ffIS0At7 D M1N7N77110 Y tl0! S11NIl ZF1301lm01fV<br />
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http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
pnw loi uwl INS 'L Iq1101AO° +w~ clPoa6<br />
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YI aM 31CV1
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
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FNIURE ! 21<br />
DIMIOE IN LUND V111ELR Lb0 ODDS WItX PCR70NITEA45 K E%POSIIRE<br />
10 P/SSIYE Sf10KIH01N !HE WORP PUCE, Eq7 ALL SUtlJEC/S*,<br />
AND LOOOODS EOR DIE E~Nt CAEEOORIES K E YPOSVRE•<br />
-----------<br />
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http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
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wiLbAp LIM • ~It nlL~<br />
~-6W LIM . IIW ft~lP<br />
n .0on - aaroun r c.~ uu .auese<br />
PtQyB No . 22<br />
CFNNOE IN LI1N0 CN/QR L00 CDOS WITH PE RSCIUYEAR3 K E%POSIIRE<br />
10 PASSIYE Sttq(INO IN TI[ WptKPLI[£, Fqi I1L SUBJfC15•,<br />
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AIA LOO ODDS Fpl DIFPERENI GTEOORIES K E%POSt1RE4<br />
--------------------------<br />
J i • 1~ i~ f~1 1! 19~ i a s~<br />
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http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
L<br />
Ytal+6 Nv . 21<br />
DYIAEINLUHOGNCE0 .LE160DDSW1111 PERSON/YEARSCf FKPOSU0.E<br />
TO PASLVE NK,KIND IN THE WCAKPIICE, f0R rLL Slfi1ECTSY .<br />
FEMKES •, AND MLES• ;<br />
MO LOD ODOS Fp! Olf f ERENT GiE00N1ES Of EKPOSl1RE•<br />
. . . 1/ t/ Ii 7r 1Y{ i. a 291<br />
rvm ers r c.a~w<br />
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LJAft~ LIM . WIIi<br />
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C7N/M3E 1N LUd G1EICER L00 DODS W/TH PERSDN/YFMS OF EKPGStRE<br />
10 PtiSSIYE SMOKIND IN THE WORKPLMC f01t ALL SIIEJECTS•,<br />
EPIDERNOID/371ILL CELL• MID MENOCARCI11D14VO1HER• ;<br />
HISTOl001C TYPES<br />
AND LODODDS fOR DIFFERENT GTEODRIES ff EIIPOSIAL•<br />
w..... .q, .<br />
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ANOOONf10CN1I LIMITS f0A A OIffEqLNfY1t Oi E1fPo511AE ('l<br />
150 PEA :AiNfffA0.S MINB IN TNt WON¢PIILL<br />
IefRUfF STANONID 0005<br />
Bfqp 1 LAAOR PATIO<br />
951 L4<br />
95t Ud .<br />
ALL - .0101 .0106 .9900 .9797 1 .0107<br />
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~.1M7 .1395 .8657 .6N8 1 .1263<br />
-A900 .06716 .9159 .6017 1 .0175<br />
- .0081 .0104 .9919 .9719 1,0124<br />
f0Vlf8 -ABet A801 M3 J008 1 .120<br />
fWFS - .009a 4105 .9f06 .970I 1 .0113<br />
UVINSI'OD -„1 t 89 .0m .9M7 .9Q0 1 .0285<br />
OW :411.<br />
ANICU . - .011 S 0120 .9886 .9656 1 .0121<br />
1.071Eae<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
varsahle eui5oitn .he fiM :nqs desaiEed for t.hv categorical enca;ue<br />
variable . 7tie od'u ratio uaaciatd with an erpos¢e of 150<br />
1:ceoNyears w 0 .994 . vich loYSr /0 .971/ aM uppmr f1 .0111 95%<br />
ccn!idnioe limita that include the null veivc 1'fa0le No . 181 .<br />
ltreouer: omednntien ef . G'r .aNlwtu for the dtffexw)t aukqtcups<br />
defkKd by the levels of the stratifying variablu furrlar supPort the<br />
tark af evide+re for an asaooistlonflo~ patt of Table db le .M<br />
Pfqutea Ns I1.191 : Likevise, ••s--z = of the effart of espaure<br />
olttai)rd from soisls that Lcluie the oaKwMiny variabin du not<br />
providr erati.r+^ally siqnil'iomt esti .ap.s (7able No 19) .<br />
3 .4 E7ffC5UlE 10 PASSIVL 9UKfSIO IN<br />
SOCLIL CIDClS9C1lC8 .<br />
IYqht eategn•is mrzerfeMLg to d/tferant lwets of eeqroars<br />
to pwive snokin9 in aaeS .al setti+ga . .re capnd to aero e~wl¢e<br />
thrau9A the fitting of a logistic .odsl . ' 9xh a eodel previded a<br />
1<br />
better fit to the dan tlrn the eodet with nn Pen .eters t . 0 •<br />
26 .41, 8 df) . Tlr aatlwtas for the tw Iawt eMc.uns mrtenpad<br />
to odds ratios of 1 .836 and 1 .06/ t9aible No. 20) . 'i!e aqgestion of<br />
ilcreawl Ilsk for luq cwlar for thse oataqeryY ef arposure,<br />
hm.wr . is not supltorttl by the wide oontidenee ll .its ehat incltde<br />
tir nuil wlue. 7M six tawinlwg ueirLS of .Ef.rt - all non<br />
siqnifioent -- do taFw erptiw aelurr Wy alw .ses to Sidir~te a<br />
sttag linrr tred in that diteefiqn . tiqute No . 25 sfiurs':+r peints<br />
suggestive of such linear tred . A tert prtovided the neeessary<br />
sutistieal evidecs tescLrote •- .0276) . tald- - 4 .380) . Ll
-119-<br />
suns,ry, by =ittinq a loqlstie ro8r1 to tne data that incWdn<br />
eVosure as a cateqo:inl variable, we foud uo thieqs3 first . that<br />
tas resu 1tUy eotlel fits the Anta lecosr Wn a mMel with ro<br />
perrietats ( .uen tlias g h aer11 peiasetaar in the firol: mdd is mt<br />
siqnifiemtly diffetent fron rerol . and ssmd . tLat Mwt oetpedes<br />
are e.de to raI re.ent i+azwlnq Oa .es of agrsrtr . Mty sler a line.r<br />
tra,a o ppo,ite to that nypuetieai=ea . e.tiac u , a are :.ase in rialc nm<br />
i.K2% ∎.>n5 e PPO. Mre .<br />
^_Y analysis of the ildes of seeial e+@anaw to passice srakfng<br />
as a aoncin+ae variabiw doea not cAUqe the pitnas (4able No . 21) .<br />
Dposv¢e to 20 units of the itdex of social eqiostre is a2aipemiied<br />
by an odds ratio of 0 .699 1991 Cmfideioe ILdtsz 0 .5202 - .76901 .<br />
]he estlsetss Tar the different levels of the stratifying variables<br />
are all close to the value dtad abeua. with omtidmce limits equslly<br />
exelusiw of the null valo.. 0Kh of theae are shwn irn ti+e lwer<br />
pR of 11b1e No 21, nd Cr 1Las reprasentlnq the linesr trands<br />
aPl,ear In fxyur. . 2s ;ntwle 26 .<br />
Eurcneo 00 e, the imlosim of aonfasuny vart .blee in w andels<br />
fitted nave .e.y little lapact on tlr valt.s of tn, Polnt escia .tes<br />
( Tanle w . 22 ) . m. »a ilarlty of aajustee ana wwwa.d : .eim.re ie<br />
also ratlectid in ouerlappinq eonfitlente L>OCvals . Ln t*o Lutvvas,<br />
Iwver , tM 1^'*oS--+t^° of oonfaudi4y wirlables hsd the affeet of<br />
yletAinq mn-afgiEflom wstiseas . for aese9ate respuideme the<br />
cmfideice limits a .-o ad the o3L ratio (0 .951 ) inelude the null valoe<br />
10 .6424 - 1 .i261 . in Lhs swiw wy as do the owtfa4aitr_ ll amits for the<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
-t2o-<br />
TMIE th 20<br />
emrutta.cewluTro6r/o %s colrmfra EmlTs<br />
f00 Ey>'0511RE 10 EIOHl EkTE00RtE5Of iM1S9/YE SrkX1/6<br />
IN 30CU11 y17LLttWaS<br />
~ ESIfN1E t+~ OS<br />
fDRATIO<br />
952 lG %~<br />
1'le .6067 .6636 L6360 .33l1 9.9916<br />
11-20 .0617 ,66M 1 .0677 .t964 5.74169<br />
2t-36 -.1034 .607 .901! .t706 4.76N<br />
31-0 .,I94 .l63t .6p96 .1144 3.2606<br />
41-50 -s363 .es3s 30019 .107f s .I7n<br />
91-fa -xo6 sll" 6ofe .1112 33ow<br />
61-T6 - 1.aa 9sTl beo atu 13402<br />
70 . -1 .6700 I . 4SSO .1541 .0089 26693
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
f9Y1' 9UY 0119' OoRI' 9Z6~--<br />
aouos<br />
R~. t1R[<br />
0626' 616Y Y169' 9tilt' W9C- I ~totllpm•<br />
L066' INLG 66iL' WCt' i6tt• tT1V4<br />
ilit' 6Y91: 1ZI>: KYI' GW- St7NH1f<br />
00¢6' 6ZSS' 0/0L' OZ>•1' OISf'-<br />
19L1' OLIi' 969C' 1641' iZ94'-<br />
ommc<br />
laapj<br />
901E1i<br />
gnil/<br />
. :1looas111<br />
ZrYG BOYV 6" SY61' 9tiCi'- 2LVSOes<br />
illi' [66r' 4m, Oiil' 6196'-<br />
CSYL' ZOZ±' 0665' 0901' iLK'-<br />
{Og~aas7/<br />
NC<br />
Wave<br />
l,ry<br />
011Vtl Ki1119<br />
SYI ;S6 tIIRSS 9000 OL1qNlf 3lV4IL57 dlDw<br />
I OMIy[L/C 3LKLVJ'M7pCO1 ;IrIp6d10 tl 7ClfJ/l )4 hIS10Yl OZ<br />
l03MfR9df3 T WI :NIIfliJlO V!plS11N11 DN70IM OMf<br />
; 'OOI1Vtl900q'[Iri.itlfJ •<br />
IZ aM 31YV1<br />
N
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
.<br />
/<br />
. • r e ! r a<br />
i r• ~ 1 f! a a r? r a~<br />
I<br />
I<br />
2505521387<br />
r
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
-t2s-<br />
•<br />
a<br />
y<br />
.a<br />
~<br />
~<br />
j°ll<br />
~~~~ ~ 3<br />
1~ .<br />
~~Yd<br />
-t26-<br />
U6LL pa 22<br />
NOCOi~ ~LOIIM~ITSf1 AW altp10006[M1uVL~aFL919A[Oi<br />
20lMITSIIITIEIIOpIOFplp9p[7070CLLLP• 4L81p01!<br />
BRDA ESTIMATE STA/OtqO OOps %I td 952 OS<br />
[FPOI MTIO<br />
ALL -A6l/ .1107 .{264 .fO.H .7769<br />
SLILFrn<br />
SCif<br />
W90cm<br />
- .4616 .I3Gb .6176 .41763 .T979<br />
204"GAn -.0439 2034 .96i I .6424 1 .4259<br />
q[ssaoorn<br />
Wm<br />
glam<br />
rum"<br />
l+aaas<br />
-.6310 .1626 .6669 .4216 .6y6m<br />
-.1141 .1612 .660V• .4914 .I690<br />
rowa •aeo . .nhl aoa 311,111 .la .<br />
IM12f -]900 •Np6 .7416 mM .0!!0<br />
~~ -.3020 .2i16 .7393 .a603 1 .1676<br />
vWl Ok4<br />
^DOMA . - .3%3 .1445 ;726 .5070 .6926<br />
a mtas
-+n-<br />
esc:mert `or m*~Zuxoid licnlo9tc t)p.. dues tON ~ .7337 . 95%<br />
cmfiden
-129-<br />
ip,+eyer. he nnp!.e[ nature of Or Plcblw. iltlp with LY<br />
i<br />
.per!eecinn of present rewarch toolso have Preci .afN tne<br />
NublialsMnt of definite ttoclwions<br />
. As it is alaoat always ris!<br />
ose in epidemologic resesrch* it is the infc .setion fxout zwv k<br />
different studies that will pirwl& the evidecw neoessery eit[rr to<br />
rejeR er to sccept the esisteaae of the aeaaciatiou<br />
. The Presrnt<br />
,xudy ys car:ied out ra :attBer assess the reln.iWhiP bec-m<br />
passive smkitg arcl lug onR . as well as to ptovide aaf.ers to sarr.<br />
Of the seNndolegical Pmbleer ancamtend by other authxo . In this<br />
cMpter I will present a diac+rsian of the 9eoerel asPecv of the<br />
study that say have had an sffeet an our trmib, such as s'uPle size,<br />
omposltien of our sasly pepulation li.e . inclWion of both sexes,<br />
irclWion of foroer ssdelts. at:.l apPrerch to data aolle~tion.<br />
cinice Of statistivl taGniaues . ecd so an. M :s will be fellm.ed<br />
by a axr specific dlmasion of the results of each of wr expo .u.re<br />
wriables . faasing an the wsy in whlch tSwe results eaRoRre~ with<br />
others Praviwsly reported .<br />
7fis pevcit sddy is to deta t4t lar9sst awr mMceed m this<br />
suSjset . '9e aRliestiae of this fact refleRS an the ie0rcved<br />
statistical po~ of omr study eare otlrr studir with regard to tlei .-<br />
a6llity to detect diftaranas in risk 6et+wn the exposrd and the<br />
wieseoaed . 1twn the eatiwte of et4c : is aSpected to be rrxlerste or<br />
sss.l . as 1in hsen the osse as suqgutad by Previaus e9idlaioloqic ald<br />
laboratory studiesi coosideration of saqla sise takes on speriai<br />
isporeane. Our ast:mstion at sepla sira reqiured to Jetect an ef :e^<br />
of the order repor-ed ` .rrlependintly by '.lirrpo+ ard 'Cidn{uulou<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
-i3o-<br />
:esulted in a figure of I50 casc-catrol pairs. gira+ that a exrdhed<br />
design .ould be used . We .ere able co aseembla 439 pairs that net the<br />
eligibility criteria fully. A saeplc of this aiae peavides a a clase<br />
to 951 pro6sbility of oorrectly rejec-1ng the tmll hypoUesis Ipwer<br />
ala.lat.ivn hssed an an odda ratio of 2.01 p.uPOrt{on of exposed<br />
crntmis to spewe Wmkiog, P. of 0 .25; and siguitiranQ level, -[, of<br />
It has been sq9utM that the estSesrtes faud by 8lrayaaw, ad<br />
Tridcpaulaus are tee high, in light of what is Imoel a6w.z smNe<br />
uQUke by rm-*ukers (the uptake has been estiatad to be aluivalwrt<br />
to the amokitg of 0 .1 to 1.0, oiqarette Psr day (451) . It fo? laa that<br />
the use of suoti estiswtp tould ousrestS"ta the pxr of acy givan<br />
sanple sin. An odds ratio of 1.3 is hliavad to raflacz son<br />
acauately the risk aswciated with the lewl of wpenue attained by<br />
Passiw smdcicg 1651 . Mle rs ur the latter asriaste to calculate<br />
the statistiol Porr of our sWPla ais, the resulting figure is<br />
er111 higher than the cvnrntion.l3y aaaeptad Ws. tueilreMre, yrn<br />
in : tlrse ealculatiqu .w ohuge the value of the Ptaportion of the<br />
eposaS epKtuls from 0 .25 to 0.50 Itlr peoportion of aqwsad cmtrols<br />
actually ebsarw0 in our studyl . aur sratisttpl Poyr Lnaesses a6eve<br />
90s .<br />
The difficulty In gathering a large enwqh nuter of cases for<br />
study derives tran the fact that nnnt l .ng oaoar asea occur aeang<br />
sackwrs . tlron thoialh the latter are proosnly expcaad to large aonu.¢s<br />
Of emiravrcmal toeecto sedce as a cvuaqueev.r of both their O~.n<br />
aimking and '7air assoclaucn with r_'*_- srtokcs, t,ey are avurted
-131-<br />
for a study of the effects of passive ssokinq. since tAeir o.e habits<br />
wold tend to eeek any effect due to ervirvneatal sadoe . w<br />
rexgnited that the ideal erwp to be .todiad w a gzoup of ne~<br />
ssoiaexs . It Oeraee avideerc . Fv.ever, that tne pcpulation we rere<br />
werkin9 with waLLd not yield anaqh navar sndtiaq cases in any<br />
Qraccial period of tim . Instead of red,.zinq oar seeQle eize at the<br />
4Werae of statistial paer. it ras dacided to include ex-mmlaers in<br />
the study . 'IDe a+jor prespectiva studies f90-911 have shoyn that the<br />
tisk of lurl cenaer aonq foner su.en can daQense. after 15 to 20<br />
years, to a point sMra it eaerbles the risk of the never .edoen .<br />
a the awrqe thaa-rohsrs Litludad fn oir aaiple had qoit le<br />
yesre prior to thafr lnrticipKion in w sdary .<br />
. ur em ayre,nonetlrless,<br />
that .or raaidial effea of past sndcinq habits ai9ht<br />
still slnw in atr data ud this oonfovd the etfrr- doa to pusive<br />
we cmk threa sapa to enan that oot coselusions veuld nnt be<br />
affeeud by the inclwian of fateer sanMrs . These ane 1) the design<br />
of H+e snudy esraklishd tlrt asas and costols should be setdasf on<br />
tha basis of . .okinq history. 21 sepsnte eatLrtes of effect vera<br />
obtained for asckers a.d fomes ackars, aM 31 We aonttol7.ed in tlro<br />
anslysis for a variable that represented the ne6er of cigarettes the<br />
ex-yndeers used to ada p's day . Oor CeaWts prM".ded evidence that<br />
the Lnel•~sion of Lomer ssWaers was not i'rppsafdau . In no asa did<br />
w f :nd differTCes in t.4e estinates of effect beaeen n.ver and<br />
fotser mokefs Msich .efe aptistically slqniL'.car.l . lbvere'rless . a<br />
:esidul .e!!!^ dus to past Y(awing haolts yas tou4 . ?bcrcr aTrJfeis<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
of I ps* of cigarrsew)day rtnrd a statistiolly significant odds<br />
ratio of 1 .30 . It shcold be anFhssised th .t thie effect w.s<br />
cantrolled for in the analysis lea asalained in nudrr 3 . ahaa/ and<br />
therefore is nar to 4 viasd u resporuible for amy effect foad Lor<br />
passive aakin9<br />
1rnt twsiecLas hsw raR[ic4d their sbHis en passive s a kinq<br />
aeluaiwly to w4so. 'Rhis is again related to the fact t1Ht it is<br />
enier to find non-.uking lvq viwr tases aeoy •tmen than mansl<br />
sea . In this Cnin it is iaiplisd to a certain e¢at tlrt results on<br />
tlen be estrapolatad to swn. That i ., lt is aseiasf that own are as<br />
susce ptihle to emiva imental nuka aO wuen, althaqh this is nnt as<br />
easily obetved in a ar/e popolatlin Eeeauaa nsn acquite lung csnwr<br />
ss a mnw,7oe M of their own WdHng . IKIe this prepositicn aeias<br />
sense, ee felt that it de.etv.d to be eusluatd . The findinq ot an<br />
association in srles awid struqthen the evidence of the c.rcinoqaMc<br />
effect of envitomsnc .l sncke. Pa stiNy includes also the largest<br />
Series of n .le nm-m okiig lunq tannr osea 126 .SS of these are<br />
never ~alata .nd 71 .3% an fonrr asnkers/ .<br />
Oor cases •ere drmn fto∎ all di.qnostic ad tmsaes,t facilities<br />
opentinq in the study area . ftrther aierJn for cases .qza perforred<br />
at the t+w yerk State 'Mor 8egistry . bsNpt for a fw cases dq ney<br />
iave left the ares in order to 9a•. erdial ora in other reqioin. w<br />
are centident of fuving detected .11 inddent mses ocarrin9 during<br />
t!e study period . Oot rescnw rate of 161 ean be oarjideral 9ca1 fer<br />
m+t es+umtion .l sWdarls . t+e do net have deu/ . :ed in'or»dciae on
-133-<br />
the r.Mrac~risrio of tne in0ivWnels .rtw refumd to parti='pate . but<br />
it is the luPreessicn of the field rt'swrch ausisear .eS that the reasans<br />
for refusal rere erre of a sedleal neore - i .e . Cie oase ws taa<br />
i11 ro Parric<br />
.pete - aathsr then eesodated with aey Pu'ticvlar<br />
sxiodemqrmnrc cha=ae'2riseica .<br />
Corect clessitiwtim of tb stedy aubjeots atxozdi^4 to their<br />
snkiag Aisemy is encial in sntliu m Pa+siw .roki+y. Inclmion<br />
of os.zant lalars .wEd epaiowly i'ievase the ci+k for the study<br />
dseaee . wen a,ckiny status of the rapated ^-axes ..a aeoertairod<br />
as paet ot dexeminin9 alegibillty for ParticiFatien in our study,<br />
aelv r8ase repoat.et in clr .dical raesda as formr smkers, rover<br />
adrrrs at of aYec .n snakle9 sntus nere oontactad by teleptea+e to<br />
!=ther ca,lirs ttar .mkinq hfstoties . In addition to this . the<br />
resesrEh assistant vaild at the tler of the int .rvlar further quesrioe<br />
G+iesa aobjects in this raqaA<br />
. Vr nad to emfia the smkLq<br />
hlsrnry sruted in eslinl remrda is 6at illost :ar+d by Cwrtinksl's<br />
fLdinqs (301 . In that study close to 40% of rhe wron with U.g<br />
cantar elassified as narsmlaa (or mkU9 atatw rot stated) an the<br />
la ;spiul noorde, had peen snirrs at a .ae tLer. In our study no<br />
a:-aept .as aade to confira the aoklno history of tlc.e reported as<br />
sokars . or even to establish tsn'act with thus. !t seero tese<br />
likaly . haraer, wt a foner or a neuer .roker wuld reporr<br />
tdaAhverself as a rorzent sokar . rhu aeaPlnl incluaioo into the<br />
ec av .<br />
lta clcoe swtiny of oir eues and cartrols regaidi+g ehei .-<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
i<br />
-13t+<br />
udkug luararief stroqiy fn'imres that misclassiftcat :m wes nct a<br />
Lilxly av .nt . Pravious fadin have beea µestlard ia this regard .<br />
aie ralatiw:y high lael rnwr eomality aee .q mramokLy .a.n ae<br />
wpnd to mockitg .a.e in tllraynr's sbcy t251 . a+ .+11 as the<br />
hiqh rintility for other G*attvr+lated diraw . hve nq9esud that<br />
sos w#inq ymen say Irw reparted T1rMlvet to ralonq to the nvr<br />
emckirp qso.p . This would not be eurpriaing in a traditla+al society<br />
suoh as Sapeo. The aoesaqsaas of euot. Wiaclassifiestinn vnuld be to<br />
ouetMCiate the sffat dir to pWivs aecking .<br />
Sfn Oreek stvdt (]7) on al .n Lr crit/eird on the saee qtoaxla .<br />
120 cla1L that arta tha 731 140 odt of !11 of lag osnoer ouea ..re<br />
diagnosed aecrg nor W akbg WOOrl is incasisant with the propecttee<br />
reporred in the liteature . It is mnfdurd that only atoK 10% a[<br />
all lag rarcer in woi m onuts in narma da_-a , (tee aa[rapuding<br />
tiqure for e .n is 2 .0l1/ . It is tfrtrfor" litely that this study<br />
wntoaded the afGte of puetw sdNnq with elr effect An to direct<br />
ci9srette .nkiig . at leat to a ontaLn degree .<br />
8efors oa study. only tiarfiNUl aM caak.rs (30) Atl carried<br />
out an indepe .t .nt review of the histologic diagnoses of vaes . In<br />
snst other retorss the auC'ors wd relied oe the dischergs dta9no .aa<br />
reoorded in the patient's ndicsl nooeds . The deyree to .hith rlow<br />
diaqrous wwre hased oe woskrtim of pathology epecisms is wrid .<br />
In Tridrpcuicuf' stvdy only 351 Ird an histnloqic diaqrrsie (271 .<br />
'11e casespondinq tiqen for nkiba's stuily . is S71 (321 . Pelayo Csree<br />
relnrt. 9'71 (29) . Oorh Nirayaw 1 work aM 6arf itdn6l "a f irst study
osinq the w'erian 5near<br />
-13s-<br />
.e,mety data rwlied sxelusively oc deaLY<br />
osrtifioto 121-231 . The isportarca of histolnqic die? :«ses is that<br />
it provides the soet amtt.ta smsurenmt of disease status .<br />
Inclusim of other onocs can Wes the rssults either a+y frtm or<br />
tw[ds tle null value , de{andfoq on saerliec or :at they are related<br />
to sycur) . T .e latter ts tBe eost likely s[tu.ti.en since inclusion of<br />
orher arars .culd tnd to be ssndas. As .dditlonsl adven
-137-<br />
diffetenteet eusclassificat_an in o.r st:dy, we ,wld cveet to f>td<br />
bias elG'Mt aMy froA Or tdYids the plLl ValOe . If . oIl the other<br />
hand . av :u:fferrntial elsclassifiration atfecred onr resolts, the blss<br />
m,ild omly he an attarr.ation of the .stisatn of .effectf far sC :<br />
m:t.inwsly awsord variables as the aras asaessed in this atvdy,<br />
the segtitode of this bias wonid depe :d an the ragnivde of the<br />
correlatian beosn tne tn:e values for etpo .ure aM the valms of<br />
e%PCPre as MWred .<br />
We did not obtain infcmacian On c ertaio variahles km .n to<br />
affaat aa:aw :re . tMStilatim. eisa of coms , pea:imity to the amlmr<br />
a::d other to:ditlons onder M:ieh suklnq taku Plaoe influere the<br />
aocoal doea reeeiwd by the pssiw srolor . Ne atlknwlabge the<br />
diffiwlty in obreirtng d .ta in t.41s raqard, eqacially if irQonation<br />
a6ort a lifetise is tewt souqht . Ma also beleived that askinq for<br />
s :d : ezcee .iw derail in a :, mestiornlre might peeaent our aoqoisitia+<br />
of aar basic irSCCeetlae. Ly distracting the intetvie~ froe<br />
eseentials . Bw t .hese facters say haw influe:ad nur results can not<br />
finally be datw omfned .<br />
Al I o :r omtrols eaee ftm the files of ttr l1n York State<br />
oepareaent of ltwcx velLLclu. M h" .deta to support that they an<br />
caq:eraEle to the msn in tM ooat relew:t ctrraeteriatica . 'Mece<br />
is, h~ . ons potee:tial soorea af pecblv . tt+ereas .e an<br />
CWMia . M. definitioo . thst atl oa.tsols rere lio.n.d drivara, ye do<br />
not kro+ the raxs' staws ,.ithtaqord w dri•Mq . If driving statu+<br />
ls sa:e .tior related to the tisk of 11319 oinoer either directly or . m,ch<br />
.more lue7y, u,C_rly . aor results might haw been soClece to ~ias .<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
I<br />
Na+ewr . !f any poss/ble differences tn drivlrp .eatoa reflect «:ly<br />
differences in aoeioeco :o.te status .our oo:2rol1Ls1 in the analysis<br />
by IHm4E slnuld have taken eaa of the paobls .<br />
Of all the eun¢as aiml to aeaus eqoeore to passive aiWnq .<br />
•me .m .uis,ee: of the apnue achirg hebits has he.n the mst<br />
frequently used . Thia sy .caastt.at least {aftialiy, for tne faez<br />
that Lhis if also t3r a.. .ure .oet otb .: rapccr.d to slew a positive<br />
aaaociatue with luq oncar risk . Iuanq the dUferent wya in MLLCh<br />
spouse smekinq has ber: quantifid, the ms6er of eiqacettr amaroed<br />
p.r day alpa .rs eott often in tlr literature . Nabr of pads a year<br />
xoFed . total nue6er ot ciqatKtss ad:d in a ilfatim, nsEer of<br />
years snddnq, aod mabr of tiqatsttr smlml at haee havw also bm<br />
used n a ptosy for esprs:¢e to passive .nkLg . In the prw :t study<br />
we haw eho.en Mr.e different saars.nrs of eq+oson: 11 :snhr of<br />
eiqarettea saaksd a day by tM al+o:w . 21 :snEar of yaan the srou.e<br />
snoiced. aM 71 total tumber of aiqaettes edud M :ils wmrriad ad<br />
livinq toqetlrr . we pelidvs tiras tlrc.a s.esuraasnts ao :prise<br />
inforn .tim an the t.o snst Utnrtant dlsansio:u of axOmon,<br />
intensity a:d dration. Mditiwly they also prwlde reaolts easily<br />
oaeperabte to those in otMr statiu .<br />
vreviaus studtu have shoun that nae-rid :Lq ..ar: ar-id to<br />
st.ti:ers of 20 or sm cigarettes a day nAlbit a risk of dewlopinq<br />
t•.ng cancer that is aq0eteda+taty double the riak of tlose satritl to<br />
mn-smtrers 125 .17 .301 . The btlsates obtaind in those Kodias hne<br />
bew: :eported to be significant, and .ti.: m:sidezed along virh t!x
-1/9-<br />
e.eimn:es for achPr levela u[ a4aw[e, t~ also mm foiad to siw a<br />
doee-respmse re ;atlo1uhia. %akiC+ further svppozn the mte for a<br />
ar .5a1 relatians,hip . fbr a so.e.iat ccsparable level of exposure .e<br />
.tre unable to detwct aay significant in¢esse in lmq orcer risk .<br />
Occ point estimte of effar- fQ those individuals married to wakers<br />
of 21-40 ciqarettesJday .na an adds rat .'o of 0 .906 (959 ¢ :<br />
.609-<br />
1 .35) . ~ exposure uss malyred as a atsgrical var~-ahle . For<br />
ntqtur levels of exposure .e fourd risks ahnue the aoll valoe . aut<br />
aa. .• ttese fiidiags were aot statiatiolly signifia,t . '_M analysis<br />
of exposure data as a apRi : .cus variable w mnsistant with the<br />
ahoee -m .ultss inleed the effect twrl fQ a differential of exposure<br />
of 20 e[9arerves per day rs hstely abave t1r iuil value (OR • 1 .01I),<br />
with c+anfidenee limits that include sueh a fiqure- !mr tMre w aay<br />
evlderaae of a liroar trend .<br />
9hiL report is ent tin anly a,r that has bssn unsble to onnfism a<br />
statistically signiffont as.nefatLon htsn nu~er of cigarettes<br />
.ukad by the spase od lnq anoer risks . Akie., at . a1 .(32)<br />
reported an adds ratio of 1 .31 (909 O., 0.M-3 .171 far LSare .,paseA<br />
to spsoe mekleq aS 20-40 ciqeratees/day (reported as 140-279<br />
ciqarattes/umk) . fbr a s.fnllar leral of eaposure, hlaqer at . al .<br />
(331 found an adds ratio of : .3 (95% CLs 0 .8-2.7) . 8rse latter<br />
estisatae . alrlooqA not signifiwnt, are within the r+b'qe of the<br />
suspeetd mbqniCAe of effact . A closer fi9ure to as re .ulta,<br />
haever . w reported by Garfinlml in his aeslysia of the 7aerinn<br />
Canoer Sndety Stuly daa 124) . far eiFa.ure to epouse seaking of<br />
20 or :rore ctgattres.Iday he fmad an o00s ratio of 1 .10 . Sisilarly<br />
his results aeje aot uqnifiwM .<br />
5V£GZS909Z<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
-1uo-<br />
Oor results regarding tt~ .uvariable emuct be aommted for by<br />
the fi,alusiae of faoer senkarn sina aay effect due to this<br />
eirametnr.e wuid aC_ in th opgasite .tire+ . . . ., . that is, would<br />
inflate the risk attriLutabla to ama.uce. Nor asn it be esplained Dy<br />
the use of snsopte lnter.ie.e either, sime eo siep+ifiant<br />
diffetaKa.s ware faund Eet.e.n tle rtLetes fow the latter aM the<br />
eatiwtas for s.lf-resputls¢a . 'Ru eHsct aaold ntt haw he.n diluted<br />
by the irclusSon of mmles . siroe they sees to ahher a siadlar ruponw<br />
to that of w.n . Finally . m .qaal dirtrfla>`. .bon In ews aid ceattreta<br />
ragenSi,g om!ounlkg variablas ennt 6a raspayiDle far the<br />
fiediags . as *q)est.d by the airor dfnqe the estimstes mdecgo M>n<br />
those veriabla ara ineloded in the airlyefs .<br />
11a did aat find an effect depn0.¢ ae the d urar.tm of exposure<br />
to passiva smki:g a s sass¢ed by the an6es of ysan the sppse<br />
smalord rlSle .uri.0 ud livin9 mqetMr . i wo other studies Ird<br />
evaluated the effect attriEutable to this srbuie of aposors .<br />
Oalager at. al . (33) tepoctad ern slyelffaat ferrsw in risk d ue to<br />
s{uee simtdnq of 1-20 years (al - 1 .73, 9S1 Q.: .52-S .s2) . 21-30<br />
years Ipt - 1 .7l . 951 CW .60-5 .101, ud 930 yaaf ( 08 • 1 .24, 951<br />
0. : ./2-3 .531 . T1rae figures did nat slnr avidrr.y of a linrr trand .<br />
AkiLS . at . al . 132) reported od+ , rstioe of 2 .1 1991 C1s 1 .0 - 4 .31<br />
for tim .e a arrid to sndzrs of 1-19 ya.rs, of 1 .5 1909 as 0 .8 - 2 .71<br />
for those e,ptns0 during 20-39 years . ad an odds ratio of 1 .3 1901<br />
0.: 0 .7 - 2 .51 for thcse eaposed to 40 or aore years . Strtse em<br />
s(9nificaot effetn did ,nt shw evlds,ee of a Unat trend .<br />
6arfi+Gce :, at, al incorporated a different meenue of dtsetian of
erposore. ".1ey eatiaated rhe ar :ect associated with elqowre doe to<br />
hs6utl's ankSlq in the last 5 rd tee last 25 years . 'Cmse remoace<br />
of eapcwee . .um analysed fnt dilferent age gro,Rs . hisrnlo9ic types .<br />
type of respudu2, and socioecamic statw . Only om of 30<br />
eacfaetes oetalned alowd statistical signitirarae fat - 2 .38 for<br />
modera of the lower Mddle class esposed to spaee sndcilq in<br />
last 5 yaeral .<br />
itae svaloat .ioe of our third seawusaee of spas.e sselcing -<br />
toul :aa6er of rigesattea sadasd datieg sssried life . - dos not<br />
aoppnrt an aasorSatioe with lug wrces risk . fie estLete asscciated<br />
with a dif tarantial of aayowaa of 200 .000 dgaretres wes found to ta<br />
1 .018 (959 Ca o.8T/ - 1 .tet . ;'~!~+T+~~~as at . at . 127) used the<br />
a.e eessresnt to asars psair . .wkinq . 1Trir analyeis, laa.ever,<br />
rewlttd in sstJmtr that are relatively high (a thtee-totd lnaed+e<br />
in risk for eapxa¢e to 700 .000 - 400,000 ci9arettee) . and .+hidh also<br />
show evidenoe of a linear traM. Their finditqe persisted after<br />
owntrollirq for soee iapoetant wriabls . in our atody the Lxlusion<br />
of oonfomdLig variables did ont ptofooa any dreqea . that .aLLd<br />
reverse oia camcl•saiee of a em algeifinnt as.xlatlo+ .<br />
in the paraqraphs abvn .w have vallad attention to t.1e fact that<br />
factors ralatsd to the design of the stuuy, or ra t!r pceaeur of<br />
anfcrdinq variablu . mold eo3 explaln the diffetencee betueen oor<br />
rerllts and those ahorin4 a positiue associatioe with scvcse smking .<br />
Other ciranatanoa . hweaer . way Mve afir_rad oor results . Sonr of<br />
thse ate prese2e:1 as follon .<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
tra<br />
-1e2-<br />
t7ltim of the Lirst tra apadesioloqic studies an passive entlling<br />
raised the mr:zn that the resolts carried aK in tw foraLgn<br />
rnan:ries (i .e. Japan and itesos) adght iut apply to tlw U .S .<br />
pquiationl t]pasure to spaaa adtin9, it .u st .gqestad, wold mt<br />
be as good a pmay aeesote for overall aponce to sacloe in this<br />
cvuntrp as it .oold be in rlwr ann t:aditicnal sodeeia . In<br />
tMse sociatic ynw smokinq - it is beleived - nnt only<br />
oarelates Ye11 with overall eaponAta. but ateoally oomprisesa large<br />
ptnpxtioe of it . a rsre . t aady in the U.S . soqqests a different<br />
pieture for this m .ntry . FrisB.n at. al . 1921 have foud that<br />
determtntn7 an Lriividosb e.prors an the Csais of the spasa a.okinq<br />
habits aay lead to qroas errors . For Lrtann . they r.ported that 471<br />
of +amn and 3% of arn aarritl to aanlwrs npart.ad aem hoas of<br />
eapeeure at hons. Omversely . 40 .Sa of wmen ard a9 .n of sen sarried<br />
to nwraaokars reportad sae espesura to the avoke or otlrr penam .<br />
'Itie deqcee in Wch a aiwilar pmobla a.y alply to eur d .fa, ar the<br />
ysy in which (if pr..eeU it ary have affected oor easr aM eo,trols<br />
differeetly . ourpt be ascertained thto.qh the available infonatfon.<br />
'lfius, soch a po.sibility r.ains a potential wrte of aiar .<br />
Different llfe oaidittons le the U.S . ssy al .n wMs the use of<br />
sP2.r+e snWn9 a Ed peoay for diqaMUS to passive swakLg . tor<br />
instweCe, the a.erqe Japanase has is much wllar than th hnerion<br />
hone . 7b i(dlatas ot laue siae oad ty the U1td tations<br />
ill .nrretes this 03) : 1) The avetsge size, eeprasencad by the sesn<br />
ndmr of parsons par hoanalcld, is 3 .2 in Japan . Mereas in the U .S .<br />
is 2 .2 . an! 21 1x peeeercags of Inudnq untts vic, on, roos only ia
5s in .Tapae eM 1 .6% in this cantry . As watioed in arother seetian<br />
of vLLs rapert, soon siaa, tagethar with a cloaely nl .ted wriable<br />
- i .e . proxi.tty to the asdoer - qreatly influenoe the sponae<br />
dose actually rteeiaad by the {assira .mdmr.<br />
It might .ell be arqi .d that. sinoe sose reoelK nmerion stod/s<br />
hsve supported the finii.njs of Xiraysa and'thridwpculaos . objactioes<br />
suoh as tiuse ratsed ahoue Irae alraady heen discwnad . It .hould be<br />
eepfsi:ed, loeuer. - tfrt only the stuty Ey Urfinkel et. d . has<br />
slao siqnifimnt fiMilqs in the oarcexi of rasasreh vithoot sr jnr<br />
aaHndoloqiosl problas . nn additimsl study Illlayo tcrzea, at . a1)<br />
prsent.L qustionehle rwlts, pvtimlarly dua ta the nrll maiu<br />
of wbjettts stulied . flrcehrsQe the ot recent peper poblisled 1n<br />
thts cavdry ws unable to vcwr .ry statistically sigetficant<br />
a .sccf.tScn /0a1.q.r . at . at .) . . .<br />
20 effect due to spwr .mdcinq in our sady sobjecrs may be ao<br />
aaLL1 as to be ade6aeuble Wer the pssot mditions of stcdy .<br />
SLeh sffect, haiever, might M11 Wm~a detacreble if espeson ftae<br />
differant sourees uere to amouLte . 'lhe fact tht s fowd an affect<br />
d.e to asFas:re in the lousenold - which lnclodes the spousa's<br />
seakin7- atmqly soqgMte this {wsibility. Sudler'a fLdi .-us<br />
furt.Mr support it 1771 . Be found an lfxzes in risk with the<br />
increasinq nuber of hwWnld rembers do amked, lncludinq the<br />
spouse . Lwition, toqnilrr with theae resolts . rculd ses t] suqqeat<br />
tlrt chs enst sWropiua ray to evaluate the effect of pesaive sdneg<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
-1a4-<br />
wold be tLmiqh L'se o .se of a c-ualative itder of esponure . Altfouqh<br />
in thsy this is driraels . the si4soas of ©llectSng the<br />
intomtire smy p.v.crlbe it . Fecple's pe:eep[ton of Hr amam that<br />
goes an aremd t3r sy sary frm pr cirvst .nee to anether .<br />
Nwreaa paople wy 6e able to prtwide mre or less dstailtl ant<br />
eocraate infors.tian oe the smoldnr, ef the spouae nr otlrr amtaa of<br />
the fsily, they eiqht not be s pa.els. Nun it oo.r to the sarhinq<br />
of others or to the amkinq that oaxra in pubac pfaoe .. c~hy~ynq<br />
such infornation 1n a single iids osold rwlt in the aixi'g of<br />
"goN" quality lhformtion with sca . "hed• quality tnfoneeian, thus<br />
d'n~ tfr prut.dtlitis of finding qod eatls .mn of the<br />
effect .<br />
Ia+tly, an esplanstion for or negative fiMiiqs stiy oe<br />
attributable to the fact tlat .ukinq by the spouse is an asizn¢e<br />
that is inucmu oed late in life and .ay not be prelolqed drs)h to<br />
pram = an effaR in and of itself . 9o b eqowrte, hdbwr, muld<br />
l+ac®a inpoetnR in t!n praae~c. of a prevlous .aposor, hisrory (i .e .<br />
P.cenril mucking ) a' . as e w lalnrl a6d w , in conjisction with tqnin¢e<br />
fro other sarces .<br />
ua foud an inaease m risk fo< tonq cancer for tlese .3pesad to<br />
the serJoe of others at hom . 11e odds ratio abndattl with ISO<br />
peneNyears of c4oeure Ms sifnwted to be 1 .86 (ril dl 1 .22 -<br />
2 .6I/ . only a few previeus sncis have included a arsurvaurm of<br />
expowre at lwnu as a .isk factor to be Mluated. in socA snriia.<br />
ho.erar . CSS ftanmrenrr_ of eq>oa¢e has S..n ndimntvy, u>u.lly
-ts-<br />
.upreseed as a diooCoey (Ye+ .^•n wGIC1111rel . we believe our<br />
eesau==sant to be aore wWlete given that it cenpr.aas a prury for<br />
the Lntenaity of the a~osuta (n .eher of sokeia in the Aoud:old) . as<br />
wll u for its d :uatSon (auesr of yaars of colrbi*nt .ion .rith<br />
>edssrs) . It on also be raqardsd as a auptaMiuive aeeaue . at~te<br />
it irclodes all Lo,saAold sbaw for the subjacts' ruidmroe histor! :<br />
(tM latter ekpudLq for the rost pstt of slnir tl+lt 10091 . '!ha<br />
wllertion of suT sasniva infometion, twea.r, w oot .attwt its<br />
proClm . ws evida :od by the owxxaoca of sae nissing vadrs . '.e<br />
have eq+lained the rkys in whid : ra aR'COd"Id suc+ lc+bles Ity<br />
lopotation of aissin9 saluu wder tw diffarant aswptio:u) aod feet<br />
mnftdmt ttet our e.sults have not been 0•"6t-^'"11y affected by it . .<br />
'IIw follw" are tle rwlts ftv oUrr studies assesrrg the<br />
role af e:@wura to pssive s.0kieg at hoas .<br />
Grfinkel ai . ai (30) alauifitl the o¢owre to s:dw at Aone<br />
ataOtQlrg to Aw ts'Hlt 1Y the asponlte . 1Nt tlwse axpnad at Ilose in<br />
the lut five yeats (yp[ne apas ; asl an odds ratio w fovd for<br />
lmg tancer of 1 .22 495% Qa 0 .92 - 1 .621 . M .vaA 1~ astJarte was<br />
rapertad for expoeun In the lut 25 yesn ((Xt - t .15 . 9S1 Ct. t 0 .69-<br />
1 .19) . M1tree results vcf ::ot ststifCitally siqnificar- . as a1w.s: by<br />
the etetiMn.a iatarvals . A stre sef.ierd aeaacene:t of e"ora et<br />
io,r .ae also assesad by Garfirvmt . but it rs limited to spnne<br />
®nki:q . A sig:ufiomt tlnear assooiation ss :omd fw e:pcnure m<br />
the speLLSe smokinq at hw (no aaaxiation r .e foaN for the sneiti-q<br />
that occvre ourside the Aeae) . 8atdler at . al . (37 / rapertad ar.<br />
eleVated risk for tkaM a1QaneE at kaef . 'f!e oddf rYtioe alsotla_ed<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
-le6•<br />
rith 1 . 2 . aM 3 or aQe tdcinq hwsd :old ar:bers y .n 1 .3 . 2 .3 and<br />
] .a . tspatt.iveiy. nrn tlw :qh oalf the last fiq.ae .as in itself<br />
stati. .i.+tly, sigJtiont . the tlren figuree toghether follw a<br />
statiktieally si9ntfieant li:rer ttend . Rahet rd MyMer (34 ) foond<br />
no aseociation 6en+en eMOMte at Aune (yr/ro e .pasural and risk for<br />
luq aaoer . IIrtr estieattl, ho~. are based on a study that<br />
included only 25 laq cower prieras .<br />
In additica to the oweralI effeet doe to hoiudold esFVaae fnad<br />
in o:o: data . there ts one other finding that das .c ves tpecial<br />
consu.ksetioa . 79 :e affeet ' of psufw woklnq in the hvauhold %s<br />
fourf to be siyetfionUy larser for apid.vuL!/s a il esll histologic<br />
type t1 .n for adsnoett ina m/eeler odls histologic type luad}rer)<br />
odda twtfos af 2 .07 aad 1 .42, tdpactiv.ly) . Cmtiollinq for<br />
tanfoirdLg variables rwltad In utlrtr , that altLough tnt<br />
siqdfioant , yra nwntLalaes oeirietra witl : the aho+a findings<br />
(adjust.d (M - 2 .12 , aM 1 .li . t.spu.tiwly) . As ekplaimd•in the<br />
paragraphs abnu. , only a fer studies hsvu classified their caeu in<br />
regstd to :Wto)oqie dlagnesis . pd ewn tewar have SneloOad a 1arq.<br />
aaoqb nurtar of ' wes of eatA histologic type as to 6e able to<br />
vasdna speeifit assadations . ttr rotSon that pessi+n rakdrg sry<br />
be more strongly asocaa-nd riN epldunold tt .ora , therefor.. mas<br />
∎.inly fran studias on ~n e effeces of direct amkieg . Alriouqh soaw<br />
of these stuCies t :ave Cete!riend that all lutoloqit types are ralatad<br />
to snokinq (aee CU xar 1 : •Sn>kSeq rN 8istalaqie iypa of 4keq<br />
:anoer") , ecst of t.'ae s!•on to a.pw that the strongest relatlanship<br />
is obsarm d 'Q epa!er,:o.d ur) mail tell tunar l . Te suqqesti.n that -
auch fiMUys hold as Yall for pssuve madtLq pxovinn np0ort to J*<br />
hypotn ..is that ens.-ito.e,t,l make acn in a sle,ilar .ay to<br />
w,.me.o smaka and tk.t K---s-- that tk only di :ferences between<br />
the tw types of etpesores are quantitative . 7h0 one otler study that<br />
fomd a statistically signifimrc hiyhe risk for ipidrrvn!d type .a .<br />
that of Cacfinrel's et. a1 . 130) . '(fry ra0ortad an odds rstio of 5 .0<br />
1951 Qu 1 .43 - 20 .101 assoriated with th6 kWa'd's srukitg at hose .<br />
Juietler study reported simiSar resoltv alt]au9h non significsnt .<br />
O.la9.r at . al .(33) reForteS an adiustsd odds ratio of 2 .66 (95% C :<br />
0.91-9 .101 for .pidereoid/snWl wll ateitaa•s . and an eidb ratio of<br />
1 .02 (95% C : .33-3 .161 for adcuwrrinos .<br />
'fis lapcrtana of psasive seoking in rlr teusdmld ant be put<br />
l= perspective with r.gad to the aoa.rt of 4XIasore nemo .ery to<br />
olsyrvs an effect of the sspnitude dnQihtl. We have pces.nted the<br />
utl.rtes of effects aaeclY.erJ with an exposure of 150 pmaJyeers .<br />
This is cqnivalant to Nvinq lived over a period of 30 years with fiw<br />
sokers, or with appearlestaly 4 ss7/ors for 37 years . it should 6e<br />
eaphasila0 that sodl 1M1 of exposure !s rather high and my be<br />
uroanon in the general p:qutatlon . In our study qtaQ. for iesrance .<br />
only 7.54 of the wsn and 4 .3% of the otRmLt attafntd that or<br />
hiqher levels of a¢oaira. lnlssd, la+er levels of exposure are . .ch<br />
sort caman . For example, Z56 of the oeses sid 20 .5i of the tvntrols<br />
eeporttl eAoau
-149-<br />
ef the family eey be closely o0trelatd with the dc7e received by the<br />
pessi•x m0is, the cort alati0n betwe.n Oo- .arYSrs' swking and the<br />
d0ee se0eive6 by the passive sakar msy not be as close .<br />
1b other stvdy Befon Oars h.d LnOludtl the aseeymmt of<br />
a,posute to pas.siw amking in social eitusvas>s . We lak,<br />
tlssef0ae . any point of catereca by .hith to campare a0r mumpecterwlts<br />
. We f0oad a deet+sse Ln risk fce U.e9 Orka with i0onesed<br />
eiQ~onue to an iMnc astad to rK1e0t sodal pmLw tMng .lOn ~<br />
0 .639 . 95% C1. : O .S20 - 0 .765i . OLven all the follovieq - 11 the<br />
Prevaaa reporu that have sham an asscdatf0n hewa0 espow¢e to<br />
pesaLea >mhiiq ard Wtq enar . 21 aor ao e+sults that sopmrt soeh<br />
telattOnslnp tat l.est for oee of the opOwaa v.riablesl . 31 the<br />
aGdiss that have ufablishtl the assoeiatl0e heerarn actiw addnq<br />
aM the diaseue . .nd 6) the latOtstay dsta that hu cumfissed the<br />
or-iroq/r1ic propettLN ef teCrm ssOks - tIr pOSSlbtlity of a<br />
Ourtradir.acy effect of pessive aoklnq a6 lug cano .r risks ssrns<br />
oMOOMid .<br />
In ssRhi+g for ae sxplanstim of this rwlt . ye eat easider<br />
tw possihilittesa Il that the association fasd tefletts a trw<br />
reiatlor-ship ,<br />
sid 21 the<br />
the teaulu aoa p[oMet of data artifacts . A<br />
third pasiDili'y . t/!@ tola Of c.hmee . hu larqely heen dismunted<br />
thmi9h the appliation of tests for Miich the statistiCal<br />
siq0lficsn0e has been set at O :OS Ii ... CesultU su0h u the mn<br />
owtvad mey have Oce.aed as a cauequeroe of tlrrce mly .In S oot of<br />
l00 'ttials•1 .<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
-ISU-<br />
If we assne first that the relattauYifp fowd betkeen social<br />
eaEaeore t0 passive smkirq las m5axUrad1 nd lusq mxar is trae- we<br />
well miqht ronder .ent oo01d have Oso.ed tng cencer patlgnta to have<br />
heen e,Waed to less soclal Passive aekitsl than .ere the •heslthy<br />
emmols. My response alow tlnse litr rould be eerely spewlative :<br />
hut the toilov4nq is ar that hes o.=arnd to Os . aqpae thst the<br />
msn have ic:leed developed the disease as aconseTaence Of espOSUxa<br />
to p .sive aaekinq . AOmtdln9 to nuc rasultso the 'ca0bal' espon¢e<br />
.wld be ttr. One drrivad f_=m ssddnel Ln the hosdnld : that Ls, fmm<br />
the cnly esmaura for rhieh ww foud signifitstnt results . It oould<br />
ttrn be a.-gt~ that the aponae Mueh a0cata in the hae eamot be<br />
avoided lor . wmt be easily awldsdl , whn+as amposura in soeial<br />
t4resstanoes is sontlsinq w .r Mioh the Ldlv16a1 has a certain<br />
d.qrss of ontrol . If tho .. W o ar s to develop img canm deuelop<br />
early respiratory syaprau las is avi9uttl by the fact that lunq<br />
oncer is otter. ptw0eede6 by a poor easpiaMey fvKtiOn (6711 . they<br />
mey dnoea tn avoid am@onae to s®kR in soelal dmsnsunoes . lut<br />
fLM it harder to do so at Ma. ihOs . empOaaY in ttis iswtlold<br />
w0uld aaneinue to petmit the dissa.e-gariati0n pmcass to be<br />
aqflettl, rhile at the sasis t!s epos" fras other so0mes .oold be<br />
dSsinWhed. SimLiarly . it Oculd be psOpead thet . in additio0 to<br />
pessive ssoldn9 in the haralnld . tMn is an aa yet widsntifid risk<br />
factoc raqanai5le far a OOnaidsrable peocotti0n of the<br />
ases.<br />
inCessLg esposOre to n ich a risk factor a+orl the c .ass . heweVes .<br />
~,'d alse MVe to be asaodaW with a dsaessinq axp a0n to seclal<br />
passtw siNCLg . In this Ysy the tswrsa association OOsaN .d hetwe .n<br />
social fwssxe aoktnq aM lunq caneer wuld be nst, tslt by nu menu
vmld be 00113241 .<br />
/l acroid possihility rs !rw to:ridarad is that aor results<br />
te+podiog socal urpaw" an artifaenul . Nut is mst liloely<br />
rar.pndble tor this is the ose Of se eS..~~ ~~~i ~~i{e Lr3mt of atpowuas .ct<br />
pcevicusly vslidated rhtoqh petpstAodoleqic atudiar . Sone<br />
fwtats %ftich ay eew atfe=ted w yuaity of tae iofo®etioe<br />
collaud tAroqh w ch modwiies as follcr. [int of .11 . the<br />
prsiod of tias conar.d by t!r qunrlaarlR ltems is v .ry lealtlry .<br />
LlititLq good infooetiod oq d .y-m-tYy ew.ets in the Pbt seqoins a<br />
omsldsrahls effort of rear.llasion. /erN^lArly<br />
for the first yeats<br />
of life . a o~stdacable raaoilsetiae of th qraR's or ttr faaily's<br />
eoCial life, M1i~% LLf th Oill v9l{eie of tl( os tre to flWirono RKJl<br />
Man fa , is rill/ired.<br />
S.mrdly. rh intanstion o lt rs oollenad d!d rtet wks any<br />
attapt to r..nse intrialty Of 409awas. aor did it ssublirt the<br />
relative laportatnl Of eapowas dorLq ar activity as eplr3sed to<br />
anodar . fiere is a tr1 qusat.ioo . fur itutrns. if visitinq fdends<br />
ar relativo Mn secke mAeys tM s+ME dr,e .e Of .XponeMP as wold be<br />
inasred by qoinq to Eers aM nsuunnt. . 7>tus, exyomta for all<br />
activities .as riigeud equally .<br />
ihi.-dly , the .pecifS.c sodrl acLtvitias apecifitl to the<br />
imarvit.ee in oeder to elicit a nspe»e - tlrt is . t.hane<br />
repras..RStlve activities feon m be cvdsive to e)q osur. - yera<br />
\l.ty lieC`Ad (fRe 1iQFiC'IZif n. :Yge 1711 . fbr INCV f ;alAy sub ]eCCS L'10<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
,xpcavre might originate fron vety differant sarts of smial<br />
cim.xe'uanoes thnr: tLose explidtly qoesciond . The faaure<br />
spe=fically to rentim tlnse activities wy cmxivebly have<br />
pivduoea so"e ""'' ~ a ,<br />
ktacth ,<br />
the ose of dic differatt onits of tim to eeaaore<br />
frequac7l of eapow.ro .ey alsc have oanitued the tespadm .t.s . lbe<br />
less fregoeit aqioartes iud to ee reportsd lceadi19 to the nmber Of<br />
tises a uurch ttn es{awrs oct=a d. Mrrsss the eost ftequent<br />
eq~res had to be r~ ted on a par/wk 6uL .<br />
Finally oxVrenensim of tIM infotwtlan being nqeestad sy have<br />
• Ifeef jpLj-ed by the ceples IIetICe of the qlMtiols. FJCd ilquiry<br />
deffitlGd reslMN/ UlliGlf s16tlltaeeClsly sy/1C11etiAd illfo[/wt1C1` OIf<br />
three diffeceot .spects of npoeun /typs of saeial actlvity, age Of<br />
aqowre, rd frechercy of empes :rel . 8uch qoutlms . Plaond ahmst<br />
at the erd of a on hoau iMatvi.r . ry havu Eew+ aroil+red Witlnut the<br />
=,muentretion ntasssry to ptwlde altoqaNMr adequate taepansn .<br />
W Osw• not emticn in the above list the ur of turragete<br />
raq :(dr2s as a po.siDle sourc+ af data artifacts .'Cn re.son is Wt<br />
r do net have any evidenar to support that tlr estiartas ^^••'- e ' for<br />
self-respudents ars .ey diffarent fros eM . of sorcaqste aespwde
lsperfact:au of the . :a:a colletc:cn taola alone, haaver, ney<br />
noe be aufficient to uPlain o,:r rasults . It is the .ny in Nuch ncn<br />
laper?ections affectwd the respmse of zavs via-a-vis tx res{mse of<br />
cartxola tna: any ptc.ride addil~1 m"xieratanditq . .gr : .i . .e can<br />
anly spern:ac- on this satter . Our --es'a17s sUqqot thnt the ceaes<br />
owy )~ wrlerepcrted their aioorue to eaeLl pWiva sadcinq- 9uh<br />
a p[ralea is otten sentiae .d in relac-an to r.Hies in .Lich the<br />
surycsed e4.wure fs ao=ially us.4sitatlew as is tho aae vitti drug<br />
or alaohol use . in the present i .'v-snte, Nuewr, there is no anh<br />
stiamti :aticn attaiwl to espoeote . Lt is, attet all, the wdcM of<br />
orliers . aM mt the patient'a wn risk fnetor that is being<br />
lsplieatd . xeuer,hless, patielta for vhateiar reason my have felt<br />
the need to m"vnimize tMi . Cyoaore to anything that potanttally they<br />
mi5ht have been able to avold . IfNorepo[tinq of eVisu:e by cantmis<br />
asy aiso . in tlroory . have piod~x.ed the results aheerved . In practice,<br />
tw.ever, there is no cviollicg raason to baleiva that cantrols '.oold<br />
benefit frvs such bdsrviour . As a maeqoenre .e Aeve disownted<br />
o.ereportiry as a poesiDility) .<br />
'CrcowlrrK this doneent re have presented a sumery of Cie<br />
inforaetion cvr-mtty available cn the relationship bet+een lur,<br />
crKer ud passive simking . Li ,he !sst part re !uva revi-wd tx<br />
nepr epidenieloCic stvoies en the wo7er.t, as Mell ee aoae rele1nnt<br />
laeoratcry data . Sne a .jcr pos•1on of this dac~ane+t, haaver. nts<br />
yeen devoted to t1e dee. ..-ptfon of tne setbdology and the results o!<br />
this . laryest epidemioleqle ruM' so :ar _^.cdr,rd to rr.,ins the<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
afotenentrmd assoclatian . Both the streqW aid waak :nasaas of . the<br />
study heve oeen ftdivred= Wt Mwq tlwe are pur into a balance, .e<br />
helelw to Laua gathsrd ar ot the 6 .K dau aeta to ju* the<br />
estmse of the T¢pY.ad ralatiauhip.<br />
Ye .err aeble to mnfism an ~.-'~ atio^ with the aat cvmnnly<br />
used ea .wao of apoaure fspouse wdtin7) . bnt e+ did find an affect<br />
doe to eqoeare to pasive swcict-4 in the Iwsetnad . 'tlnaa retolts.<br />
altFnvgh only in paetJal agce+smnt wdth tlw of otl .r sddias, are<br />
vamsiatent rith the .xistaa of a s•all to sedersta etfect af puaive<br />
eeokLng on lun7 neoer risks . 14 did eet tJd an effact ive to<br />
eq3on" to a ssaivs aaycLq in the wtlPlaa .. We fasd. lo.ver . a<br />
dsaeuad risk in lunq unoer with :n'^°e' nq aa@oeure to passive<br />
aackinq in social drnnreanas . FeesiEle reesma for suCt findLps<br />
Mve been dfaaused aeoue .<br />
Out fLslLgs au7yast tAat the prwims atudiae .ry have<br />
orecestLsted the elfect attributable to passive asoMrq. 9Lvh a<br />
ponat6i11ty tias 6 an pcqsie7 by tMr Mc oatand that a typiol<br />
aysaora to passive tddny is tely eqoivalurc to arekLq actively<br />
les than oea cigarette per day IMieA in itself amveys risks that<br />
are lowr than the tw-fold incswe peo{rned for pwfve ssekLq) .<br />
Itrtlydaloqlc prable e that say !we ld to sor h over.eeL.tion of the<br />
effect have tsnn poifrcwl oot in Crpoar 1, as aell as in this thsptee .<br />
As Is .aIl lmowa to epidmuoloqiscs, the rwlts of ane ac+Wy --<br />
or even a few stodies-- are seldm suffinarc to ans .er all questlou
-1i5-<br />
te :atd_-g tlfe -vla~toM1SVg b9t!en a pnn. ae t3k factor e.ri a<br />
disease . We belelw•e tne present sRct/ :vs anCibuted to a 5etter<br />
mderscrnding of t.he lun9 caneer risk i+rvoltai !n Ue ea?oeore to<br />
passive smoWn9 . Neuertheless . we think we are sti11 far fran<br />
Icnrirg al1 tte details neoeasart to eetaolish a final judg,e• :t .<br />
tut=e studies vil ; be necewry- to tvte tMt steP .<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
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21 Elnrieon, M .J . . A prelialKry tcmrt on ciqarette esdclm arrl<br />
the 'sutlence of prwmturity . Me:_ean .~ of f_bnirtac3 and<br />
Gy ::taniogy ;1957 :73 . 807 .<br />
31 to.e, C. A . . LSfactv of oaBMr's saokieq habits ee bi-rh<br />
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1981 ; 283 : 1363. 0<br />
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:mmuuaation. 7M t~, tYhvary 9 . 1985, 312-314 .<br />
30 Svdle¢, D .P ., El+reon, R .B ., Mil®[ . A .J., Bro.dec, J .p .<br />
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5, 487-492 .<br />
37) Smdlet, D .P., Evereon, R .e. . Wiloa, A .J ., Passive yioking<br />
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bbl 121, eb . 1, 1985 . 37-48 .<br />
381 U .S . Departmne of Health ud eu.n SarvLOef: •D :e health<br />
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421 BLrL. . W .C. Aed Pi.-at . M.V. Conoeftretlmr of nicotine ard<br />
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292, 844-845, 1975 .<br />
431 lA .pd C ., itaMdns, L .B ., Aetny, P. 87qnaot.a of Matve<br />
Bedrere to ootecco secke oontntvelrca . L:t ArJ: Ocup tSlivn<br />
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44) Ttiebiq r,., 2obar, M .A. Ldo:; ai! pollution Ce = olre<br />
mutitumts . A wcvey . P-eeent.ve Medlci.x . L3 : 570-581, (198a) .<br />
http://legacy.library.ucsf.edu/tid/dsk94c00/pdf<br />
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45) Jarvis . n .J . . Setua thitcyenate in oesaive saoiiaq . :he<br />
Lanoet . Jar .av-y 19, 1985. p 169 (letter) .<br />
461 fliitonal . Brewtlssng other pacple"e suloe . Britfsh MeAml<br />
Journal . No 6135, p 453, Aug 12, 1985 .<br />
47) neeting repoet . fYqht Interna- tlonel IIM[itq an M-•titzaeo<br />
oaFnmd: . Jciare .oe . Sioloqia.l effects and relevenR to haen<br />
enxrr. Cancer Pesoarrn. 44 . 1301-1304 . Match, 1994 .<br />
487 U.S . Oemrtma .t of Beelt.h and Munen SerrriQe . Public Bealth<br />
Swloe . The heelth oasa~ ;e;tae of ®ddllq . A repx2 of the<br />
8 ; .-gem f+meral . 1982 . DBBS Whlioatim No (PIL4) 82-50179 .<br />
49) Bnsnmem+ R .D ., eoffaam . 0. aeeial BtWfee on taheeco<br />
salke . LII. Analyeia of wlatile nztztwamulea in tomam emke and<br />
pclluted indoor annmeenu . Int Waler . C.A . . (;
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551 Ardernm . W . e . . 3[iGlr.' . C . . dM l.vc-_tt . J . .nwtt:taticn of<br />
sndcu,9 in pe::e:Rs v:tn s.:oci:q relared c'4ae . Q:eet.<br />
WI 76 !31 . 415, 1976 . (Aosc.-xc21 .<br />
561 Mets :luua . S ., 4aauastA . T., NotikasU . K ., et . al . CfecrS<br />
of errvims.rrtal rahseco snxe or ,:ruary octinu :e emxetiorn ia<br />
mrv :oken . 6videnoe for Fase :ve ssedn9 . N?w rMlard Ja:xnal of<br />
Me,iicine, Sept 27, 1984 . 828-832 .<br />
S7) 6wld . N .J . . Bo [ehea. J . . Friley . A., et . al . Urinery cotinine<br />
as meraz of txest~niny otlri people's toh.cm mcko . 4fie %enoet .<br />
Ja:uary 28, 1984 . 230-231 .<br />
S81 Meld . N . . Kitc.hie . C . Valtdatim of stodi" of lung canaer in<br />
aatyxdrets serried to saekess . 7he farcec . !ny 12 . 1984 . 1067 .<br />
591 Shiyeru . N. . T®dneto . T . . Kitarto. N ., et . ai . Plfecv of<br />
envirvoencal toEa® 6no1x m urinary eetinine euretim in noM<br />
s>okacs . Nev pg1aM Jamml of etedi 'ene . Sept 27 . 1984 . 828-832 .<br />
60) Jarvis M. . 'MSrall-Padce . B. . Peynaberd, c. . tlsey . C. .<br />
Salleojee . Y. B :ec':emiwl eerkers of soole ahearptien and selfrepnrted<br />
expos,ue to csasive saYNnq. Joiaml of Wdeniolo79 aM<br />
dmmcitv Health . 1961, 18 : 335-339 .<br />
611 Mtllaz, P.C. . M- Cimkar . K .T., leaeder. M .K ., Mglaoe, J .D .,<br />
Booe . R .C. Dq.osition of sidesrawe smke in LM !s®n<br />
apiratory tract . Amec Rev N Dis . 125, 406-408 . 1382 .<br />
62) Killer. P.C ., et. al . Deposition of sidestresw cigarette<br />
smice in the hm6n respiratny tract . Pceventive Medicine . 13 :<br />
602-607, 19di .<br />
63) Mitd.ell . R .I . Cart.col!ed aea*usent of eaolar particles<br />
reter2wa ia the teapiratory tsact . .r Ja Nev RsSp DLs . 85 . 526-<br />
$33 (196.) .<br />
64) Bepr.w . J .L. . W-rey . B.N . Iad7or air pollution' toLecoo<br />
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65)tea.c . C . Drnt :tative aslncce of paastve aokieq aM lon9<br />
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661 Lynd. . N .T ., et . al . Genetic aM simkir9 a:aaciats oncers .<br />
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68) Ksuftaenn . P ., Tesster, J-P . . urinl . P . Adult pelsive sCOking<br />
in the hone emaxvve,x : A risk factor for c9rvic a:r!lw<br />
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269-280 . 1983 .<br />
69) NLLte . J .R. . Froeb, B .P . Sra11-aL~ . .ys dysfuec[ion in nmsnabr.rs<br />
chronic.lly esR:eed to tn0aem sol : . ttv t5gland Jau-el<br />
of Maticine . 302 (131 : 720-72J, Msrd: ]7. 1900 .<br />
701 Chef Yue, fa Men-ltise . 'me effects af Paseive aaokirq en<br />
rhildren's pulamary fsmction in Slwrlai . leenon Jamal of<br />
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71) My :drr L.L., Ocodloen . M.T . 9nokSnq and Im:g tincrr : So.e<br />
ut¢wlved iasw . lbademoloeic Ne.ners . Wl 5 . 177-207 . 1983 .<br />
72) Fbllaed . 8 .8 . . Pnrlamki . &J., Bocker, L. 'D :e effects of<br />
eiqarette saoke aa the respiratnry systes of the raMit. A final<br />
re{prt . Ca:rri . l6(5) :612-615, Mty 1963 .<br />
731 Saffietti . U . E+~erlaenul respiratory tnct urcinagemia .<br />
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741 Mrnder . C .L., fnfhsun . D. 1eAaceo ad oo6ecco sneke . Sndtes in<br />
experinmtal rarcinme:esis . New York AcadeAic Press, 1976,<br />
730 lp .<br />
751 shuhik . P . 'Ne use of the syrfar. 9olden he:wter in daaLLc<br />
t=Cty testing . In, Nmiuqoer, F 1@Sitor) . ess in<br />
f5merin.rcel'llnor P.esear.Yh PeWlory of the syrian hanstar .<br />
Vol 16, Bseel, 5 . Kac~ .<br />
761 4tiiffith. N .B . . ard IYncod: . R . BLa!taoaous saiearzesesiddtreae<br />
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77) Orns . L . . Var, Dooren . B .L. . 9nsak . A .I . . Neleor : . N ., SCmitt<br />
P .L . t+e cuciu~city for aane akin ard the arrnetic<br />
hyd~acroon cmtent of eigarettr9roke osdettsates . .7o,mx1 of<br />
C.Y Nariaxl Cancer laotilute . 21(31 ; 557-:61 . Sept, 1958 .<br />
78) Creenbeeq . R .S., et . .1 . . Inddmce of l:ag uurrr by oell<br />
t9Re: APaWlatim-Caand stody in ta•w 8aapehire ana Vemqnt .<br />
Joutnal of th Na:ional Canoer In!r-itvre . W1 71, .b 3 . Nerch .<br />
1984 .<br />
79) Doll . R ., at . al ., The siqnificsnae of cell type in re.arlam<br />
to the aetiolegy of lleg cuvr . Sr . J . Cancer ., 1957 ; 11 :u-48 .<br />
80) Rny6riq, L. . Risteloqlal luy oraar cypes . A<br />
aupwlogical a :d binlo9iml oarela:am . Aera PsL+el .<br />
Niacbiol . 6 :d. 5pp1 . 157 : 1-92. 1962.<br />
81) Neias . N.A. . Rosa :siaig . N. . tleiw, N . A. . Risk of luy<br />
car:cer acm :di:y to hi+toleqie type a :d cigarette doeaqe .<br />
Jomsl of tne laerian Nedicsl Aaeociation . 1972, Vo1<br />
2a : '99 70T-<br />
.<br />
821 Yesner. R. . .7elfewl, N . 11. . ald Pelnseain, A. R . . A<br />
reappraisal of hiscaced»ltary of tvs3 wber aM wmlatioc of<br />
cell type with anteoedcR ciqaret9e ssub . JYrr . R,!V . Res . Di+ .<br />
Wl 107 : 790-797, 1973 .<br />
831 AuerSac.h, 0 ., Gsrfinkal . L. . Parks, V. R ., Niatoloqie type<br />
at Imq onrer in nlation to aericinq habits, year of diegnoais<br />
ud sites of ne'astam es . CTest . 1975e 67 : 382 - 387 .<br />
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