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1Ew".l2 115 : 111 V301 , 402 ' 021':: .; NC:1 • f t,I C EnvironaleatYl Tobacco Smo'lt'e', and Lung Canoer' Risk In Nonsmokiag , Women Heather G. Stockwell,''ALtarr L. Gol,dmn, Gary H: Lyman, Charles L Noss, Adam W. Armstratg, Pbtri!cia A: Pinkham, E1'izabahC. Cattdrlora, Marcia R Bkusa Backtrnatsle Expoenre to envlren• meatsli tabacesi aaoka (p'art.e aatok+ lolt) ku been sau.etMd ta be a canee of'Ituts, calism, altbotyh!.arlvy apide• taiolatic attidlea 6a.e produced In# conaliutenr rerattn P'urpoaet We condueted an epld.muoiogic eaae+ control! atudy to /aaaet; ths relhtion+ shlp bet4+een, ezpoe.rc to enviro'n4 meataill tobacco trtaoike and 1ivinQ ancer' riek azotaa, women wio have nemtr'anoked (L..,,hai smoked for a, total of <'i monthe or having >Ilaoksd <1tDO1ctttytrettxt ia t2delr Ilfe- timee)'. Me[JioLt:' Caue patients (in • 2110) were women witdi hlrtoioslcally' coaldtm.d prlmi ardnomaa of the' lutt!g' who ware tltei nortsmokars, They' were id.entIIaed! tfiroegh i Loepltalc tumor reqietrbcw artd the FloridaiCan- cKr Diata! System o~f! the! StatewddtCancer Reiistry. Cominunity:baaed . control women (a  301') were silso l'Ifetiinx iaonsraakart a'nd wKxm ldeoti- fted thro.=k random-dlptr dialling, DRtadld' on childhood and adaltihood' ezposares to envlronmeatal tobacco s¢nokcwere aecertailnedl tli!ro!uQh iuWr.i..., .vtth tb..tud'y parrLdpa,nt; themselves or wit!hi surro4a't'e r'e. epondknna- RLt1ia, were calctilaGed' in ur¢ta of emok.6-ye.n, diafiaed as the sum of the reported years of'a:poeure to d"ate emokx frorn each emokxr. REPORTS In the aowaholtl. Rtrii The ri+k o1. Ittas cancer more thae doubledi for women who rep,orted 4'0: er more smoka-yurs of ho.echold expeatre dorlitg adttltbood (odde ratb [OR)  2~.4p 9'Seli eoafideace Inti.rnal [CI} .' 1.16.f' :3)!.r 22 or tnort amoka•ycar>t of a:poaun durlig childl}ood aad ado- lie.ceacc (OR  2.4; 9!f e1G CI a 1.I65.4)1 Rlalts were highest fbr aon- adeaecarelaomt lpng canKen: al- t6oi 'modeatal+evatlbae Ih riek ware alao observed' for adMaocarel.omu. Whete a aarroga+tei reapo.d.at other than the patlmt'e huaband pzevlded'. Infbr>oatloa oa expoatrss tberiak estl• mata i Mere conaitlertbl8 l.rrtr. Coa. Clatdo.» Tbesle nadliDje tnggeet thac ltra`.term e:poaare to enviroeateatal tobacco ttaoka facra'eea the rlak olf lung a71C!! In wolbeniwko haveti,erer smoked. [j1 Nati Caocer, lnst b4:14't!7- 1422, 1'9921 In 119R6, reports by the Surgeon Gen• era!I (1)~ and the Nationrl Academy o'l. Sciencos (2)' concluded that tnvo'luntary smoking can ausae' lung eanc+er' ini non- smokera. N(ors recendy, the NafSoaat. I]netitutt: for ©ccaper.onai Saftry Q:nc Hcahh rclt:aaed' a buliletin thu' reachcd siatilar cont>lrosiona' (3). Several addi- tional studlea have examined the rela- donabip between environmerwa1 tobaccv' smoke and the deveiopment of,luoa car,- ceri in nonatnolccrs. Ln 1991„Fontham ct al. (s) repotned'c thc results of tlic C-st 3 years of a large: multiantered siudy of lung,carxer risk among fcmale lifeuic;c nonsmokere. For nonsmoking womc, living with a spouse wno SttlaJccd, trc-e waa a 50% increase in risk for develt>p• ment of lunQ,ide'noearcinomasg in aod:• lion„ there was a stgnifleint incrcase m, risk for nonttmokinQ women exposed ic environmental tobacco smoke a',t wurk or during eociat activities, No asocu• ti:on was notedfor nonsmoking womcn exposed tio en'vlronmcntal tobac;.oo smoke during chilUhoo'd. In contrust, lanerich et aL (5) found that expoxure! to high levels of household stnoke duringg childhood' and adoleacextct doubtled thee risk of lungcaneer amona rnale and' fctnalb nonamokert,.+hereai expoeure to smoke during adulthood was aoc as- sodated with an excess nak. Ottur-au- thori, (u5-d)i noted an increase :n lung cancer r1Yk among the offtpring o'l smoken, but their study populations in- cltlded few children who were rxtt ciga- rette aIIlokCra tbemSelveb. The cautent study furrthor explorex the effect of envlronmental tobacco saaokc and other riak factors for Iung cancer on women who holvt:' never smoked to- bacco. P'at:ieats, and Methods A po'pulittion-bar+e',d caae•contrmt study waa conducted in central Flonia>s to examine the uusea of lung cu,cer' in nottsmoking women, Women were elig• ibic for inclusion as case patlenu if'they had a hiatologica~llv con'ftrtrttsd primary Rocui..dFtbtuaey:4;.:'ti91;.rwniad11u. :. 1m; am.pud lune 5, ;99"t. S'upportcd b¢ Publlc {oulth S.rvics pem CA-45S1J-43 from the 4umnai C,tacenlnn5t,tt. `fatlonal Inuttiutck ol' Hltrl:h4 @ep'arzneat o*' FNaallbirnd ttumaa Sorvicoc. H. 01 51n,ceweh+ A. W wrrnaaroa, P. A Pintibam, E' C Gndelotc v[ R. Bruts ;Dee~aar.- ^+uri of F-0idemtolo(,y and Biortaacks), A. L Cunldman.,G. NI I:ymun (Deoartm++t ci L,utmv Widtdne. CoIN!ts of 4ltdtelaep, C. Ii N7s (iDc- pa,nmea of 2rvi'onmcrvlt and Ocm+cci:ont.. Hcallh; Gflleac of )'uNPc H.atthp; Cnncntrv o' Sinrth Florida, Tampa: F+a. 161 Ilent all uf the 'naptuln to tee encs %Fi ;iaintctpatad in iht.vudq sno.UU Stau~d:Caaicar R+eiury,. DaPaAment,cfFlealth rtd!RaLZ7tituu+c ]ervtt:us: Tallhh.aaxc. fli . Z1hc ua:bcrs. u.arnri fult r.rpontib4lily fnr thc sn.lyrMS ynd irtc:-oneta. uon of tl`q d.u 'CamrzpoadK.oi mr. Hculhen 0.. StOcFwet:'. SnD., Depetimcot,ot flp+ocnuology u+o Blosucr uca, Cc11cp. ot Public Fk!tliM:,tDnivcrsny & Siour~, tonda. Tit.neGtt. ftL t_to::.i6tl:l voL 34, No. ItS, Scptcmtxr 16'. 199Y' ~`~~^:

. 1418 tri,9i 1i519',2 15712, ' 12~w 1 -iu2 li'212 carcinoma of the liung (internartional Cliaasif1cation of Diteancs for O'scologycodea ll62:2-1'62:9) that was diag7tosod betwcea April 1„ 1987, and February 281 I991, and'If they rwsidod at,the time of dlaxnoslit ln a 2b-county area in centrall Florida. These women were Identified through the tutrtor registriea of area hoa- pitali and the FlotidY Cancer Data Sys- tcm of the Statewide Cancer Registry. Control subjects wera cotrttmunity baaed! and were identified through random- di'git dialing. All ease patients and con- tnol stttijects were 1'ifetlme non:mokers,. def6ted as having amokad fiu a ttstal of leq than 6I months or having emoked'. lio-as rhan 100 cigarettes in their life- times. Tlie smokitu statua' of' potential c,aaon p.[icttts in the study was caoflr®ad at't several etaSes:: Once these indiividuala' were identif cd by their hospital or the' Sutewido Gneer Ragistry records, their' unoking' ttatua wsn conflratedl whcm. their pbytticiaa was contacted for per- miasion to ihtarviesv, lugrin at the tlttx' of ln'itlJconiita rvli~p~i~ni or aftt of kin, andl finally, at the commence- ment of the isterview. In addition, the' intesview tssttttlised questions regarding, experimetltatiiDn with tobacco„ designed I to elicit in a nentrnl nnn'ner any prior' undisclosed tobacco uce, Any' potential cue patisat'whore smoking atatia,t could not be confirmed was excluded. Of'f tht" found to be elijiible, 83% of'the'f case patients or their next of'kin agreed to be interviewed. The smoking, stattns of controt subjects was dcterminedi dut- in'g random-digit dia'lin'g and verif3ed during the interview. Trained interviewers interviewed'case patients and coturol' subjeca either In person or over the telephooe. When'nec- enaryn quesdonaalres' wert mailed. Of the' case paclent Ihtervicws, 4'11% were obtalned by in-pcraon contact, 51% byy telephone„and 8% by mail. Of the cnn• tro'1 subjea' interviews, 53 ,896 were' otN trined by in-person contact, 45.9% by telephone, and 0.36L by mail. Informed consent' was obtuned' from the eue pa- tients and cmmtrol tubjects prior to tha interviews accordlhg to the guidelines of the University of South Florida Insti- tutionti' Review Boud: The interview included qpestions on environmcntal'to- bacco smoke expostues at home, on the jrnb„ and in social, satioQa: If case pa- .J; n. 1~.~. I l:..I l' tients ++ere too' ill to be interviewed or were dcceased; surrogate respondents (pritnarily, hutbandlt and children) were interviewed. Interviews of surrogatc rt- spondbnta were neaasary for 66.7% of thr case puiertts. Odda' ratios (ORa)' wene cilculatedl to estltnue the relative riaks. Multiple lo- aistic regression anal'ysea were per- formed using the' SAS 1,O0I'STIC pro- ccdu're (SAS Institute, Cary, N.C.). Ninety-f5ve percent contJdearr intervals (trls) were calcnlaned fian tha' logiKit: modela. The chi-square, statistic was used to taat for trend. Resulta The study papulation consisted of 210 women with histologically conftracd primary lunQ cancer who had never smoked (case patients) and 301 comm'unitybaeed eon'trol' women who had never arnok'ed! (control su'bj;cta). The buie demographic chnracterihtlcs of ttie'aae potieats and control subjects affpresehYed ilt'-I'>•bltl 1. Mhety-truf.I! percent of'the cai pasieats and 9Y% of the control subjecas were W hits. (The tmtali perantuge of' non-UVllin etindyg psnlcipan'u ref7eett the *tnil1 percent- t..•r>... 3'te (,59t:) of non-White cae pcticnrc identidiicd by hospitile and the atyLewicC cancer rcYlatty, ), Caa+o patieata tendad to be somewnat older and had fewer years of frrrtnad education than controit, with a ityniftcant trend of Increasthg IunQ cancor risk wCCth' decncasing ye'ars: o,fsetiooling ('P' .019). Aiinost'hslf of thee c'aaepa¢ientsan'd eontrot subjactr hadi Iived in Flonldi' for ><t leaw 20 yeus, Table 2' indicates the i andl 95% C7i aaeociat.d with exposurtt' to, ci'ga- rettr smoke from p'areata; sibllnQs,, hus- bandti and other household membert;; o!ltsr adjusitmant (or aP, rtce,, and education. Unexposed indi.ioduah were those with no household environmental tobacco smoke exposure. Wo describe exposure in'terme of amokrryeara, de- t9nrd as the sum of'the reported years of sxposure to' cigarette amoka from each smoker'In the household. We considered smoke-years to be a mooe reliable meu. ure of exposure than pack=yestmsi, study panldpanfr had lesa dtil5athy ,_. collina, the number of years they had ltivad'with sameone w1>o smoked than recalling the number of ciprettea per day to which thry had been exposed. Smoke-years were subdivided into throe categories of appaeximately equal size Table 1: Diimbvdon of tedecced c1w.vui of au ptt.snta and eowol wabieca Cso paciaan fn - 2:0)' tltuacaefisUc tVO: ve. Control lutijoca (o - 301)" ~. ~ tt,ei wlt:. 196 93 2St, 94 Yon i1/h it.. 14'' 7 17' 6 birth rear 9efi=% 10•20 1s7 6lS' 139 9~. 60 . t9P0.1929 1"_' 25 ' 73 24 1930 or 4rer 2'J 1t7 49 16 Wtriuitaua Mitrnrd I nd S'I 1174, <1q Otlter I I02' 49 . 127' +2~ Yean of .dueatru. a tiraa,. t>? 19 ' 37, ' 1::. Y.11 ittthq ?D. 17, so'. 17~. >'13 r.raG.N 65 ~ ?'21'. -a vcrr it Fbnda <10 l7 22 45 2-1 IU+t9 aM1 KI 89 '0 20+29 34 I n u, ~1Ui a, 11 1'1 y t,ing eutCe! w11 ry'pM Adewuxmom. 129 h' I I Sqyrtmotu.cetl carneartsa' 36 17 Sm.iluU ureirona 14 All ot.ler 1; I'3 'W~ttoe.~mc7,.d adtlllo totat beuu%c ofimiuinj; ~ C'att.: lourn~4' 1 :hn !+.uona': :,ancc: Insci:.7c

«~ 1, J^ ly 113 ' a3t'11! :r?2 0212 ;mr., [or botb earty and sdult yeira! Zlhs dtc- tribtttioa of smoke-yexr: of, exposure wsa a.tuch lower for early years, pri- ma<ffly beciufe parnicipanta tended to livo iwitli spousa for more years than thoy, kad lived with their parenu, result- ing in lower cutoff ppints. (,¢mj canctx riak eatdmura for woroen who' were eotpoaod to envlronmentail tobacico smoke during childhood and''. adolescence arro shown iin Table 2. W,ben we calculated ths risk aaWcaated with eaoposure to smoke fiorn family, matslbera on an ind'rvidlnalll basis (nsotjer, father, sibiings, and othera), tben was a siight inuease in riak for all esqpoistaac,a, although the increases in risk were tsat statlstdcally, si.guiCticaut: How• ever; Khen wo caulculued risk acrording to smake.ytoira of'expostrm which re• fdectit totsi i exposure to smoke frotn! a'll! houswehdd members, a signifrcantly' ele- vated rdsk of'2.4(9596 Cli= 11.1-5:4)was', otiaesved for women exposed 22 yean or nscne. Tabls 2 slao s,hows the effect of en- viboamlentaill tobaeco smoke exposure during ad'ulthood on lung cancer risk. B/ottsaal who, lived for 40 or more years of' thair adult' livea with huab'a'nda and ot4e'r, individuals who~ smoked were found to have an elrwatedl riak' of 2.4 (95% CI - ' 1.1>5i3). If we considered only srnoke exposure from husbands Gtr 40 or more 3Imoke-years (data not shown), th'c risk escimare decreased sliehdy to 22 (95% CI = 11.0-4,9): Ih terms of total llfetlmr: sa)oke-yearss of cxpoe'urr(Table 2); tw sigmKJant'cx- cess risks were otxcrved' for women re• portinQ fewer than 40 lifedtne srnoke- yean, but' women reportin:g 40 or more years of exposure experienced an ele- vated 14nQ',cancer risk of,2.3 (95A6 C. - L 1.-d:6), We adao examined the', relatlons'h'iai be"n the lnng, uncu risk sssocutedl with tnvironmental tobacc:o' smoke ex- powre and luttg, cancer cell type. Slncc 61.4% of the lnngcancers in the study' were adenocarcinomu, sll lung cancer histoloYies'other than adonocarcinoma were combined in one group for anal- ysis. R'isk estiinatea forcmolt,e-years of ezptssurc! were calculatedlseptrately for, the two groups, tndl the rerttlts tire shown In Table 2. For women with tdenocarcinomy, the riska were sliQhdy elevated for all ca2e- goriet of smoke ezposure, but the re- sults diAl not achiieve sltatiisticall significance. Women with non-adino- carcinom'a lUa`, canlee'rs, o'n the other ha'nd, showed significantly elievated rriska when their, euupoewe to environ6 mantal!tobsicao tmoke was o'f lonf durat tion. The OR indicated t threefold increased risk of'lung,cartccr for women who reported L or more smok'e-years of exposure fzom parents, siblinQ3, and others duringl childhood and adoles- cence (OR - 3.4; 95% CI a 1.1'-10.6)~ Similarly, women with 40 or more years rnf adulthood exposure to smoke from husbands' and' other nousehold membe'n czpcnieoccd a signifcant elovirtlnn in risk (OR' - 3 3: 95% CI = l.l-9!g) When torail lifetime crposure 10, en- viarttmanrai smoke wss ctnnsidered, the OR was 3.3 (95% Ch - 1.2-8.9) for the nigheat'expoaure ievel. For women wit}i', nnn-adenoca'rcinomt lung ctneera, there waa astitlatlkalVy' aignlfiunt tre'ndi off increasing risk associated with increas- iog smoke-ycars of exposure for ea'ch, type of e:posurc' (childhoodi, adulthood, andl lifetinu): Since surtogate ruspondents were rc- quired for about two thtrds of the caae pauient interviews, we iinvestig!.ted whether, the source of'the: caae patlent imtervJew' (self-responderit versus surco• Qate respondent) affected', the risk estl- m'ates. Surrogate reypondbnts for es.tar patients were dividedi into two groupa, "'husbandu" and "other surnogales," the l'ataer, group coruistihQ primuily of sons znd, daughters. The resulta of thic analyeie' are shown in Trblb 3. Becauae the numberof respondbnus, in some-catn- g4ries was very small, analyois of risk sleeoeiated with exposure to smoke from inidividuaJ houaichold mem~be'rs is Iimited'to'fr<ehen and'husb'ands. In eo'm. pani3on with ohc risk csitirn'autcs for women w'hoso natetv'iews were com- pleted by thems'clive:+ or by their h'us- b'autds• tne risk estl'mates for women in (he "oth'er surrogate" respondent cate- yory were considerably lower. This re- .ult wes true both for risk as'ociyted Tui .l~Grr.et of'.nviiomatnl :oeaoeo fmoke oe 1Wt~:ueCOr~tirk o'!'no.avnokin~t, Mi*+cn: .pAn)!rn), to itwrnx~ ull~.i.pc A'11 Ibnt canatti Adc-)ocircin.~an AlUouxr cdl trf.yn :.ipallra hlhOny ()R" 95% CJ P for, tren9! OR"' 95 -1 fi P for ircnu OIR• i!14 ,^t I for t+end Bipetew: ye ueo NaCYat 1.6, G.eF4' 1 i : 5 0.'-4 'd I 7 0.3 •d.: Puhrr L 2' C.eF2:3: . 0...2'4 I a U'-~ 7 SKitihgs and otrien 1.7 C.b1S:Y 3 0.6•2 % Hutb+ndk 1 6 QBiS~u '..3 0 A-:7 Z: 0'g<8 S melie-}tct rti C7,ildtiood%adbla,xace' (p..crx, atd i fUblinp). <'ta 0 1=3A 8 .laL 18;i'1 , I C:}.1-6~ :~.1~~ 0:4.3,U. >3B 2.a I.I-7.4 :i4 ..9 :yl 4 Adirkt^ood ;Muab.not eno otri.rs). <22'. ! A' T' 0 in-i. 7 . c I2-JY :,a I 0 5.1 <. _0 y40 1.4 '. L I.S,t 02! 8 0,7.4 +:U !3 ;)0 R A'll lifaumt househ'old',-ro,un <22 1'.~. G:e-V .. Q:°2.7 I 2 ; 4.~1'a 27.?p I'.i 0.7.1.9' :.:~ O ('-2 " 3.40 2:.1 1.1-41u~ 110i . . 0 M-3~9~~ 001 '00l sd)ua,c8 fur'.es• tliu. av¢) od.u,ion(at rM.>t:rredal8 ubll $4• Y0 '.5• Seotnmber Ir'. 1992 3EPnRTS I;tqv,

J-! :a 14 jT301 4;t2 cD2'12 ' JtilCl i'I C i r T&bk J. C6t.cr!d ca.uvsn.nul tabaoeo rrol;s oa tiay o.ooar riet< oi rxmoti wamw. raoerdtry ro 11 e(! cau pakot lnrervtev Sa.rcm ot a..w pnh+r tarsrvxw Selr (h - 70) Hucha.6 (a •48) Octter wrnopta(a - 91) 341f aad 4ea,.od (n - 1'IIEp Ps~.po..xt htstory~i OR' 95% Cl OR" 95% C1i OR• 93% 01 OO R" 95% Cl, es'9o1\R: )ItWrIQ'. Cir.tKt 1.2 a9 aI] 210' 04.&s 0.6 o:3-i 3 2.7 1.0-r:3' Mtnexnd 1.1 0.9-10:6 3a 0.7-13.7 0.9 0.4-1.9 3,t l,2-a.3. !lb'linp utd otJ,K1 - - - - 4.3 :'.3'-14 :. 3rtmtit•y.us ChilHbondladntirsaa+abt (parcntr and nblinp) c181 4.3 1.1-16.7 2:A 0.4-(2.a' 0.6' 01.1.9 3;6 V.1-IOa 1t•2r 2,l 0.5:10:6 16 0'.2-.10S 0.6 02-2.0 2.'1 0.6.7,2 a22 6 1 1.7-293 1.4 0:2-9.6 1.6: 03-4.a 414 1.4'-13'! P frrt tr.nJ .7Y 6e 07 .tdulNfootl (Itueane and' atn.n) <T3' 3.4 0.9•t2.2 3.1 0:7-14.4' 0.1 03.20 3:3 1.2-9.2: 22-39 3.6' 1.0-1 3.: 1.8 0<4-9.: 0.e 0'3• 1.9 2.'9 1.03.2 >• 40 . 4.7 1.249:1 4.2 0;1P:19 13 04-3.9 4.7 1.5.14:T P for ttand .03 .03 .3J .0tH1, AII lifatmwho.aain[d txoowrs <23', 2.0 0-S•7:6 31 0:7-i4.9 0.6 0}.1.6 2S 0.9 -1:2' 21.39 4.4'. 1.3•(5.6' 1.0 0:b:.6 0.6 01•1.4 3.1 )! 1-a.6 ,V 40. 4.1 G t.14.a 33 0:7.16:7 13 '. 0:7-3.6 4.0 R14.11.3 P fn trxnd .01 .15' .r:1 .004 'otL d/tutM for ep, rramt, arrd e0vcatfbe (![/ aad >a'ert,dea). with axposure to smoke from individual houeaho'f d! memiaen and for riek ~ asaoci- ated with bousehold' smoke-years off exposure. Given thar' the rink ctufrrlatea for xlf- res'pondents, and spouse rt•apondenrts were so similar, we repeated' the ana1L ysie, exclud'ing "other sunro,gete" re- sipondeniu. As shown in rabile 3', li'mitinQ the case patiienth to self- respondeats and apouse respondents,rc- sulted in sfgnllaasntly elevated rlshs u+ sociaredwith cxpccxure during childhood and adolescence to smoke from siblings and o'thers (O:R - 4.3; 95% CIi - _.3-14.2) and with exposure dltring idulthpodlto,snsoke:ftomi hustsands (0'R' = 3.); 95% C1 • L1,8.3). When smoke- ye'ars of,exposure were conaidered, rta- tdctica(Iiy signifiunt increases in, risk we'ral seen for thr lowe.tt and highest cetegories of srnoke-years of exposure to smoke from pareats and sibl'ings;,;h'e r~isk cstimate for tfic highest cxposure category was elevated to 4.4 (959o CL= Wficn! amoke-ycata oi adult- hood cz'posure to smoke from husbands and othets were considered, stntialicaDly significant alevatibtrr in risk werc: seen for the lowest and highest exposure cat- :goraca and borde:line significance was found fon che interrnediatt, categor y. For the Cigheat, cxparewe category, the risk cstlmauc, inaeu'cd :to 4:7 (!959'0: Cl m l 5-14.7)., When Iitatime' hoaulxaldl ex'- posure wu coruidlered, a cleat dose- reaponae' effect' was avident: Risk estsi tnatea ,increaacd ~from! 2S' for fewer than 22' emoke-years of e:piowrt: to 4.0 for 40!or more yeara of exposure. 'i?te t;am• plc beurae sm'alll when we considered differences between lung, cancer cell types for thc different respondls'nn groups; nererthelieta, higher estimates wercstill assochttrad with women diag• nosed with non-adenocarcinorna lung eancers, con'aistent' wdth the analysis from the full dauseta We found no sottltdcally slgrtl6cultt increase in riitk associated with cx- posure to environmental ttabzcco smoke at' work or durnng soeia[ tctiviti'e's (det: aot thown):. DI§Cllttston The reeulis of our atudy nd c.te thyt the risk of lung cancer i',s incraased among women who aro the:nselves life- timc nonsmokcra'but who live ir. iottse- hnids with smakers. 131eratec r:tks were seen most coneiiltentlywhe,7 expocuresto, housi imo'ke: occa'rred during adulthood. Womi with aom-adeno- carcinoma lun'g cancersi wr,o n:poritcd high levels of exposure to housakolc' smoke had the rnmt pronounc.cd clcva- rian in -isk. 'Phere was sug,y;stive evi- dence that prolonged expoyure tic tobacco smoke during childhood and adolescence might also be assaeiate'n with an increased risk of: lutig cancer M association between exposure to envirorlmerllal tobacco smoke and the development of nnn-adenocarcinoma lung ancens has heen noted in severa: other investigations, both in, tae Unitied Statea and abroad. In a audy thatpooli:d data frmm, three case-eontroll studios, in the United' States. Da'lagor, et al. (9) re+ }i ported, an a'lmost threefold increased i :isk of sqpa'nous ccl!I ana small-cclP lung carcinomas aimanig madr r,r.a j ft:rnale' lifetime mmnsmokars who were I marriKe to smokers, but, they observeo no in'crasaet: risk of adtaoearcintnmas: Garflnkel er, 21. (,110)' investdgated the distribution of varrous lung cancer I lologtes arnong iifiernme nontmokingg women :n. New Jersey and Ohio. They `ound r,s.a womtim whn.c iuisi sni had i fi'srofold, increase in rilci ol' squanou6 cedll lung carc:isomas, bu: no stasirticaliy si,ghificaat increa'ae ta risk of cther::Npc. of luna cancer,. In a study conducted in Louisiana. Correa ec : al. (6) reporied r doubling of '.ung can- ~' cer risk among nonsmokers marricd :o { smokers, bocd' meilc and femalc. I \hhou>zh the risk etti'matrs were ricr i xeseated ac:ordiag to hiatm'logic dasst- `iea1tio'n of the iung cancr.rs. :no auti,crs 1420, Jwr-ial .;i rr.c VatiooanGnce: InrtnLtr

. I Ej9~' 1'Si^:: 15 : 15 -a301 402 0212 JNC I i I C I C indicaucd that't''he ezeiusion of adenocar- cinoasa from their analysis prodtsced a etrti.ticaly significant linear trend' of incre'asing risk with increasing ex- posure: In noi inNestiiiation of non-edano- carcinoma lung caaxrs in nonsmoking Athenian womeo, Trichopoulor et al: (11) reported a risk estimata of'2.M1 (or women whose huabaruls smoked fewer' than 21 cigarettes per day and a risk astlmate of 3A for women whose hus- bands srnoked more than 20 cigarettes p6u dYy. An association betiwet:n mar: riyge to a smoket utd'an increased risk of' sntal'f-ccll and squamous eeU lung carcinomu was also observed in a study of Swedish women (77~ For other lttng, cancer cell types in the Swedish etudye the rialrs were clow to unity except in the eaus of women with high expoanre levels, whose risk was doubled. A study of lifetime nonsmokingwomcn, in Hong Kong by Koo et al: (1J) showcd that etr- poetuc to environmental tobacco smoke was associatnd with i an clcvatcd I risk of spuamous cell and large-cell car- cinornas. These nexultt conflict with tihote obscrYed inia mufticentered study in the United Stetes (f), where an e9o- vated risk of lung cancer attrfbutable to paaalve smoking was limited to patientss wtth adenocarcinoma; these Indtvid:.rals experiencedl sn almost 50% increase in risk. In another aludiy conducted in Hon& Kong, Lam eral. (14)~ reported that' lifetime nbnsmoking, women with }iusbands who smoked had an inericased risk for the develo;pcrent of', small-crll caroinomala.adbnocarcinomar, and, large-cell carcinomas, but not s9ytaaaotrs ceil carcinomas. Our, analynis of [he cffcct' oc cigir'ettc smoke exposure during childhood andl adolcscence on lung cancer risk rc- vealed an incrwaacdk risk in women with -2' or more total smokc-yeanm of ex- posunc. This excesx rlsk for'the hlgbtntit exposure category •.vta statiitically sig- r,tflcant fdr al] lung cancers combined and for non-adenocarctnoma lung can• cers. A po!sitirre assoclatlon betwe<ni lung cancer risk and high levelr of en- vironmenral~smoke exposure st i ynunY age haa also bcen reported by :anench er al. (5), and an increa!sed oversll can. cer risk among indtvidlr.lt exposed'•ro crQkrette srnoJe ue childhood' hrs been aobd by Sandler at aL (7). tu studits conducsed' by Correa el a1. (6) and Wut et al. (8), the inc7euxd lung cancer risk newlting frons childhood exposura was four>,d to be suoci.te.d specfflcsVly' with matcrnal smo)rlhg, wherosa'iniour atudy wpobaerved Ibai variationln.. rirkar cording to which family memben smoked. In thc interpretation of the results ofl thle study, one area of particular con-' cermi ls the lmpact of r2spondent1 type on the risk estimates, Although the risk estimates based, on responses by the cst:e patient and her husband are reason, ably similar„ given the sample size, the risk estimates bsend on "txmer, surro- gate" respondents' (primarily'sona' and daughters) arn considerably lower. One poesible explaastioo is that t3se children of the case patients selectively under- estimated the ertposures that their mothers received, pa'rticularly' fiorn theiu fathers' cijsrette smoke. Convcrsely, the case patiente and their husbands may have overatimar'ed' the exposurr. Few studies hare presentedl risk esti• matea rer:ording, to respondent typc: I><oorich et al. (J)' obtcurved that lnter- v4ews with surrogate respondents pro- duc'ad ltnwer passive smoking risikk estimates than direct, interviewt. Data on variLtions within the surrogste:yroup were not' availsbla: In tnother sttrdy on pastive smoking, Garfinkel' et al. (TO) reported that the highest lung cancer, risk estimates were bued on responses by the children of', tha study subjects, a finding opposite to thrt reported 4ere. Another issue tbat must be considered in the evaluation of our Sadings is the possibility of' miacLaraifikati'on of' smokers as nonsmokers. Although cvcryy attempt wss made to verify that the case patients were truly lifetime nonsmokers, only orel reporns ol'smwking status wcrc availkbic. Fontham et al. (4) ascorta'ined' urinary cotlnine levels to confiimt self. rtportl of smoking stsrue~: The results of this validation procedure suggested rhat, depending on the urnnany rAtinlne Irvel selected to indicate active smoking, either rD +ttJF,' or 2:49t, of ctae patients and 2% or 3.9% of' population control sub- ]cctb enuld have been miitclassiried as lifetime nonsmokers. If ohese same per. centages.re applied to our study, rnen ^wo to five case patients and six to 12 eoatrol subjeas may have besn inc.sr nesly clsssifled se rtonamokers: In aay ualysit that distinguisbcs br (wean lung, cancer c.ll types, tbeI arcuracy of the hisadogical clasaiflcaaoe must be considered. In the present study, wbich included' many hoapit&la throughout central F7orfdh. an indepettd- ent pathological revdew' was not poui- ble. However, the dlistriliution of' lung cancer'cell types ln our'study was simi- lar to that descrlbed by Fonthttat et aL (4)l who did conduct an independtnt pathologi+cal review. In the tattar sardy,, the pathoUo;gieal review, rresulted in re-' classiflcatlon of' approximately 25% of' sq}uenous cell carcinomas and' 3916 of lotrgo-cell carcinomas aa adenaear- cintmmas. Of turtton originally claasifded as adeaocarciawmae, 97% were cor- realy classified according to the inde- pendent' reviewers. By eatrapolation,, any, miselassifications inw our owsn 3tudy would tend to nsducx the diiKercaces it risk estimates between various luttg cano eer cell types, since the ex'ceas risks were zssociated primarily with non- adenocarcinomas: In coneluslon, the results dest;ribed here suggest thaYJong-term ezposune to cnvironmenta4 tobacco smoke itttzeasea the risk of lung canncr in women who are nonsmokers. Ili!tks' appeared' masr elevated for, nort-adrnocancinoma 1ing cancers. High levels of exposure during youth and adulthood may each, play a role in incrersing lung cancer risk. EReftrrtmces C!'YSvKo\oN GeNiRwl., Dkr.a'T1nlhr071'tnALTFI,I ta71:C..TfO.A. ..l.'J wiYLYAaa: T}11 HeirtnConlealrancts' Cf Iavutunury' SraoVt-i'nr: A Report af't1e Surdean G'encrni DkEW Publ Ho. (iCDC,)87•i,398. w'rth- ingon. D'C: US Cvvt Print Off.' 29P6 (21 nrlAln.rlMi[V41/lrlYt:/r.:n1'.\t. STVolts .~NOToKIICY)Lr/~nY. CnM-lirat nnA1.f3r1t,. SMOKING. tivTtnn•.L Rr.vwe0x Cotlr+c7LL `.rnnw.r! Af.rw.qr,rjF SIIIlMCEr: En~tron- rnental TObecco. SmnkeWescurint (;- po.unr and Na+.ce'tarrg, Heelth BttKCa R'.ahinatnn. Dr.': Nal %ead Pmt, lYb'e. 1VArbqr.nL lN%ti-tt:TF. .rnK OCCi:PAntQ,r,L i.:Gvvan Hrar rr. D'1rAKrMlhT. n- Hawt_nt +un:Hl^rnS Siaantfxs: VIi05~+ Cumem intaurlienee Bui!.rin 34: finvdron rcnul T1'oeaern Trncka' in the Workoicc:. Lune Canccr ana. G,th'.r H.clth 6HnaaDHHS Puet :+b: (Y10SH)91-10e wern. tnywn, tDC: ;;5I(w,.t Prfnt O/r. 199Ii. ;~(1 ForYTNnM ET. ,nler. P; wt).WIL'1,y>`~a A. GT .r.: Lunt,cenecr ,e nonsmokie;t+••otncn Vol. flA; No. Ig,,Septernoer 16. 1992 3z?pRT"S 14:

. ~ . J Vk1V 1-IW`Jl !to= 1'/ .• j 1422 Arnultluatlt,ea.zraontrol amdy. Canou l~IdemloL alole'ankarn dc rzsy t:93-e1, (3) lNr.eaiert DT. Tltowti WD. Wruttt,A Lt4 mr..u t:ain{ wscrr ,od!aspown to cotiueao amoka Ia Hfa kouarbold. N Uel 1 Med 72lf6Dt*63d, 199t1 (!S) Cbnaal. f. Plaaa'1w, Foxrw.ar,E er a't: Pai.lve smottnt and lana aacer: L.ncct 2:393-547, 19e31 (7), Swrrot.ut' DP. wn.cox AJ. I:vuaou i R8. CwaaitW.e etbw ollll.tfmm psulvt nttak- Ua on oaoo.r ritk. tsaost 1:312-] ta, 19C? (Q), Wu AH; Hnrawoh,nB. lhtta MC, .* -L: Srno=at,u+/ otkr'rutrfa0tort (or lune',oan'g ar in woar+. 24Q 7Ac7x7-781. 1985 . (0) DaAOaa N+a, the;ctr'LW. MASoK TJ. ar . AL: n; i.laaoa of pr.aivs amoli to lang ca.or. CJaeari dd-d90"c1. 19Mi (10) 1 Grtuwceat,l, AuaaaAcrl O.Jausanrtc,ht• velwnry.aokln8.ad tea6 caewr. A eada. ooaroi Iaatdf. INCt' 75:e65.-f69. 1M (1J)',liuctanotfuw tA 1Wwwota i t, SpAstat>t' G ar A't: litans aaorer'aud'Mattva .noklet;; G'+t l Qaeotr 7J:1-t, l0Y l (12)' 1'eaaxA'aAH 0. Naus.r L SwutasoN C: rtrai re staokin6,and Itaj ana.rie Swdlah wao.e. AM 1 EpideiNol 12]:'17 -24: 1987 (Jl!) Koo LC. So JIt, Sww'D. er .4 Msansa nwats of pa/aire amokina and utiinahea of lua6 eaaotr tuta anm.6,aaremotJtt6 C7ti- aoa famalae la J Catta+ 39-161-169, 1967 (14)' LAtd T}I, Ytmo IT: Wmw CM, ar A'u Smotdaa,' pu.ive tmokiit{ and lifudbliaal typw in Iuaa oanoer Ia Hoea',1Goee,Cbtena aro.na.. Br l'CJaatt $617S-67YJ,19A7 Canii ihi Ptat'lrnts With r*malc Lymph+ocytic LeukeDai a Lois B. Travis, *' JlwpheJlre F,. CurtiS, Benjarrurt F. Joseph F. Frcumrrtl, Jr. ~ i Biack,y,roun+d: Reports to d' k have' proNidsid' widely dHrergea estltnata of the risk of'socoad m=aaat neo- plaams In patients witlt/chroaic lym, ptioeytlc lsukemia (ic.I1:L); rattging from canrar daficilj,( to' excesses of' tw.fold to threelrJld. Purpos.: Our parvoat was to etatltnate the risk of second pritaa cancers followlitQ CLL, utlllsi.6P oputat'lon-baaed tu• tnor ragirRrile, aad to determitte whether site74pedflc excesteai m'd8hf be assoetli with type of ini'tlat treatiaeat for CL1;;. Jllret6ods: We Q30'1i 402 0212 JNCI/ICIC rnal'JaKd data for 9456 partleats dl,<g'etoaad with CLL aa a firrt pri- mary canrsr between 197]' aad 198d, wtw , wars reportod to .au of dae tu- mor regit+triee p'articipatlatj In t!he Matloaall Cancer Iuttl!tttte's S'ur- relllaete, Epid.mlolegyy and Endl Resalta (SEER) Praqr>tm' and who, aurvlli 2 or more moatbl. SEER portaant'to ielarify the nctra ito CLI. patients potential impaet on pa- enl. follow-up, and sur- even vario'us repona to date A d diNergent estimetra of'the aeo of second malig,nancica in patiertts, ranging' from cancer de5- flles were aareftud for ta.asi*ne pri- cit, to excesscs of, tiwofdld'to threefold mary nmliigntta!ciet that devdaped' at (11-2t1): To futtlter, explore'and quantify leaat 2 montfst after the lbitial (TLL j4he risk of second cincer& amomg a diaptosll. Rarlr:: Cbmparud with the,i large number of CLLL patlente in the general population and to examine uso~- ciation, of ' risk wtth initial therapy, we conducted a.turvey of mote tltalt 9000 such aubjecu reported to thoi National Cancer Institute's Surveillance. Epi- demioliagy, and End Results (SE?E'R')' Program t from 1973 tbrougb 1988. Slince CLL patients ara frequently, treated only with alkyUuing agents with- out the confounding effeew of rad'io- tiiarapy, thia graup' of padenu iprovidw a spocial' opportunity to study the. late suq,uelbe of'these drugs. genrral populat'lots, CLL ptttlieaye datttvaatrated a lal`aificanrtl Kty creaoed risk of d"drtlpimig all' a.eoad aaoartt (8+f4 oburrei eboermdd-to- e:pacted ratio (n ' a 1.2R('9'y96 ao.- 6dcace iatcr.al' (Cl],  1 A1!9=Y.37). Sig: aiflleaot e:crsaaa werre cancern of the lung, ( brain (p/8 a 1.95), aa lar mdanoms) (OJ19'i malLgaaat molatto and Iiodgtdn''s d Cancer rltlt, eordllii to Inl was also cc tarvalt after :icn: , CL.IL cantly eNnond tera o. e veto nan be im ot otcd for E  1.91)r, ye'' (dntraocu- .9'I') ae well as (IO/E a 2.79) (OfS'  7.69). dld a.t .ary' ae- tlKatme>Ot catlgqry, at nt:raw atl tttne In+ dlapwir. Couc4ri tDents ara' at a aij(ntf3+ ritk'of'dtrvelopMg a ant aeopiaam: Tbe pat- caacer ezceates tugyettb a ty etata patalWag the de- eat of selected' eacoad mailp t l)tpadmta with CLL, perhaps of abared ettol+Kik factors, nologir Impalrmen't, and/or In (tuenoes. .Ut6eugt lour resulta not auggest a ttt^oag treatment eftect, more detitll.d studles of'second tumors In CLL are tt.e,ededo to investJ- pte t6r rok of 'nadlatlon 1 therapy and motherapy. (,J tlrtl Cancer liatt 1427, 19921'I Patients with chro Icukemia (CLL)iexhibit a v munoloQic penuztiationi (1-4): tha increase their' risk for' eeennd malignant ncopiaems: The occurrence of frmiliad CLL may' alto suQgeet, for some sub. jects, genedc detera'tiitan'ta (3-7); such ar: thosa that underlie other aats of'mut: tipie primary cancers (8;9)j Morenver, radiotherapy and' ehemath'erapcutbc agenta may also contribule to subsc- o,ue,at mallgnaneiai among canrer sur- vivor. (1t7). It it nislc of'second becausa of t tienc muta vivaL II[ have p occu a 007 Patlents and Methods Wk analyr.ed all patients dlageosed with, CLL aa a first .primary cuncer, be. tween 1973 and 1988 who were reported to one' of nine poputatioa-basedi cancez rsgktrias of the SEER Prograat i and cur- viwed 2 or more i months. Sacb rsgietrias inchude thoyt irt'the metropotktn arieas of Recelved Januuy Itl, 1492: nevised May Ia,. 11992:' aeeepred i Ju nc,.. I ID7t. L 8. Travis. Q. E. Cartls; J. P. Prtvmcnl, 1r' (Epidbaliolo6Y .ad' 9io.taliatiG Ptorrant; DiNi- non or Cancer Ettob{y:, 8. F. 1(ankey fQloer Statlalto praecn, SurveJlr:ioa Pnetrlee. Di-ioton of Canco: Prcvcntion and Control). NtuOn'il Can• cor'Ini Bakusda, Md: We aro indcbbed to tha State Hnlth Relirtry nf lnwa (MM. Ralhleur 1/t)(car and I Dr. 0ari.a F Lynch) for dtta.retrieval. :n Dn. John tloice: heil C.aporau.and Mantu,L3rsl :ur critint rc.AcW of :he mana.cnp,l..and t.. Ma. SaedyCoopartiR+irA tn0 Mt. S'ntncy ('arkia for aocrouriai sttnpon. 'Co.+e3ponAlner rtx•. I:o.it.B. Travic:.titLD ~. E:- ire etiza North. Sae. Wd, NattoAUlInstlWttv of H~Rahcwa- MD b1a97.. 1114. nota. The ttrontun Is a set of atOtraph- .cany d6ilaod t+opllltonn-0l«sd c.ntrd tumor, re5. +triq inlh/; Untttdi Statt3,. optrlttdl by local nonptOGl ottudtauoeu uadtr'ootYna to th. Na- twnal Caatsr Institntc (I:CID: Faa6 retiatry an- naatlv fvbn~iU itu casca to -ia MCI on a computa uP.: 7liesa eompuur tapn rt lh.n edliW by ih. `K7' and mtde arailtbit fuc analwn(t. Juurnal of the 4aiional Canev 1¢strtctc