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Lung Cancer in Gt;E)FFHf:Y 0. KAt3AT, PcrO, AND FRN`3? I 'd1lYNl?1=12, 1%41') Among 2668 patirnts tvith neit•1y diuRn<rsed lung cancer interviewed bt•otc•t•n 1971 and 1980, 134 cases occurred in "ralidated° nonsmokers. okers. The proportion of nonsmokers ;tnton_ }; all cases was 1.9% (37 (if 1919) for men and 13.0~'0 (97 of 749) for women, giving a sex ratio of 1:2.6. lireybcrg "I'ypc lt (mainly adent>carcinoma) +•rts moree common among nonsmokinR cases, especiall- v tsonrcn, than anion{; all Iunl! cttncer eascs. Comparison of cr+sex %.ith tquyl numbers of al;e-, sex-, rrce-, ,trI d Iruslrital-ma(c•Itcd nttn%mul:in?; c•untrol% .httNCd nr, diffcrcnccs by religion, prs>pcar(iort of foreiQn-borrt, rn:.irh:ll .(:ttus, residrnce (trrhan/ rural), alcohol cun.ump(iun or (?uetelet's index. Dtale cases tended (o hani• Irighrr prupartimns ttf profr.- sionala and to bc more cducrtted than controls. No differences in_ ocrupa(ion or uccuputiem:tl cxpo.ure Ncre seen in men. Among .vornen, cases ..rre more likely than conlrolx to have worked in H tcxtile- relattd job (relative risk = 3.10, 959(% confidencc interval 1.11-8.64), Irul tirt• tiit;nificance of this finding i% nn( cletir. t'rcliminitry clatrt on exposure to passive inhalation of tobacco smukv, rrvltilotlrlr for rt tinbwt (Iran of cnses wncf control., xhoHt•tl nn cfiftcrenees rxcep( for mttrr frt'ctut•nt ral)o•ulc nnwnt, male t'nm. controts to sidcstre>aut tobacco smoke at work. '1 he nccd for more runrlrlolt• infor m:t(iun on_ e.spuaut• 1ir secondhand tobacco smoke is discussed. C'arrcer 51:121a-1221, 1984. A t l 1IlcltUrll ((INO c ANCI R risk ts slltln},1y aSSCkt:Ilt•t1 with ctgarettt! Snloking, lung canccr does infre- yucntly occur in nonsmokers.' 2 Several everal features distin- guish lung cancer in nonsmokers from that occurring in smokers. Firxt, most cases of lung cancer in nonsmokers are found in w•orncn '' Scc'cartd, thc distribution of his- tologic types of lung canccr difli•rs between smokers and nonsmokers.. In smokcrs thr: epidermoid type predomi- natt•s, c~Itc ri t, in nttntittlirkt r. :ulrncrt':ut inunra is ntctrr common, cspt•ci:tlly in wonwn.: ` This article presents data from a casc-control study of nonsmoking patients with histologically confirmed cii- agnoscs of primary IunF cancer with rctEpt...t to histology, dcmop•i:iphic f:tciors, ic.itlt-nce. E)uctclct's index, alcoIrcrl consuniption, prcvious discatic11a, ct'ccllPatton and occu- pational ckhctstlrc.s, and, to a limited extent, cxrosure to the tobacco smoke of others. Due to the small numher r-..,.., .t.. ,,:. VV9Cz2K3Z02

,,,.,,bm tJl lurtb canccr ()Inl'r5 Uc-t\vGCn srn[Jl:crt and nonsmokers. In smokers the epidermoi ype predomi- E rrtm Ihc I)ilitlon of I?ftiJcmittlop. Mahttnc) Insli(,itc for Ilcal(h rllalnlcllanic, '\Inr_ /l:an Ilcalthl'tlun(I,Uuln. ]?(1 I-.:r.%l •1 hJ tlcccl, F~cls York. XcN 1_•orl Su(slxsrtcJ bt 1'ational ('anccr fnilitutc l:onlr.tcl N01 •t'P-UShr4 and grant CA•?_'6I'7. AdJrrs_s for rcprints Crcoffny C kabat, PhD. f>i.ision of [pidc rniology. \(aht)ncy Inslitutc for kicalth RlaintcnancE. American Hcallh Fuundation, iM t'ast •tZrd Strcct, Ncls York. NY IoO17. `nce authol~ Ihanlk the follcswing cuolxrating institutiuns anci rndi- aiJuals for Ihr i%.Iluahlt cunlrihutittns Mcunorial Iiu%lrilal, t)r I)atid Swhlltlcn/cllt, \1a dr.tltan \'l-liran•s Illtslut:tl, Dr Nlxtltn Sltnlr, l.ctnl: I.I.IrtJ•lclli\It Ii-II, 1,Ic N Iq,1Wa1 ( cnlcr, ( )- AnI, lu S.n.lt% l y, lMilcr%ltN ufAl,thama Illl.{l lal, I)r \1'lllr:lm tlluft-crh. Itlrntingh;tln \'clcr.ln's I lu.- nltal t)r. Ilcrlnal• I" I chman. I_utola I_inlvFnit. li\,sltllal (C h1l.lt;lr). Dr. Waltcr 4, \\,,(xi, Iltnrs \'clcln;;•s lioshital (Chi:;ts.r). Dr John Sharp. Ht\.hilal of Ihc t1rncrsils of 1'rr,)%t h ania, th hrlnn M. I cvin; Jctli•rwn \tcd1i.11 (',tllvl;c •/nd 'lltrrnt:r~ Icfiil\on llnitclsily Iluspilal• 1)1 J I l'l+ll.i,l: AIlc(:hcnt Grnt-1,11 IloatIl.ll (I'rll.htlrt;h), I)r 11,tnlc\ A Iirnllcr. l lnni l. l\ o( I'illalurgh I:yc an l I,rr I lu>Itlt.ll, f)r. I cyrs I( liullcr: 1!ttl.Eturl:h \'clcr.lu's Il.ts(>Ital. 131. I:ubcnc N \I\cn: MoIPUt Hospital (San I lanclsro). Vnit•crsil~ of Califiarnia at San 1=ranrisco and __. __ County Hosnital (San Franciscct), Di. Nicholas Pctrakis: and St. Luke•s Ho.pital (San 1-rancisco)• Dr. l3ichard A. Hohannan. •fhc authors also thanl, s1\ \/arti.nl•t f0u\hin.ki litn cel ,oll:llktr;tlirtn in the carlt• slay,cs r,f Illr\ \lu,/\, 1,1. iJ.rn, tVi,rl"l> I,rl t~i,~p,r.Intrn~ItN .IV,~•,Iancr :nrJ t.11 \llrnlc Ilc..%lm .rrl,l h1\ A1.u1.1 N.trtl,u,r 1,11 tn,rn,nrlipl 1•Irlr.lr.rll,rtt At•ct•IricJ Ir IttrhlliclUltn •\u1'u\I tl I'1S.1 5~9E~z'9~oz . . . - . ~~\ \Illll/ constrntption, I)r0•ious diseaacs, t7cctthation :tnd O,cu- pation)ll cxl)(lslirvs, ancr, to a limilecl cxtent, cxl)aEUrc Io the tobacco smoke ctf others. Due to thc small numlc.l of cascs :tnci con(rctlt on whom v;e havc informalinn nt•I I):ttiblve inll:llclliott, IIt_r Il;tttt t)rrst'nit•cl Ilt'It, fltt tlt:lt E(Itl•• lipn :tit' in Iltc (t;Iltflr (It'ptcliminary wmtlt. /1 cli.cttssiuli of plrt:.ius slucfics c•ctnccrning this rmphasizes tltt, need fol oht;lininl; litctrc cictailed inform:#tion on siclc•.- _ strcal)) .Inol;c cxlxtsurv anci rcl,ltcci vari;thlos. Nl(•I hcftl% l1.! tI1 Illillt:lt\, (':Inrtl ill Illc Iun): o;•rullilt}; ill Iltt t(•lutrlt•cl Iti•rcI Ita\•in); Snto1.eci urt :1 It'1:ul:u hasi::` ~rt•re tlxtrarl(•cf froIn;tn cln)~,ctin};(':IC;•-c•Ontro1 tlucl), 0(1t0.%tcV(),rel;ltccl c:lnccrsconcfuclcd in a numh;-r cifcitir.~ Ixeuw<'t'tl I1)'/I :Inc1 ItJN'Oj :Irtc1_ clt•s<•rilr•<1 lar'a's•iousll'.r• For (':tcIt tllt, Its>aail:tl i•It:lrt t\':Is rr-rXcllttinr:l ill (>'r(Icr Io cltnlirltt Ilw tlia);ns/~i~ :Inll Iltc :Ilt~~. nct: ctl• .ntol:itt); ` nur dcfrnilittn of :t nonsntAl.er tras som¢onc %ttlo ha(I nc\rr sntclkcJ as m_ u:h :r. rtnc cil::ucrtc, pil,:, or s-il;ar Ix•r d:1} Gtrr a)car. i 1 hr ruoI trII1' ril Illr .ivr\ (:rnll rtt:rlihPll rllnly d.l ))t•rr iuiilvlilarrl al f`lcniull.rl I It-.IIII,II In Nil. 1'ln{. <'ll\'. .111 111 lllc S`! ruraIt• c.lv-. :tnrl /l/ of thc• '? / Il'In:llc t':I.c., I? I4

No. S LUNG CANCER IN NONSMOKERS thrt,ughe)ut the ratient's lifrtirne. The histologic type of Iun); ctrnct•r W;ts oI+t:ririctl I'ront the pathoIo)y rrtxert or thr t)ist'hargt• suntltitrry li+r cat'h cau. 9Fhost: cases in whom the diagnosis was not primary lung cancer or in whom thcre was an indication of smoking. even in the remote. p,tst• tt,ere cxe:•ludctl from the study. Thosc rcmaining in tlit- .tuily :uc rcft'r n'(I t+) as "valitl;rtctl'' rtunstn(il.crs. A c0ntrul »•a. iitutclrctf to cat'h t'a~r rin lhc basis uf" age (±5 ycars), scx, racc (with 5 exccptions$), hospital, date of inten•icw (±2 years), and nonsmoking status. Controls were selected from a large pool of hospitalized patients who were interviewed over the same period as the cases and who had diseases which were not tobacco- related. related. The distribution of diagnoses among the controls was as follows: men. 62.19'a other cancers, 24.3% benign neoplastic disease. 13..5°6 non-neoplastic disease; women, 59.y", other cancers, 14.4% bcnign ncoplastic discase, 25.`'"i non-neoplastic disease. All subjects were interviewed in the hospital with a standardized questionnaire including questions on de- mographic factors, occupation, occupational exposures, tobacco smoking. alcohol use. Quctelel's index (!tg/cm' X 10.000). and history of tobacco-related diseases. Two tiiflerent versions of the questionnaire were used o-cr the I(1-vcar lx ritxl, the first from 1971 to 1976, and the second frunt 1976 to 1980. Dif)i•renccs between the two ctues- tionn;tircn included a longer list of occupational exposures in the luter vrrsion, and a longer list of previous diseases in the rarlirr questionnaire (<litihetrc r-r+ A`ulzcrr u,)cl bi 't r)~lc~r I~ I~ TAnt F I. Histols)tiie l•)•Iv_ or I.ung Cancer in Nc%'cr Sniol.cr% and Siiiol.c•i% f,•1cn ~\?unirn (Nc,.) (C"r) (vo.) Nc%cr smok_crs Kr-cyIK•r)t tNpc I I 1 ( 1t 1) ?O ('(1 6) I.I+ylcrinI ri+l/Klu.+n+11u. II (tN I) Ir~ (I6 Large ccII/giant rell O •i (•7.I ) Krcyberg type II 20 (54.1) 72 (74.2) Adcnocarcinoma 16 (43.2) 60 (61.9) Alveolar 4 (10.8) 12 (12.4) Mixed (Krr-ytxrg I & It) and undil)'t'rentiatcd/ anaplastic 4 (IU.a) 5 (S.?) Total 37 97 Smokcrs' Kreyt+crg type 1 1187 (6?.I) 341 (S?.?) Kreybcrg type II 600 (i1.9) 279 (43.,~) Mixed (Krcyhcrt, I & II) and undif)4entiated/ anaplastic 95 (5.0) 32 (4.9) Total 1882 652 * A more detailed breakdown by histologic I% )x is not presented for smokers bccausc this informatiun was not codcd. For the nonsmokers this information was ntric+cd m:tnually. responses was smaller for the question ••D(>r.s your spoust' smoke?", since this question appeared in only one version and since it was not answered l)y those suhjccts who were 9V9EMsZoz

.._ _r• .......... . ....u~~, ?5,8'ti, non-ncoplastic- disease. All subjects wcrce interviewed in the hospital with a standardized questicinnaire including questions on de- mograhhic• factors, occupation, occupational exposures, tobacco smoking. alcohol u.c, Quctelct's index (kg/cna' h 1O.(1(1O)• ;tnd hietoryof'tohacco-r-elcttcd diseases. Two clifii•rc•nt vrrsions of the questionnaire were used over fhe I(1->rar prritlcf, the first li-ortt 1971 to 1 t)7Fi, and thr sc_cond f'r'tirtt 1976 tto 1980. Uiflc•rertcvs bc(wccn the two ctucs- tionnairv: included :t longer list Of cCcupational exposures ill the I:Iter \vrsion, :tnd a longer list of previous discnses it) tltr t•:rrljrr yuc'>ti(lnn:tiIt_ (di;tllt•tcs, };oul, llrortcltitis, rntt,Ir' Itvl><-rts'rtal+rr, aaltnta, f)lrurixy, flltc•urtronia, hronchicc tasis, an(I t(I fvrvulc~'sis) th:tn in the latcr versi(ln, which in_CIu(lcd onlv four questions on previous diseases (chronic bronchitis or cniphysema, asthma, diabetes, and t`Ic'vtttr(f Illotxl prrsst(rc'). .^I01llt,l C(In.urnl)tlltn w;ts a.axstil ill c•urrrnt tlrin{.rrx ;tnd c•-\Jrinf.cra (cunahlnrd) rc•I:ttive to nc.vc•r-drinkc•~rs :ul<I occasional drinkers (combined). Occasional drinkers were those who consumed ed less than I ounce of whiskey equiv- alents tll• alcohol Ix r day of bccr, wine, and hard liquor (•(lntlliriwl. .^Ictlh(ll intctkc was <•atcg(lricett intci lilrcc• Icv rls: (I) ncver/occasi(.+n;tl tlrirtkinZ., (2) I to 3.9 c>t./daY, and (3) 4+ or/da\,In addition, a number of questions on exposure to hassivc timol:ing wcn• introduced in an addendum to the ni;tin cfucatitlrtnnirc, in It)74, :Incf tltc ac1<lrn<lurtt was rv- 1 i.od in 1979, l'hus, Inl'rlrniati~ln ()n passive ttrtt>kint; was (Iht:rlnlEf on only a subset of the suhjects, for men, 25 of .17 cases and their niatched controts; for wonaen, 53 of 97 c•citcs an(1 their matchcd controls. This number of r,0f10nsct W;ts caht:tincd fitr those questions included in h„th v.ersion% of' the actdrncfuni, whereas the nunihcr of' I l)nc orlental rll'Jlc Cd>F N':1> nlatchcd 1o a H•hlt(• c'ontrol, two Ill,l,:lnic- .Ind tn%n oriental fcmalc i ascs l•l•r(• matc hed to w•hile cunlrols ..,, .,,.. • 1101 (c,}.I) 341 krcyhcrl; tppv rI (iQO 01.9) 2 )9 Atixe.l (Krcytwrg I & II, and undiftirentiatctl/ anaplastic 9S (5.U) 32 (a,9) Total 1882 652 ' A more detailcd hrcakdol%n h\ histologi(- Ilix' is nul I~rsrsl ntc(1 Iilr smokers txcausc this infurmaliun o•as ruN Clldad. For thro n(lllsmol,crs (hi< Inf(lrnlation was rclric'1('d manually, responses was slaiallcr for thc c)ucttit)n "I)OOs )VOur s))t)utic' smoke?'', sincc: this questi0n al1I))Carr'cl in tlnlV One VCrsi0n and since it was not answcrcd by those suhjects who w<>re not nt:trriccf, lviiicM•c(1, st•p:Inrttc'ti, or <iivnrc't•r( (tir(• T:tttlr 3). I-)ifl~rVnsrts hc•tl%CCn t'tlst•r :tn<f t'cantrlll!: MArT ;tSSt•s':(•tf by the chi-square test for indcl3encicncc?,' and hythr Man- tel-Haenszel extension tctt for linear trr-nd•" Point esti- Mates of the relative risk witli Irst-h:tsr.ef ')5',%, cmntidonce intc'r-als lvrrr v:IIcuI:-IrII lill!owint; A•ti, Ilinvrl',: nlrllllt(I." lt~~sults For the I 0-year period, 1971 to 1980, among 1919 cases of primary lunl; cancer in men. a7 ( I.9(7m) occ-urrc.d in valicl:rtr(f nilnr;n111Lr•r!:, Artt(In)r, `/•t') Ittttf, r;lnl•r'.r ('-asr ; in lv.c>rttc:n, 'J:! (I,3,O';') wrie v:Ilitlatctl iinn:nt(~Lcr t. 'I his difference in the firoporlicrn of nonsmol;crs in men and women is highly statistically significant. x'( I)= 137.2 1, P<0.001. /l1SYrtl().I;t( l'lyn. 1•able I shows the histologic tyhc of' lung cancer for nonsmokers and smokers t)y sex. /lmong male smokers with Iung cancer therr. were ncarly Iw•icc as niany 1<rsyhc,r); type I§ cases as K rcyhcrn type II (1 187 rru•strs 000), while § k Irl hv rl, I l lii I inrluJrI ulll:llnltus (•rlI. nat /-cll, %nwll rrlI :rnci lay;c lY'II Car(•Illlllllal, I~1(•vlt'I)', IyIK' II incllt(It•, at Icn4 w•:Incint lrol:r. I'.IIInrIlull:lr, and alveolar <•:uwinonl:r. ,&tF9Czz9z4z

1216 C.ANCEK March l 1984 vc,l. ;3 1'4rIt.E 2. I-)is(ribution uf tiackgrouncl Variab)cs in Cases and Controls Mcn wi.n,ca C nx` ( untn>ts _ Caxs _ Cuntiols (Nu.) ('t ) (No.) (%) lNo.) (%) (Nu ) (%) Axm ti4y 13 (35) 12 (32) 12 (12) 15 (I5) 5ll to 11 (tU) 12 (32) 26 (27) 14 (?SI Mt t•v 7 ('12) II) (17) 29 (1()) 14 (1.%) 711+ b (Id1 1 (N) .tO (il) 24 (21) l.+ul ReGgi.,n Pn+lc.6tnl l'atl+,~l,_, ){»,.h 37 2 Il+ I~ ch)ui 2 Total 35 t'r ur_ t,u;.llu,n I II 1 7 I.l-lS )6• l+ 20 l otal 37 (X\'utl.lln+n.ll fIJIU• Ptu)r}.yroj( l: Sl.dkd 6 Scm~.ldlcJ 2 ll„~1,II.t1 3 Ilou~a.afc 0 Kctu~t(;uncaipla~cJ 4 luwl t) 17 97 97 0 ) 5 ((4) 27 (2n) 34 (36) (4al 1.1 (•IO) 11 ( 1') 16 (),S) (J-1~ I.t (1~,) tx (40) .`b ('3) (6) 3 (9) 0 (0) 1 (1) 35 96 96 (s4l a (In.l) 18 (P,:) :v (;•) 4) 11(, 1) tl (29 7) 21 1) (•lx I) (2L(+) R (2I.6) li (15.5) 15 (15 5) (5a.&I (2 (32.4) 16 (17.5) (5 (IS.S) 37 97 97 (W~) 14 (37.S) M (8 2) I I (11,3) (16 2) 7(18.9) 26 (26.8) 35 (36.1) (5.4) 9 (24.3) 6 (6.2) 6 (6.2) (8 1) 2 (5.4) 8 (8.3) 5 (5?) - 0 38 (39.2) 28 (:8.9) (S.S) 5 (13.5) 11 (11.3) Il (124) t7 9) 9') arliont; Icn)alr .n)ohcrs the nucnbCrs were nwrC similar (3-i 1 versus 279). This r1i(i~~nh~~ hold for both )Err'.y1>crt; I and fErcyhcrp, II ty{~(tss tl)c. n1C:ill age for Kr-eybgrg I(ind l:rcybcrg 11 IunF canccr in mcn was 52.8 and 53.6 ycarz, rl-snective.ly, whi1c ill \%•o)r(- n IC.rcytlerg I had ;i Incr.ln ,(re of 63.7, and l:rcyheOp, II Ilari a mean nf 61.(1 yl'arti. Ecluc•uiion Kreybcrg 11 cascs at){)carcci to Iic mOrc cdl'catcci than Kreytx:rg I cases in both scxl;s (d:)ta not presentc(i) C.'lL.1L'-C(JnlrUl (.~Utkl/1!!)'[.FFNts There were no diflcr-enees in male cases and controls by religion, proportion of forcign i)orn, marital Etatus, and residence in c•Ililclllcuml, ct(Ic)Icm'cnce, :In(I attltl(I)c)<)c1. Malc e.>,x;s wcrv. l)Ott',r ctlucatlcsa (i'1'h, Of c.l.ra I)ac1 f;One beyond college compared to 33%, ofe:ontrols), and a higher proportion were profe- ssionals (60% of cases compared to 38% of controlY) (Table 2). These differences did not reach statistical SiKnitiCtlncv. I'-c111Ctlc CasEs and ccrntrols (li(t Ilc)t tlilli"t sil;llilic:+nlly on proporiion of /i)reit5n born, ntari_t;ll status, education, occupational status, or residence in childhood, adolcs- cence, or adulthood. There was a nonsignificantly highcr proportion of Jc•wish women slmc)ng cascs c(>'nl{)arc-d to their controls (40% rrrsu.c 25%) ('1':rhle 2). In huth c:.)ses and controls, the proportion of urban dwc:llc:rs increased from 'l0c#'o in childhood lo 80% in adulthood. tfi.crorv of prer'iclus disrusrs: No case-controI difli;r- enccs were found for history of chronic t7ronchitis, cm- physr.nla, ciiabc•.tl.•s, astllln:(, {rncumc)nia, or tlypcrtcnsiOn in males. In fi-)ti):(Ics, tht•rc. wcnv. similar findings. rxccI)t mc)rc• fr.malc casc•s had cl prr.viOus hixtory c)I'pnrll)1)(,nia r,.'r I 1 than controls: Ib/4O caws tx•rs(t.e 3/38 eontrt,k StgEZZSZOz

-. 1,,.,/ 13 (13.5) 11llll( 37 37 97 97 ~1\YUt1.,lh.n.1/ ~Lllll• (w.) 14 (37 .T) 8 (!t ~) I I ( 1 I 3) (I~:i 7 ( IlS.y) 26 (_'b ii) 35 06 1) !:rnu.1.~IIrJ (~s) y c_'-g 3) 6 (6.2) t (C"-'1 t In.A~IIrJ 3 (R I) : (5 4) 8 (8.3) 5 (5.2) u 0 3ri (39.2) 28 (2:i.9) R~'l~«•~l; unCmpL~~cJ 4 (; S) (IJ.5) +I (111) 12 ({-'4) tuul l! 7 91 41 arttont; li>ntult• stltukrrs thc nunrbcrs Nr•erc niurc; sintil:tr (34 1 >ersus 279). This dillcrc:ncee is statistically significant, X=(1) -- 25.91, P < 0.001. Among male ncver,smokcrs, thctr cverc• 11 K rcytic, ly: tvlx• I l•w.cu.c 20 K rryhc.rt, tytx• 11 casc., %%Itllr ;ltul>tt}; Ir(nalc-., thrrs' Nvcrc '2(1 Krc:ylwr?: tylir I t•e•tstta 12 KI'cyhe'rl; ty{x 11 cass:s. Althvubh the numtk:r of ni:rle nonsmoking cases is small, thc: difference between men and women is statistically significant, XZ( I) =- 3.y(1, 1? -(l (15, Uurthrrniore, thc diflc•rcr+cc hctwecn the t.rupottwll•. of hlrNl,cl1; Imlli K+ryix'It: 11 in t',evt•+ Nniol.cr. c0n)(>arc(i With >nic)1.c')s is statistic';+lly SignilicanI in both sc xl•s (for nicn, X=( I 1= 10.54, P< 0.005; for •,.•ornen, )( '( I i =- 3•5.4fi, /' <. U.001). "1'ahlc 2 gives the age distribution of cases. tvSalc cases are significantly younger than 1ctliale cases (X'(3) = 1 1.30, P< 0.025). The mean age fcx men was 53.9 year-s (SD (Stans.lard ,ic,vI:Itit>tt) 14.3) compared w•ith t> 1.0 ($D I ).3) for wolricn I I+)t Yuunt;rr age uf nralc• c;t4cs al)l>cara to ,tl:rtitat statux, education, occupational si•-,,Is, or rc;tidencc in childhood, adolcs- cenc€, or adulthvod. Therc was a nonsip,nif(ct+ntJ~~ hig.hcr prcip c)rtion <)f lcs•i.h >v(rntc+i ssnlcrng c•:tws vlrt))I>ar<•<f tc) their controls (.10'fi. +•er.ctrs 2.')`Y,,) (T;tlric ?). In 1>uth ca;cs and controls, Ihc I)rlapc)rticrn of urlratt dwellers inc rc::+tic;c) from '10% in childhood Io 8U1tl, in .ululthtrod. flietttrY of preriotts disertsr~Y: No case-.c'ontrl)1 cfifii~r- enccs were fe>uncl fcrr history of chronic brcancltitis, c(n- phvsc•.I)la, cli:(h,•(ct, ;(sth(ita, pru:unimui;+, or hypcTtcnsi0r-1 in malc?ti. In fr+)I;tlcs, (hl•rr: wl•rr simil,•u~ linctin),s. c•ac•(.l)1 rntorr frin:+lc c•:Ia•s h:+c! :I I)rcvicnrs hw,tcry of lanc•un+ctnia than c:ulitrols: I(1/-1tl cases v<•r.stc.% aj3}i c'ontrolt (X~( I) = 10.9, P = 0.001). QueINlet'.e irrlrt%-: Quciclet's index was calculatcti tiir su'•llCci'.~~ . it;hl 5 yvars pr'ir>r• 1rr tli:+r,noris fcn 72 rrulll <amrs :lilcl tlu•u Ill:+(c'lu•cl l•i+ntrcrk ;+nll li+t .`q1 fc•ntalc <•W,r', alud c'ulltlvls on wlm+u tl+iti in1i+rn+atic)n w:+a :+v:+il:lblr. No ciifli.rencc was scen t>ctwc:r.n caws and corttrcrls of eithe; sex. Alc•.:!rctl: Nct si},Ilificctnt difierc.nc.c.s in alcc>hol in1:+l:r: wrrr fmlltll hc•twccn r:+scx :+nt1 (•o+tllcals of c.ithrl st'a. ('1r•(':111otirmi11 c.tttuxurr: No (lilli:rc:rtcc 's Ill c>k'c+ipalion;(l exposures were cit3sc:rvC<1 t)etWGCn IlaalCe ctiscs an(i contr<)1 ;. In fgmales, the unly significant difl•crenccwati ttiat 14 cases rcp©oed working in a textile-rclttted jph comhared to S c•lr+t(rols (rvl:ttsvcc t'isk, Z.I(1;')S`X, <'onfittenrt• interval 1.1 1--?;.04), Uf,thr 14 feni;tle c:tses, 2 wt-rc:ctiaSnoscd \\ilh !`rcyhcrg 1, I 1 with hreyberg 11 and I had mixcd-.lyhc lung cancer. 1=or those cases and controls intervicwcd between 1976 and 1980, information on the duration of cs/zo;.urc to <)k-cuh;ttional and envirnnmrrit:+1 sulrstanc•r...• wak :(V:(ilahlr. I'hcrc: wcts no <iitlerk-nuc: in the ntr.un nuni• sv9Mzszoz

h Nb. 5 LuNe, CANCER IN IVONSMOKeRs - ,l`ahut tr"rcl tis<yndec 1217 K.-r rrl' ~t':u% ul t'\Itostlli' Irt It'~IIIt',rt'Ia(t•tl ttibti (10 1'~:IrS) ~tf ~-:t>t'> atttd t-t~rttrt~l~ i\rnttnF, the c cru's. Etlc ~tK'\'illt- ut'- cupatit~ns \\err thce fi~llt~wing: one srarttstres,,, two ~lresx- mal:rrs, one sewing-machine o)xrttur, one :tsserntrler and varrtt,%irtder• one dress-shop .s•orkc-r, two salesladies who had tttinr litt'tor\• worl., one app;trel ntanufaCturcr, unt' cluthint; put'ker. unt' typisl, one waxltorrt(r/hcsusc k\'c(K'r, one botal,l.ictkr. :tnd one htaust'witi1. Anurnt: the 37 nialr cases only a tcw (5) reported cx- - pOsurV. tt, substancra of Ixotrntially etiologic interest. An clcctronics cnt;irtc'rr had 35 yrars ttf•exhusurr to clcaning chc ntiials: adi.ignt-r had 25 years taf exposure to chern-% rt.alx and awitls ancf 15 yrars t,f'rst,usurr to plastics and l;lui~s: ;t dirrilttr of s:tlcs filr :t t-hrniical cort-n>r:ltion (ct rhr-ttlia) had I_' ycars ttf rxposure to cltrttiic'als and ac'ic1s; an upholsterer had 30 years of cxposure to ashestos. rub- brr, and solvents: and a machine shop attendant had 37 \cars of cxposurc to mrtals. ):rease. arui oil. Artiont; t)tr Q7 li'nistlt- t:tsrs in :ttttlition to c',\pu%ur'r to le.Stilc \vurl, Ic'{iortrd h\ Ia, t'ew rrtwrtckt other cx- fxt.ures. 1'he assrntblcr/}arnilvincirr who reported rxpo- .ure to tc xtilrs also reported csposure to metals for 28 \rar.: :t machine operator had IO ycar~~ of exposurc to ntctala: ;in :t..i.t:tnl trn-ifit':tl trcltnicicln had 10 ycar% of i xG1osurr tt) chemicals and tt.'it1s; a social wurkcr had 5 sears of exposurc to metals and welding; an electronic prototype tech nician had 14 years of exp_ osurc;. to chem- it-als and :tcids, metals and solvents: and a chambermaid had 23 \r.us of exposure to ctnintonia 11'c looked srlsaratc11' at the stit;tll nttnttkr ufcttst'.ti who developrd lung cancer younger than age 40, eight men and si\ women. The occupations of the men included an accounting nrafessor• an accuunlinn o1f•r4• h-,.+ I nM 1 ). I.jtr"•urr to P:tscivr Inhal:uion ,1nton}; a Cuhcrt )pC , . . I( 'I I t . . .Ik ~ rn, . nliu ti Men - \\'omi-n -- C'asss Controls C.'ascs Controls (rJU.) (7t•) (No.) (T) (No.) ( ; ) (Nti.) (`~ ) At honii•• Yrs (r 5 14 17 No 19 '(1 37 :1( 15 25 53 53 Totul At wurkl . 18 1 1 26 31 1' cx 7 14 -) 7 )? Nu 15 25 51 53 14tr:d , (P < 0.045) Spouse smoket €ve r 5 3 13 1.5 7 7 II 10 Ncyri 1'ut:rl 12 I ' Current r<•xposult! on a regular basis to family mcmlx-rs a ho smo{,r. t Current r:xposult on a regular basis to tobacco smol;e at wort:. t Spouse's currenl or past smoking habits. reported that tht'ir wivrrs smoked was it.lentical, 5 ()1' 12 in both groups. Ir7 both groups the w)ve s had smoked for comparable periOds of time. N_ o differences on exposure to passivc smokin_ g at home or at work wcrr fitnnd in wonaen. Ilt rsf 51 c:rsc•s wrrr exposed at hunrc , t,rttp;trrcl to I'I t1f.'>.i r•ttntri>Is, srnct 26 of 53 cases were exposed at work comprlre.d to 31 of 53 controls. of the wpnnen \vho were asked ahnut their 4s9EZZ9zoz

tct tC.\tilc %%tlrk rrtutrtrcl l)\ I.t• li•w rt.•'.Wlctt otlrcr t:r- fxlsures. The as.c-mblrr/varnwirtcic•r wliu reported expo- sure to tc xtilcs also reportrd exposure to metals for 28 \r;tr.: a nt;tchinr operator had I{1 years of exposure to ~nrtnl.. an a..i.laul nt(•drt':tI Ick ttnici:tn Itacl It) vrarx ul xtttc' I~r t'Itt•rnit'als atl~t :tt'tcl", a s~~t'i:tl wurl.t't Itatl 5 ccarr of exposure to mCtals and weIcling; ctn electronic ic prototvnc technician had 14 years ctf exposure to chem- iCals and acids, ntetals and solvents: anci a chambermaid It:ttl .'. 3 of c'\postttt• to crnttti0nitt We Iool.t>d srl~:tralc'I~ :tt tltc >nt:tll ttutttlt.'r ul'C:ta's wItu tlcVCI0t1c•ii lun~g cancer a'0unkcr tltan age 40, eight men and si\ \~Omc.n. The occupation, of thc men included .tn ;tictluntint; profi-ssor. ttn aicilunting clerk (.vho had Ik•c•n a tc'a,'trt'r lor I I yr:u's). a nrurosurgrort• ;t stock Irattcr• a postal .crvit't• clerk, a I:Iw studcrtt, a tialctman, and a.c:ll-emplovcd presitlent ()t'a 5ut)pl\' company. None of the nten roptlrtcd any cNt)Osurcs. 'Fhc femalre cases inCIudCti t\.0 Itousr\6ves, an assistant rnanager for the A mc-rir;tn Automobilc Association, an electronic pro- tut\ f~r rnginccr (mcntioncct ;thca\ r). :t tc Icphonc operator, and :t high schtxil teacher. C)nl\ thc> clt•ctronic> prototype c'rtginrer reported an>' rr;pclsurrt I lir tiitilr-ibutittn of his- toIot.ic I\tsc's ;ttllttnt; Ihesc 1'ttunZ;rt k';tst's did not at)I)Car to tlifli`r frunn that of all ntansmokint; cascs. f'uccir•e rtrlicrlurion. Of the 25 mctle cases ;und controls tslto \\c_'rc• :Itkrtl alx)ul t•\t`10turc' lt) otht-r Ix'oplt s t'i,r,arrttc .nio},c• at htttltc•. si\ ni;tlc ::t.c•. rrPirrtc'iI having bc•c•n t'x- {10srct compared to S c'ortltula ( F:rhlr 3). Figlt(ec•n clf' 25 cascs rcfx)rteti having lken exposcti to cigarette smoke at work compared to I I of 25 controls. The difference "lust .tati>tically sittrlilit•ant (1' -- 0.0 5). Mantel extension Ira fior Itnr;rr trrnrt tn tlrr I'rs•itu('nrN 44, c'xpo"utr (G)ut Ir\els) in c:ra's and con(r0la ~;ttra a clit-mluart' uI .' Kti, 1, < U.(X)-S. The numher ol- nlale Cascs and controls who i'sHal t 2 I? ?.t ~5 ' Currc-nt exposurc on a regular basis to famill mcmlvr% who smoke. f Current exposure on a regular basis to lohaccn smnt:e at work. r tit)ousc*s currCnt or past surcil.inK hahils. rt•t110rted that their wivt:s srtltlkctl was identical, .`, tlf I~ in both groups. In both groups the wivc;. had smohed fclr comparable periods of timc.. No di(Terences on cxposuree to nassivc smof;inf, at honic m ;tl work wcrc liitrnil in wonrrn, 16 (if' S., i';tsrs \vrrr c•st>usetl at Itunlc ,~nlllttrrtf tt) I/ cl/'',.t rotrltol., and ?.0 of 53 cases were exposed ~tt work con,parcd to 31 of Sa controls. Of the women cvho were aslccd about thc.ir spouses smoking habits, no c)ifi'crences hcawecn c;tscs and r.;ntt'ols were !'nttttct in 1''1r tarclport:4,n trlln timrlkr.ti, 13/24 fclr c•tse!: vr•rl us I S/.' ', f,lr control::. lct;;rin, )tarr. of smoking in the cases' husb;incis did not riifli0r from yearF of smoking in the controls' liusband:. D1Scllssfon Due to the 1?ov,v,('trl rolc• of smoking in Ihe etiolo};} of IunF, cant•er, otlivt risl, factors ran I)rnl hc- ttu(iiect in nonsmokers with :onfirtlictl n<1nsnioE:in); liiaclrit•s. 'I-hus, a key feature of this investi),;rtion is that in order to "v;rl- idatc" the. diagnosis of pt'imary lung c;lncer (obtained from tlic discharge suntm;try or th(, hatholor} r-oport) and Ihe nonsniol.infr, st:trus ttf all slucly suhjcrts (obtained irl the original intc>rvit•w), we went Intck- to Iha hotpitttl rec:- ords and abstracted information on diagnosis and smoking history. Ifthe chart indicated that the patient had smoked tobacco at any period of his or her lifa. the person was vs0ntlrcl Irotil tltr• titud\' In Ihc. r;u'. in..l:rnrv Ih;tt ncl tttrntiort ul, .nrukurts. Iliaurl• was frluncl in tltr ('IItr11. Ilrt' hatic:.nt was inclrtcieci, Of'Iht• 156 c;tscs nf lun); cancer in ii Tssczzszo~

1218 CANE't:tt ,tlccrt lr l 1984 our computer ftte of self-reported never-smokers. rcview ttf thc- hospital ch:tr-t revealed that 13 werc artt,:tily srrtol;cn t,t h;td .rut,l.rcl at suntc• tisttr. ctnd r) %.c.Ic nut ttristt;trN, lunhian~'rr~. (hrsc "ta.r.wcrrr~t'lu~lctt liurtt tltranal• ysis. Cunlirmation of the diagnosis and nonsmoker status of the controls was carrit:d out in the samc way as for tile cases. For none ctf thr controls was the self rrported nortsrttof.trt}; %taUs• itsntrsuli.tccl h~ ittliMrttatii,st itt tile i1,:ut 'f_ hc• finkiint, that tttcne cascti gave a conflicting response on .vhrthcr or not they had ever smoked than controls ( 13 ctf 147 primary lune, cancer cascs ectmpnred to none ril, 1.1.1 coniUolz) is ttf si}:nificattce. '1'1tis sut t;c•sts that sctmc Iuist; cancer c:tsrs tc'rsif tu tlt'ny u snts,l.irtf: Itistttrv_ tttutt• thall illntrUlS N'1llt nllll-10bilCl'l)-rt.•l:ttt•t1 tlistusr~. In a stutly of'thc role of cig:trt•ttc sntoil;ins; in lungcanct•r, such denial t,f'c'it;arettr cctnsttnttttittn or ustttcr rr{tttrlint„ which tttay also t:tkr {~lacr. would tc.=nd to reduce tile estimate of' tile relative risk. In a stuciy ctf lung cancer in nonsmokers. thc inclusion of casrs with a smoking history (ntisclas- sitiratictn) would also rrtlucr .t•r'st><'iatittns ttf tile <iise•ase with other risk factors. Although we attrntpteti to eliminate all smokers from - among thc caks and cttntrols hy using a conservative definition of rtonsrttttkrr :Ind by t•m-lu+lin{: :trty subject ~~ith a ltiaory uf' .ntof,ittt, t•itftrt rtt thr ~ttrrtitiutsttaisc or in tile hospital rftart, it is possible that some auftjcc•ts who - reported nc:vcr having smoked actually did smoke at some time. The current stucJy confirms earlier ftnclin}s that among lili>Iont; nontintokcts lung cancer ia rxrt•rcfint;Iy rarc, and that tile ntorr conservative the detinition cet• nonsmoker and the more detailed the smoking history, the lower is the proportion of nonsmokers found a-~- r,-~ ~' -- ratio f•or lung ;'ancer is ?A," and thc ntale-fer,talce ratict :sntctn{; all lun{; caitct•r casrt: in nttr filr is• ( I'! I')/7,l'1)- I ltr Iast:rr nuntt,rr rtil' suttt-.11s4,t.in1; Nvontr,t \\itlt litrt}; t':,n cer compctrrcf %.•rth nonsntuf,in{; rnvn ra I>rrsuntattly tlur to the historically higher proportion of nonsmokers antonp, wornen compared to men. Doll found no differencc in tile age-specific death rate from lun}; cancer ttntctnl; ncsn• .ntttkinl nt:tlt-s and ti•rtnalt•s ' tiinularlv. ( intiinl.rill li,uncl ntt diliErcrue in tile abc-atlluac-LI lunl.1• r:tnk'vt nuut:tlity rate fbr nonsmoking men and women. C'ct.w-Ci»tfrol C'ct»r/~urisctns 1'rr•,vorc.s. c/rsr•rttc% Our lin<finl; Ilt:rt li•rtt:tlr i':r.r. h:td a ltitater' lcrttus•nk'y ttt' ttrc•vious lu.torv ttl` I~nruntc,sti:t rontftarcd tr,t contrctls is diflicult ttt intt.•rpret sistcc v6v do nctt have infornt:ttictn on the age at cfiagtttsi, ctr on thr duration of pneuntuni:t. Occ'uluutiotr_ l:ctrlit•r case stutlies of lun{; c:tnct>r irt nc>n- smttkers have included occupations in malt•s with ex- posure to dust and/or fumcrc• •:r c;:trfv.ntt•r, :I joiner, a fittcrI and :t flour sttillr.r :ttttttng lht, 7 nt:slr vasc•s in i3u11's study:t two painters, a smeltr:r-, a hlacl:tmith, a gasoline truck driver, a gasoline and ctil delivery man and gas station attrndttnt. a cattinet maker. :t sau•n~ill %vurl:cr. and :tn rnt;irtrrr :Intrsttt; :'O nt:rlr• c:.r,c••, irt \\'5•ndrt •. autly:'~ a ftlusttlx r jstc,tsttlitlt t:tntl :rst :tutrs hotly suttt ti-rtttt•s rr pairman among 8 ttiale cases in tile study la\ Wynder and 3erg.a Among fcrnafe cases, the ttccupatittns were less suggestive of exposure to inhalr:d substances. These studies intervirwc•d small nuntlwrti <yFnonsniof,ins casc•s• antJ t1ssS nttt 1tt:rkt. u.r• ttf :r r•rstiift:rri!,rtrs I;rrtufa. Our findings oftl statistic_ally significant threrfiold (•>;ccss risk uf lung cancer anlt)nf; women who rennr+.•A MqV~~9~'oa

tn the Ft0shital CIt;lrt, it is {)Ossi`•'e thclt sunnr.ut)jrCts who report~.'d never hat•ing smoked actuatly did smoke at sontc time. Th<<urre nt stucfy c•onfirnts earlier rinciinty that antonf, )ilelctul; n<tnmtlcrl,rt. Ittnf, i:ttl<'rr ix rXc're0tnt-,l~ rarv. anci th;tt the more consc:rvative the definitiun cit nunsntuker and the more detailed the smohng histoq% the lower is thc pruportion of nonsmokers found among lung cancer raws. I lli~lc~lcr•t;i< Iaytc' As found in car{ier tiludies, Krc:yherb typr II (primarily aC1enEtl'arcinoma) is inore eontmon in nonsmokers with lunt;can«•r than in smukcrs and, in ta<tth e:r„ults. Krrylx•rft tytk I I is itture Coitintcen_ in ..•.unirn. 'l lic f~c'rc ent,tl;c a u1- rttinsrnoking Cascs with actrnoCarCinc7m:r in ctur Studv (4a% . or males, G2"i, u( Ihniales) ar<• in .:lusc abmentent vvitli thEase front (hC American Cancer Sucicty's prt»hrC- tke stydy (-1(,^G% t>f males, 59'n, or fcmales, f.. (;:trlinkcl, {iCrsiinal <ommultiCatictrt, I9ti?). Irt VieW o!'thc•(jillirett«s in rlrsign and meth<tci ctCselreticin etf tiuhjects, this :tf;rer-- nlenl suggests that these Ixrc-c:ntal;es nia)' be rrf71r't'sVrttatit'e or nunsmtlf;inj; lung c'aneCr cases gener;tlly. ,S'<'.~ Kulro In Omr n0nsitn<rl.inl; c:rses there strr ?.ft ttn= a< tnany WalrS st. itt:tlra, r% t'n lNIu};h (ltr tttali' li'utale' incrctc'nc•e ..... . , , . a I~funtl~< r/~tt .trn/ittt t:cnt) :~it attt~t I~~t~fy an~t li'iutc-r rc pairman att tg 8 male c: rses in lh<: slu<Iy I)\ \1'yndrr and Herg.•' Anyong fi:m;tle case4. thr oCru{)ati<tns were less sttggcstlkT or c?xposurc' to inhs.tl,:d suhst;ln<'rs. 1 host> stu<lic•s intervic"'t•ci small nunihem ~tr npinsntol,inr <'atrs, ttnd did ttot ttr:t6c' ttS%' uf*sr voit+lt:rtv,41tt t;tou1t. Our findinZ2s ufa statisticall) si}tnific::tnl thr0.0,6Id c•xress risk c>l-lung canrvr anictnf; \vctnien wh<t reponeci h:tvirtl, workc•d in the tc•xtilc iniiu5try is of intew. I)ull, in_ (titi stucit Of lurnf;C:tn(>Vr:tmonf; itrtn:ntrtl'~ r:. littsctc<'upatictns of rn,1rc tlran 1yr•:rrt <Ittt:rluin itr / itt:rlc• trn<I •1O li'nt;tlr. lung ~onc•er cases. Uut of 3 1 wonien whu had N-cn eni• ployed outside tfie how 3 had wor-f:4d ;ts srtmstrt>sst-F or dressmlkc'rs.' Howr\er, there is no cle:tt' rr.-I:rlionsltip i+l our d:+ta hrtttrc'n <1_ui'tttion caf (•.\tto`urc' :rncf ri!-,I: taf' tiia':tsc•. Thr moan nuntbCrctf'V<'ctrtictf4xp<t:ur<: w:.t; thw. scrnnc• litrc'aseti ,tncf C0nttolS. Most imlzurt:tntlv. it is not elc:rr that there is a sint,le etposuri or f;roup of tahcr:ures that all Oftho work<•rs irt lextile-rclated jc.ths have in common. Furtherntore, it shctul<f h<: rnipltasizecf 111.11 uur or- c•uhational dat;l are linjitrcf sinre~ thert' was room cmly to code ttnc• cu-rupation•-th_a1 ctflcingest <furutitm-anct two c.•xpcisures. Ooctrtlatictn,ll anci en4•irvnntontat expcttittrc•s t0 specific substances were c>htaine<1 by :tsl:inf; the subjc'c'ts whether they had ever lxcn exposed for more than a)rar to stnt' of a list of suhstanr'<•t. S<.-1f'-reportt`d crpcrsurc's uf' tltis f:incl are .uQvt to inli1rna:lti<tn lti:ls tiin<'<- ;tW:u'#.,neS.% Of att-lt r\poatrtr C0uftl be rxlue<'tr<I Io Var ~v~ itlt tlw in• Mqf:zz92:oz