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Lung Cancer in Nonsmoking Women

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					                                                                                                                                                   RW LP0034

                      Environmental Tobacco Smoke and
                      Lung Cancer in Nonsmoking Women
                      A Multicenter Study
                      Elizabeth T. H . Fontham, DrPH ; Pelayo Correa, MD ; Peggy Reynolds, PhD ; Anna Wu-Williams, PhD ;
                      Patricia A . Suffler, PhD ; Raymond S . Greenberg, MD, PhD ; Vivian W . Chen, PhD; Toni Alterman, PhD ;
                      Peggy Boyd, PhD; Donald F. Austin, MD; Jonathan Lift, PhD


                         ObjectWe--To determine the relative risk (RR) of lung cancer in lifetime never                             to the US summary relative risk (RR)
                      smokers associated with environmental tobacco smoke (ETS) exposure .                                          estimates for lung cancer. 1 .19 (959a con-
                                                                                                                                    Sdence interval [CI], 1 .04 to 1 .35) associ-
                         Dasign.--iLAulticenter population-based case-control study.                                                ated with "ever exposed" to spousal ETS
                         Settlng .-Five metropolitan areas in the United States: Atlanta, Ga, Houston,                              and 1.38 (95% CI, 1 .13 to 1.70) for the
                      Tex, Los Angeles, .Cafrf, New Ofleans, La, and the San Francisco Bay Area, Calif .                            highest level of spousal ETS exposure .
                         Patients or Other PartlcipantatFemale lifetime never smokers : 653 cases                                   The weight accorded this study in the
                      with histologicallye/,lnffmled lung cancerand 1253controls selected by randomdigit                            EPA report reflected the large number of
                      dialfng and random sampling from the Health Care Financing Administration files                               lifetime nonsmokers with lung cancer
                      for women aged 85 years and older .                                                                           (n=420), as well as the study design used
                         Main OufeomsMeasure : The RR of lung cancer, estimated by adjusted odds                                    in this case-control study. This study was
                      ratio (OR) with 95% confidence interval (CI), associated with ETS exposure .                                  designed specifrcally to evaluate the role
                          Results--Tobacco use by spouse(s) was associated with a 30% excess risk of                                of ETS exposure in the etiology of lung
                       lung cancer, all types of primary lung carcinoma (adjusted OR=1 .29; F< .05), pul-                           cancer in lifetime nonsmokers .
                                                                                                                                        Two large US studies have been pub-
                       monary adenocarcinoma (adjusted OR=1 .28 ; F< .05), and other primary carcino-                               lished since the preparation of the EPA
                       mas of the lung (adjusted OR=1 .37; P=.18) . An Increasing RR of lung cancer was                              reportS~Because theae studies are simi-
                       observed with in(xeasing pack-years of spousal ETS exposure (trend Fs .03), such                              lar in size and scope to our first report,
                       that an 80%excess risk (it lung cancer was observed for subjects with BO or more                              their findings would have had a similar
                       pack-years of exposure from a spouse (adjusted OR=1 .79; 95% C1=D .99 to 3.25) .                              impact on the summary US risk esti-
                       The excess risk of lung cancer among women ever exposed to ETS during adult                                   mates. Brownson et ale observed no in-
                       IHe in the household was 24%; in the workplace, 39°/a; and in social settings, 50% .                          (xeased riskinthe ever-expoaed category
                       When these sources were considered jointly, an increasing risk of lung cancer with                            for spousal ETS (adjusted odds ratio
                       increasing,duration of exposure was observed (trend F6 .001) . At the highest level                           [OR]=1A; 95% CI, 0 .8 to 1 .2); howeve
                                                                                                                                                          .19, the US summary    ;theCIincluds1
                       of exposure, there was a 75% Increased risk . No significant association was found
                       between exposure durirlgchildhood to household ETS exposure from mother, fa-                                  point estimate. The highest expo sure cat-
                                                                                                                                     egory(greater than40 pack-years) in the
                       ther, or other household members; twwever, women who were exposed during                                       study by Brownson et al yielded an RR
                       childhood had higher RRs associated with adua-lile ETS exposures than women                                    estimate of 1 .3 (95% CI,1 .0 to 1 .7), quite
                       with no childhood exposure . At the highest level of adult smoke-years of exposure,                            similar to the US'7tigh-exposure" sum-
                       the ORs forwomen with and without childhood exposures were 3 .25 (95%Cl, 2.42                                  mary estimate of 1.38. In the second study
                       to 7 .46) and 1 .77 (95% Cl, 0 .98 to 3.19), respectively                                                      by Stockwell et al9e the RR estimates
                                       .-Exposure to ETS during adult life increases risk of lung cancer in
                                                                                 .Conclus                                             are among the highest reported for US
                        lifetime nonsmokers.                                                                                          studies : 1 .6 (95% CI, 0.8 to 3.0) for ever
                                                                                                      (JAMA. 1994;271 :1752-1769)     exposed and 2.4 (95%CI,1 .1 to 8.3) for 40
                                                                                                                                      or more smoke-years in adulthood .
                                                                                                                                         This report extends the 5ndings of
                                                                                                                                      this multicenter study on completion of
                                                                                    IN JANUARY 1993, the US Environ-
                         From the Deprrment of Pea,ology (Dis Fornthem .
                                                                                    mental Protection Agency (EPA) issued             2 additional years of subject accrual .
                       Conea, and Chen) . Louisisna StateUniverslly Medical
                       Center . New Orleans: the California DeParlment of           a report on the respiratory health effects
                       Health Serrices . EmeM!ille (Drs aeyncles and Austin) ;      of passive smoking in which it concluded          METHODS
                       the Unlvereity ot Soulharn CalHamle Schoct of MoCb
                       cine, Los Angsles (Dr Wu-Wllleme) ; the Universiry of
                                                                                    that environmental tobacco smoke (ETS)               The methods and procedurza followed
                       Texa6 HeaM Science Cenler, School 01 PYbllo Heallh .         is a human lung careinogen, responsible           in this study have been previously de-
                       Houston (Dre eualeranC Alterm2n) : the f :mmy Univar-        for approximately 30001ung cancer deaths          ecnbel in detall? The study was a popu-
                       aiN School of Public Health, Allanla, Ga (Ors Green-
                       b¢rg end LNtg antl the California PubFc Health Foun-
                                                                                    peryearin US nonsmokers.' A total of 30           lation-based ease-contrulstudyoflungcan-
                       dattion, Emeryvllle (Dr Boyd) . Or Bufller is nav with the   epidemiologic studies conducted world-            cer in women who have never used any
                       University of Californle-BSrkeley, School ot Public           wide were included in the EPA risk as-           tobacco product . Eligjble cases included
                       HeaIM . DrAllerman Isnowwlththe National Institute fcr
                       Occupatlonal Safery end I1eaNh . Cincinnati. Ohlo.
                                                                                     sesament, including 11 etudies conducted         microscopically confirmed primary carci-
                       Dr Austin is now with the Oregon Health Divislon,             in the United States .'s91 Of the US stud-       noma of the lung (International Ciassi-
                       Pertland .                                                    ies, the report of findings from the first 3     fication of Dfseases, Ninth Renisimc [ICD-
                         Reprint requestato Louisiane SYate Univurairy Medl-
                       caI Center. Department of PathotogY .19111 Perdldo St,        years of this multicenter study2 contrib-         9],code 162) that werediagnosedbetween
                       New Orleans, LA 70112-139a (nr Fonthem) .                     utedthegreatestindividualstudyweight              December 1,1986, and November 30,1988,

                       1752 JAMA, June 8, 1994-Vol 271, rJo. 22                                                                     Tobacco Smoke and Lung Cencer-Fonlham et al




                                                                                                                                                              PM3006584828
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                      among female residents of inetrropolitan Ofthe17447potentialrasesascertained itythatthestudyfmdingswerebiasedas
                      Atlanta,Ga(Clayton,Cobb,Del{a1b,Ftd- inthefiveetudycenters,800werefound aresultofinclusionofetudysubjectswith
                      ton, and Gwiunett counties), and Hous- to meet all eligibility criteria In-person borderline concentrations (65 to 99 ng/
                      ton, Tex (Galveston and Harris counties), interviews were completed for 665 (&3%) mg) of cotinine(creatinine .
                      and during 2 additional years, 1989 and of 800 incident cases and 1278 (70%) of Representative diagnostic specimen
                       1990, among residents of New Orleans, 1826 population controls . An interview slides for each case were requested from
                      La (Jefferson, Orleans, and StBemard was solicited from the next of kin of cases thehospitalforreviewbyonepathologiet
                      parishes), Los Angeles, Calif (Los Ange- who were deceased or were too ill to par- specializing in pulmonary pathology . A
                       lea Count,y), and the San Fcanaseo Bay ticipate in an interview . Information for total of 5GL (85%) of 663 potential cases ;
                       Area, Ca1sf (Alameda, Contra Costa, 2411ung caneer eases(36%) was obtained had diagnostic material available for re-
                       Ivlarin, San Francisco, San Mateo, and fromnextof-kinrespondentsm view,and562(98%)ofthereviewedcases
                       Santa Clara owmties) . Additional eliq'bfl- At interview, a urine sample was col- were confirmed as primarybronchogenic
                       itycriteriaincludedageatdlagnosiis(2g lectedfiomallconsentingstudysubjects carcinoma . Afterexclusion of the 10 cases
                       to 79 years), language (English, Spanish, who were able to provide such a sample . that had review diagnoses inconsistent
                       or Ch'nrese), history of previous cancer Urinaryeotinineandcreatininewerede- withprimarybronchogenicrareinoma,the
                       (none), and lifetime tobacco use (fewer termined and the ratio used as an indi- fmal interviewed case seriesincluded 653
                       than 100 cigarettes smoked and no use of eator of current smoking status . The re- lung cancer cases: 497 adenommanomas
                       any other form of tobacco for more than quest for the sample was not made until (76 .1%); 74 large-cell earcinomaa (11.3%) ;
                       6 months) .'1'6is projeet was approved by the interview . Specimens were stored at 40 squamous cell mrcinomas (6.1%); 24
                       aIlappropriateinstitutionalreviewboards . -20°C until analysis at the American small-cellcarcinomas(3 .7%) ;andlSother
                           A population-based control group was Health Foundation, Valhalla, NY . primary lungcarcinomas (2.8%). The 101
                       selected by random digit dialing and Cotininewasquantitatedbyradioim- easeswithdiagnosticslidesthatwereun-
                       supplemented by random sampling fromn munoassay using the method of Haley et available for review were classified ac-
                       the Health Care Financing Admhdatsa- al86withamodificationoftheantibodyof cordingtotheoriginalhospitalandtumor
                       tion 51es for women 65 years and older . Langone et al's Cotinine concentrations registry diagnosis . The distribution by
                        Controlawerefrequencymatchedtueases were adjusted for urine flow based on celltypewassimilnrforthereviewedand
                        on race and age (younger than 60 yeals, creatinine values by determining the nonreviewed cases except for a higher
                        60 to fi9 years, 60 to 69 years, and 70 to 79 nanograms of eotinine per milligrams of proportion of eases in the "other primary
                        years) In a 2:1 ratio of controls to cases creatinine .Crestininewasdeterminedby lung carcinomas" category among non-
                        and met the same residence, language, spectrophotometryt>sing'theKodakEk- reviewedcnses .AnalysesofETS-related
                        azultobaconuseeriteriaascaeea .Thepopu- tachem400C1miealChemistryAnalyzer risk estimates were also conducted ex-
                        lation control group was selected as the (Itodak, Rochester, NY) . eluding ceses that did not undergo inde-
                        primary comparison group in caseeon- Urme samples were analyved for 356 pendent review to evaluate consistency
                        trol analyses. A second control groupwas (63b%) of 665 cases and 1064 (83 .8%) of of the findings .
                        selected during the first 3 yeare of the 1278 controls . The ditfference in the pro- In-person interviews followed an ex-
                        study (December 1, 1985, to November portions of cases and controls is attrib- tensivestructuredqueationnairedesigned
                        30,1989) from women aged 20to 79 years utable to deceased cases . A high propor- to obtain information on household, oc-
                        with a diagnosis of primary carcinoma of tion of living study subjects were able cupational, and other exposures to ETB
                        the colon (ICD9, code 168) who met the and willing to provide a urine sample, and during each study subject's lifetime, as
                        sameresidence,language,andtobaeoouse the proportions were similar for cases well as other exposures associated with
                         criteria as cases and were frequency (81 .1%) and controls (E44 .3°6) despite dif- lung cancer . Exposure to ETS was ex-
                         matched tothepse series by 10-year age ferences in health status . As in the origi- amined by source during childhood (fn-
                         guup mrd raee. This control group wae nal report, subjects in the case and con- ther, mother, and other household mem-
                         selected as a means of assessing ieeall or trol groupswhose cotinine%reatininecon- hers who lived in the home for at least 6
                         responsebiaeaseoaatedwitharecentdi- centrationexceeded100nglmgwereex- months) and during adult life (spouse,
                         agaosieofeancerorwithbeingill.Inthe eludedfromthestudytoelimhmatepereons otherhouseholdmembers,oceupational,
                         report based on the first 3 years of case likely to be active smokers? Two (0 .6%) and socia) exposures) . Childhoodinchided
                         aecnal, the results were consistent for of356easesand26(2 .3R,)of1U&lcontrols theyea
                                                                                                                        .sfrombirththroughage18yearse case-cantrel compariaons using each con- had cotinine%reatinine concentrations of Expaeures from parents after that time
                         trol group Y This component of the study 100 nglmg or higher . Although no opti- were classified as other household mem-
                         was not extended into the fmal 2 yeara . mum concentration has been established bers during adult life, Dichotom,ous ETS
                            Lifetime smoking status was deter- as a cut point for distinguishing true non- exposure (ever or never) was examined
                         mined in a three-tiered approach . Infor- smokersfromsmokersinstudiesthatare bysourceandtypeoftobacco.Pack-years
                         matiun was obtained on each potential restrictedtowomenandineludesubjecta ofcigarettesmokeexposurefromepuuse
                          study subject's personal uae of tobacco, with cancer, a concentration of 60 ngfmg were calculated by multiplying the num-
                          first from the medical record of the can- or lower has been used as the eligibility herofpaoks smoked per day by the num-
                          cer rasees, then from the patient's per- eriterioninalargestudyofhealthy,free- berofyemsthespousesmokedoigarettes
                          sonal physician, and fuudly from the po- living suubjects!w and others have been while living with the study subject . Du-
                          tentialstudysubjectorhernextofkinfor suggeated?'es Inhighcxposuresettings, ration of exposure by source was mea-
                          thosepatientswhoeemedicalrecordsand urinary cotiuine in nonsmokers has suredinyears .Yearsofexposureinoo-
                          phyejeiane did not indicate a history of reached a concentration of 55 nglmg of cupational settings-repreaent the sum of
                          smoking. The telephone screening pro- cotuune/creatnnne'""Inth :satudy,nme years of employment in eachjob,in which
                          cedure(t8er3)wasslsousedtodetermine cases (2 .6'90) and 29 controls (2 .7%) had persons were reported to have smoked
                          lifetbnetobaecouseofthepopulationcon- urinaryconcentrationsof86to99ng/mg, around the study subject . Years of ex-
                          trol group . At the interview, the tobacco Analyses of ETS-related risk estimates posure from individual sources were ex-
                          use screening questions were repeated were also conducted using a cut point of amined, and asummary measure (smoke-
                          to confirm each study subject's reported 66 ng/mg of cotinine/creatinine as an ex- years) of exposure during childhood and
                          status as a lifetime nonuser of tobareo . clusion criterion to evaluate the possibil- adult life was calculated . Smoke-years

                          ,)PMA, June 8, 19B4-VOl 271, No . 22 , Tobacco Sntoke and Lung Cancer-Footham et el t759




                                                                                                                                                                                                                                 PM3006584829
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http://legacy.library.ucsf.edu/tid/pln86a00/pdf
                   years (72°k) with a similar proportion of         TaMe 4.-ASSOGalion Behveen Risk o1 Lung Cancer and Childhood Exposure to Tob9a•a Smoke Among
                   controls in this age group . As noted pre-        Nonsmuking Women•

                   viously,2 the age distribution in this se-
                   ries of famale lifetime never smokers with
                                                                         Evst SmuYeJ Tobeceo
                   lung cancer is older than all female lung
                                                                     Atl lung 4arWnomss
                   cancer cases in the Surveillance, Epide-                                                    30,10603              e69/1225           0 .85 (0.7o-1 .03)       6.es (U.67-1 .az)
                                                                       Father
                   miology, and End Results (SEER) Pro-                                                          76824               16111240           0.93(0.69-1 .24)         U85(o.62-i .18)
                                                                       Mother
                   gram, 1978 through 1986.4H
                                                                       O6rer household mem4ere                  131/617              269/1253           0 .99 (0.79-1 .25)       103 (0b0-1 .32)
                       The largest proportions of lung cancer
                                                                       Any househdd member                      377/606              808/1238           0.8g (0.72-1 .07)        o .e9 (0.72-1-10)
                    cases (58.6%a)'and controls (61 .1%) were
                                                                     Adenorsrcinome
                    white. A larger proportion of cases were           FsBrer                                   2391486              66an225                0.87 (0.704A7)       0.82 (0 .664 .04)
                    self-identified as Asian American and liis-                                                  601480              161r12<0               0.96(0 .741 .32)     U93(0 .65-1 .29)
                                                                       Melher
                    panic and a smaller proportion as African
                                                                       Other housenoiE members                   9a471               269/1263               0 .96 (0.74-1 .25)   0.99 (0.75-1 .3g)
                    American (blacks) compared with cun-
                                                                       Myhouseholdmember                        2901469              80e11238               0.e6(0.69-1 .07)     0 .85(0.08-1 .09)
                    trol6 . Approximately 42% of cases and
                                                                     omer nhrolag6al types
                    8g%of controls reported an annual house-           Father                                    86/137              669/1225               0.77 (054-1 .10)     0 .82 (0.5&1 .20)
                    hold income of less than $2(1000 per year .                                                  161144               161/1240              0.64 (0 .49-L45)     0.61 (0 .32-1 .16)
                                                                        Molher
                     Comparedwith contro/s,htngcancereases
                                                                        OMer housshold memben                    3ffi146             28911253               1 .07/0 .71-1-81)     /3810 .77-1 .85)
                    tended to havealower levelofeducatiom
                                                                        Any household memeer                     W/137                609/123e              0.93(0.644 .34)
                     66.8% of cases and 626% of controls bad
                     no mure than a high school education .
                      Table 2 displays the estimated RRs of           cfioleaAdt 51ed io1 farMy Mskvy o1 f~ rKer,e M In lgn-fisk ~ ~ons . OR kates odds and emplo,ansMBmh ocuupall Indi Israllo Crly
                                                                      con6dence h96rrel .
                    lung cancer associated with ever living
                    with a spouse who smoked by type of               Table 5.-ASSarAalion 8elween Risk of Lung Cancer end Childhood Smoke-Vefirs of Exposure Amcng
                    tobacco . A 30'% excess risk associated           Nonsmoking WnmM1 (Ssa-respondents Only)" _
                    with tobae/w, use by spouse(s) was ob-
                                                                                                                                                      Crude OR                   Adjusted OR
                    served for all histopathologic types of                  Chikheod Smeko-Yesrs
                                                                             olRoussehWdEZpcesra                Cases           Connole                (95%Cq                      (95%Cp
                    lung cancer combined (ar)justed OR=129;           A91ung rarclnomss
                    P<-06), for adenocarcinoma of the lung              0                                         148              444              1 .OU       . . .            1 .00    . . .
                    (adjusted OR=128 ; P< .05), and for pri-             1-1) ~-                                   95              291              0.98(0 .734 .32)             0.99(0 .73-1 .35)
                    mary tung rsrcinomas other than adeno-               a16                                      146              4e5              0.90 (0.70-1.17)             0.96 (0.67-1.16)
                    earcinoma (adjusted OR=1.37; P=.18).                                                                                             Trend P-_.5e                 Trend P-.36
                    The only individual types of tobacco as-          Adonoesrelnema
                    so ciated with significantly elevated risks         0                                         12U              444              1100                         1 .00
                    of lung cancerare reigar-and pipe-smoke              I-07                                      73              291              0 .93 (0.674 .29)            0.92 (0.654 .29)
                    exposure for bronchogenic carcinomas                 >_1s                                     123               4e5             0.9410 .71-1.25)             o.a9(o .66-1 .19)
                    other than adenocareinoma: cigars, ad-                                                                                            Trend Fs .66                 Trend Po .43
                    justed OR=1 .88 and P= .01 ; pipe, adjusted       Other NsMbglE91 ypee
                    OR=1 .79 and P=.02.                                  0                                         28               44C               00         . . .           1 .00    . . .
                       The estimated Rlts of lung cancer as-             1-17                                      22               291             1 .20(O.W-2 .14)             1 .32(0.72-2 .41)
                    sociated with pack-years of exposure to              z16                                        23              485             0 .75 ((IA3-1 .33)           0.86 (0.47-1 .54)
                    spousal ETS are presented in Table S .                                                                                            Trend Ff.33                  Trend P. .56
                    Inereasing risk of lung cancer with in-
                                                                        •Ad7uoted tor egs; rece; aWCy ares ; eduC9lion; lnilt6, vegetetlm, end supplemental Wtwnln InEax ; dleuvy
                    eren.sing pack-years of spousal ETS ex-           eIwl8Wam1; lamlP/ hlnory of Wng oancer. and employmenl in hlgh-rlsk occupetlans .OR Indlcslee odds reCb ; CI,
                    posure is observed for all lung careino-          conMknse mtenel .
                    mas combined and for the two histopatho-
                    logic subgroups. The risk estimates are            increasing duretion of smoke exposure                              stricting years of ETS exposure during
                    similar within the histopathologic sub-            during childhood . Childhood smoke-years                           childhood to those from the mother yieided
                    groups; however, the trend is significant          were unlmown fora large pnoportion (21P/o)                         similar nonsignificant trends .
                     only for all lung cancers combined (P= .03)       of the lnterviews with proxy respondenis                              Table 6 presents the estimated RRs
                    and pulmonary adenocarcinoma (P< .05).             and for 5% of the interviews conducted                             associated with adul t ETS exposm+e (ever
                    When the analysis was restricted to self-          with the study subject . For these inter-                          exposed and years of exposme by indi-
                     respondents only, siml7ar estimates of            views with data available to calculate                             vidual sources during adult life) . Eleva-
                     risk of lung cancer were observed with a          smoke-years, 64% of proxy respondent                               tions in risk are associated with inereas-
                     trend of incre.asingriak of lungcancer at         interviews vs 38% of direct study subject                           ing duration of exposure at home (trend
                     increasing levels of exposure (P= .08) .          interviews reported no exposure during                              P=.11), on the job (trend P= .001), and in
                        Expusureto ETS duringchildhoad and             eldld}tood. The data presented, therefore,                          social settings (trend P= .002). The in-
                     adult life firom multiple eources waa evalu-      are for analyses restricted to self-respon-                         cressedrisk oflungeancer amongwomen
                     eted. The rieks of lung cance.r associated        dents . No differences were observed by                             ever exposed to ETS during adult life in
                     with household ET3 expasares durmg                pathology review atatus ; dietary choles-                           the household is 24% in occupational set-
                     childhood as aresult of father, mother, or         temlintake;levelaPthefruits,vegetablea,                            tings, 39% ; and in social settings, 50% .
                     other household member smoking are                 and supplemental vitamin use index ; age                           The pattern of response is similar in the
                     shown in Table 4 . None of the RR esti-            group; or educational attainment. Black                            two histologic subgroups ; however, the
                      tnate6 significantly difrem from unity . The      study subjects had a twofold elevation in                          tests of trend are statistically significant
                      association of cumulative years of house-         riskinthehighestexpoemmeategory,and                                only in the largest subgroup, puhnonary
                      bold exposure to ETS during childhood             Asians showed twofold reduction in risk                            adenocafrinoma.
                      withlungcancerriakwas evaluated(Table             at this level; however, these two point                               As shown in Table 7, when all sources
                      6). No increased risk was associated with         estimates did not significantly differ . Re-                       of exposure to ETS during adult life are

                                                                                                                            Tobacco Snwke and Lung Cencer-Fonthem et al 1768
                      JAMA, June 8, 1994-Vol 271, No . 22




                                                                                                                                                                             PM3006584831
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                    Table e .-Assualatlan Between alek of Lung Cancer and Adult Eapnsures to Cigarelte Smoke Among eonsidered joitltly,atatisticall,+laignlficealt
                    Nonsmoktrip worrren- increasingrislolwithincreasingduration
                                                              aes., oa+sa4                                          ofexposureareobservedforalllungcan-
                                                                                                                     f
                                                           No eqm" Na F.xposam                 CNaa oa             au)uema oa
                                                                                                                    cers combined (trend P= .000t), adeno-
                                  oumnoelty saurca,_r      Naoeeasea waaes"u°Is                 (ssx,a)              tesx'c0
                                                                                                                    carcinomas (trend P=.001), and for cell
                                                             An wns Candaomo                                        types other than adenocarcinoma (trend
                     NouseMla exposwa (sOOUSS anE dher)
                       eversxaosee                            soaresa salnzs3   117 (0 9a-t on 1 zs (0.ae-+ sn      P=.05) . At the highest level of exposure,
                       0                                        1ss     ae+     100               1 .00             a76%increasedriskieobserved .Sirmlar
                       1-1s                                     184     as3     o.es(o .TSVZn + .1o(aeal.as) .      andstatisticallyeigniAcanttrendsinrisk
                       +a-ao                                    1as      244    +z3 (om-1 .aa+ + .a3 (asen.em       are observed with analyses restricted to
                       >30                                       173     295    + .z3(o.at-t .s1) 1 .28             ge][reapondentsforalllungCanQerscom-
                                                                                    Trend raoe       Trene ~.11     bined and adenocarcinomas . For other
                                                              aWas.   sslnzs3   11sta~-tss) 1lsroealszl             histological types, a eigliffi',ant trend is
                       [veremosm
                       0                                         11s     sz1    1.m              1 .00              no longer observed. Similar positive
                       1-is                                      13a     393    099 (a7a1 3z)     100 (8 .n-L<2)    trends were observed regardless of pa^
                       +sao                                      +oa     zaa     1.za to.91n .es) ..zs (o.sa1 .re)  thology review status and within all lev-
                       >30                                       135     zes     1ze (cas-+ .rz) 1 .zo (o.e7-1 .as) els of the fruite, vegetables, and supple-
                                                                                    Trean ~_.aa       rre.d rs .17
                                                                                                                    mental vitamin use index; dietary cho-
                                                                                 1 .11 (0 .7a-1 TM°°s lesterol intake; age; and rsce; although
                                                             otlis' NI°+"I°sl`°1 .64) +s1(0.952.3s)
                       EyqaWasep                               1¢p15a 9,1111243
                       o                                          W      ~+      1 .00             1 .00            theriskestimatesandtrendaweresome-
                       1-1s                                         45           3w         aela.el-1 .63)        1 .a9ra.99-a.3zl          what stronger among white study sub-
                       +sao                                         35           244        +21 (o.ra+ .9e)       1 .w (aoz-z .7n           jects and women youngerthan 70 years .
                       >3G                                          3e           2515       1 .0s (o.es-1 .rs)    1 .31 (a7e-z .zs)           To determine whether risk associated
                                                                                               Trend rs.s3           Trend rz.s2            with adult ETS exposure differs accord-
                                                                    Lu" ~n"n"`
                     ocwpaHUnel ewosue
                                                               al                                                                           ing to childhood exposure status, the data
                       s omoso aesrrsls 75611247 1 .1z(o .e1-fasl 1asn .+1-1 .7a+t were stratified by childhood exposure
                       a      a2C           491            + .ao voo (Table S). Elevated rlsks associated with
                       ~-15          213        450        1 .oa/o.e3-+.3a) +.90HA1-1bnt adult ETS exposures were observed in
                       1e50                   11a 223 1 .1e(o.es :(as) 1 .eo(1.oal .esx women with (trend P= .01) and without
                       >ao                     sa e3 . 1 :a3(o.~2 .os) 1 .esOSa-z
                                                                                           .7e)t (trendP= .0005)childhoodexposures,but
                                                                         ..os rrem r
                                                                                         .ao+ the elevations in risk for women exposed
                                              aasnocsrcmoma rrena A
                       s.v,,,,sse aowass 7senznr 1lewes-1an 1as(++a+esls duringcluldhoodwereabouttwiceaehigh
                       0     1ss          401          100                  1 .00 asthosewithoutchildhoodexposures .At
                       145         1e7         460         1 .lorosa1 .az1 1as(1 .oz-r .rs)t the highest level of exposure (48 adult
                       16 .30     93      a2s       +aaro             .sal .en 1 .w(+ .oes.os)t sarkoke-years ormore),anad,lustedORof
                       >ao                     ae       83    1 .es (o.ssals) 1 .e7 (t1s-z .sz)# 325 (96% CI, 2.42 to 7.46) was obaerved
                                                                 rre .ar>.os rrenare.oo+
                                                                                                  among womenreporting childhoodex po-
                                                              OU'® M`(Oft1c° T"0° - ass(ass.lssl + .ze(o.as-+ .ee)
                                                                asrlaa 7serlaar                                                             sure compared with 1 .77 (96%CI, 0 .98 to
                        kYSr srmeea
                        0                                            59           aa1        1 .00     ...        + .oo     . ..            3.19)forthosereportingnoehildhoodex-
                           +-15                                      as           a'm        oes(os7ze) 1 .1Bro .rasz)                      posure.Theeatimatesbasedonself-re-
                           1fi-3D                                    zs           223        o9s(os7-s3) 11s(ose-zoa)                       sponsesonlyindicateasimilarpatternof
                           >30                                       u             a;+       1 .eo(a7s-z.s3) z.oo(+ .oza.9o)t               rlskAlthoughthediffereneceareapproxi-
                                                                                                Trena raez Trend P= .sa mately twofold, the CIa for the ORs at

                      socw sW s,T4
                                                                ^a Lung    Candn"'"'°           each level of exposure overlap.
                           evere>mespC                      1am s           29'n200 +<Yn1a+ .]51t 1 .sot1 .14+ .BBla
                           o              aza                 947                          1 .00                 10o               COMMENT
                           1-1s                         110       177  1 asn .ro-tamt                              1 .esn ~ iss)t In this report, the RR of lung cancer
                           19.3p           <9       se      181/107-a   311t                                        + sa n .as-z.amt
                           >3a                                31 52   1 .33 (o~ Po .~ 1
                                                                          ~                                        nse to.os¢             ted with E•PS exposure was as-
                                                                                                                                   .~ sessed for all lung cancers, adenocarci-
                                                                  Ae~l~                                                               noma of the lung alone, and other histo-
                           E,reemosea                            ta7ieos zsrnzaa              +.aen .+sl .eau vs3n .lo-+ .e»t         pathologiccalltypescombined .Through-
                           0                                      3a       947                1m           + .ao                      out, the increased risks associated with
                            ++5                                      ea            1rr        1 .ao(+as-i .esx      1.asn .o~-i .97rc adult ETS exposures were quite conais-
                            1r,ao                                    41             ea        tnn .1a-zsnx          1a1 n .1e-z.mi-   tent for adenocarcinoma and other cell
                            >30                                      zz             sz        1zo(o.7aa.oe)         1.asro>z+-zss)
                                                                                                TrenO F.006         Trerq W.ea2       types an d,aearesult, foralllang cancers
                                                               bills, ypwoglcw                                      I" combined . Compared with adenocarci-
                            e a,musea                           aznae xemaw 1 .asrosa-tssl                          1 .ae(eao.z .oel  nomerases,thenumberofothercelltypes
                            0                                        104           so          1 .00    .           1 .00    .        was quite etnall; therefore, the failure to
                            1.15                                      ze            1n         1 ,34 a/.a5-R+z1      142 10.85,22s,   observe statistically significant trends in
                            1f4lD                                      7              se       oea(o .az-z .os)     o .esros7a.1s1    this groupis more likely a result of lower
                            >30                                        9              52       lse(o .aea2s)        1ae(e .ea-aa1)           atstistical power than biological differ-
                                                                                                 rrena rtz3           rrena w.+e
                                                                                                                                             ences in response in the two histopatho-
                                                                                                       :tw l to ogic detect aubgm up s .anups  power
                                           ~ ,~er,~er'M 9M ~neM NV~~~ 02+11one ~ In~~cel6s ~ Odre
                                                                             .                    wrma
                       1s1d~', ~°B(s°p oi~ 1sn+H I~eaOa CI~"aOR of For 1.3 example, the associated with
                        ~                                                                                                              .      ,
                       ~t~ .               ever           use              of       tobacco                           by              a     spouse                was         ap-
                            Yr'~o1 .l .                                                                                                      pro+dmately739ofora0lungcaneercases,
                            g ac.uo
                       ~¶3reehdal~e~asure is defined es sapuWre of 2 ur more hours per wsek trom snumss olh® san oocupstlunsl         and
                                                                                                                                             ~ll typesm~b'm~edo. Iu the 3-year report

                       1756 JAMA, June 8, 1994-Vol 271, No.                22   Tobacco                Smoke          and           Lung       Cancer-Fonthem                et    al




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                    ofthestudy,increasedl9skoflungcancer                                               Table 7.-NSSaNaBUn Between RISk of Lung Cancer and AdulOmOC Smoka-Yeem nf Exposure among
                    from adult ET8 exposure was stronger                                               NonemUtln9 Wamen`            .

                                                                                                       AduN BmokeNesre                                       CnuleOR                     Adlusted OR
                    for adenocaronoms of the lung than for all cell types combmed? That fmding is no      of eaposum           096ee      Conirae        (95x c/J                          (95%CI)

                     longer apparentwith the additional esaea                                                                     AN Wng Carc)rromaa (All Reapondente)
                     of each cell type . Although the estimates                                        0
                                                                                                       _                         48            118           1 .00

                     of RR for pulmonary adenocarchwma are                                             1-11                      74            239           0 .76 (a6P1 .16)           0.s2 (0.52-1 .29)
                     not different from those for other cell                                           1&z8                      13N           307            1 .11 (0.75-1 .63)        1 .12(073-1 .70)

                                                                                                       2&67                      153           304            1 .24 (0.841 .82)         1 .35 (0.89-2.04)
                    typesfarthe predominant cell type diagn6sed . 248                                                        163               285             151 (1 .03-223)t         1 .74 (1 .142.66)t
                    in women with kmg cancer who are life-                                                                    '                                  Trend P<.0001            Trend Pa0oo1
                    tbae nonemokms, and so the effects of                                                                          wdeneearckloere (All Reepondenta)
                    ET6 exposure may be particularly rel-                                  0                                  36               116             1 .00                    1 .00
                    evant for this histopathologie cell type .                             1d1                                54               239             0.74 (0 .46-1 .19)       0.74(0.d4-1 .23)
                    More than 75% of the cases in this study                               12-28                             110               30!             1 .17(0.98-1.61)         lA5(o.7&1.83)
                    were diagnased with primary pulmonary                                                                    112               304             1.21 (D.78IXS)           t .xaro.91-ao4)
                                                                                           29d7
                    adenocarcinonla, twice the proportion of                               zu                                130               265             1 .81 (1 .05-2 .47)7     1 .T/(1 .1z-2 .e0)t
    Vol . 271        adenoearanoma of the lung diagnosed in                                                                                                       Trend P=.0002            Trend N .0001
      1994           all USwomenwithout regard to smoking
                                                                                                                              oaror Nlatolugieal Types (All nespondentc)
                     Idatory: 37% among female lung cancer                                                                                                                               1 .00
                     caees in the SEER program'O In other                                  0                                    12             118              1 .00
                                                                                           1-11                                 20             239              0 .92(0 .~~, .74)        1 .17(0 .52-2.62)
                     studies of ETS in female nonsmokers in                                                                                                                              1 .00(0  .4&2 .18)
                                                                                            12-28                               28             307              0 .80(OA4-1 .82)
                    . which histopathology was reported, ad-
                                                                                            29-47                               41              304             1 .33 (0.87-2 .81)       1 .58 ().763.31)
                     enocarcinoma comprised 00% or more of
                                                                                            z48                                 33              265              1 .23(0.61-2.4(I)        1 .76(0.93-3 .75)
                     all cam in six of nine etudies .'"''aAu'i" In
                                                                                                                                                                     Trend FL.12              Trend P.05
                     the otherttree studies, the proportion of
                     adenocsrcinoma /a(se,s ranged from 48%                                                                  All Wng Carclnomea (SeN-reapoaderds Only)

                     to 64%>a1a1 Differencesinthe physical and                              0                                   3o              119               1.00                    1 .00

                                                                                             1-i1                               53              238              0 .86(0.51-1 .54)        0 .79(oA4-1 .42)
                     chemical properties of sidestream smoke
                      comparedwithmainstreememoke,includ-                                    1226                             103               306               1 .32(0.042.10)         1 .2010.74-1.94)

                      ing the distribution of the vapor and par-                             29d7                             110               30i               1 .42(0 .90-2.25)       1 .44(0.89-2 .31)

                      ticulate phaees and the concentration of                               z4N                              105               265               1 .58 (0 .88-2 .47)      1 .67 (7 .032 .70)T
                      known or suspected csranogens:' cpm-                                                                                                           Trend P=.002 Trend P=D006

                      bined with diffetences in inhalation, nasal                                                                AOa11YCarCmlana (BeIHe6pOnd9nte OnP/)

                      vs oral, may yield a higher proportion of                              0                                  23               116              1 .00       . ..         1 .00      . . .
                      perlphe.ral alten0e8r0inOn1N8 ~                                        1-11                               41               Z18              0 .88(0.53-1 .44)        0 .81(0 .4&1 .3T)
                          Mieclaeaifieation of diseeNe status was                            12-28                               98              306               1 .48(0.89-2A5) .       1 .31(0.77-2,22)
                      minimized in this study by the eligibility                             29i7                                82              304               1 .38 (0 .83-2.30)      1 .39 (0.62-2 .8e)
                      criteria (microscopie diagnosis required)                              x48                                 91              265               1 .76(1 .08-2.92)1'      1 .85(1A9-3 .15)t
                      and an independent review of diagnostic                                                                                                         Trend P= .001           Trend P= .11005
                      material that was completed for 85% of                                                                ONer Nldologieal Typee (Nelf•rHpontleMe Only)
                       the cases. The small proportion of esses                              0                                     7             118               1 .00
                       found ineligible by independent review                                                                    12                                0,05 (0.33-2 .22)        0.91 (034-2 .45)
                                                                                              1-11                                               2311
                       may result from the populatkm-based tu-
                                                                                              1 ~B                               15              308               0 .83(0.33-2.08)         0.82(0 .31-2.18)
                       mor registry affiliation of four of the five                                                                                                 1 .555 (0.68-3.65)       1 .64 (0b7-4.03)
                                                                                              2.9-47                             26              304
                       eWdycenters.Theconeisten(y ofthefmd-                                                                                                         o.e9(0 .35-2.z8)         1 .1zto.42-z.98)
                                                                                              e,46                                14             265
                       inge with and without nonreviewed cases
                                                                                                                                                                       Trend P- .49             Trend P= .32
                       Bupporta the contention that thestudy
                       results were not meaaurably altered by                                    Wueted for age; rece: study urea: educstlon; imlte, ve9eteblea, and supplemenlel vHemin Indes ; tlialary
                       inclusion of ineligible cases                                           eboletorol ; femlry Mstmy nl lung eaneer, end employmenl In N9t .dsk ompellona OR Indkates odds ratla CI,-
                                                                                               CEnadeRC9 hd9nem.
                                                      . M' 1===tFC~tionofeveramokemaslife-       tP<05.
                       time never smokers is more problematic .
                       The objective of this study was to evalu-                                  A higherr proportion of controls than                 actively smoking and less likely to be re-
                        ate the riskof lnng eancer in women who                                eases was excluded from the study as a                   vealed than healthy, free-living controls.
                        had neversmoked . Atpresentthere isno                                  result of elevated concentrations of nri-                Other data suggest that lung cancer eases
                        known biomarker of fifetime tobacco use .                              nary cotinlne/creatinine, 2.3'% vs 0.6%.                 who are ever smokers may be leas in-
                                                                                               Cases were identified at hoepitals, and                  clined to misreport smoking status than
                        Cotinine, the major metabolite of nico-
                        tine, is the most widely accepted bio-                                 scresning oF medicaf recordN and physi-                  others in the generalpopulation : the pro-
                        marker of current (1 to 2 days) tobacco                                ciaoB about the patdent's eurrent and past               portion of ever smokers mieelasaified as
                        exposure and is useflil for distinguishing                             use of toba(xo preoeded the sereening by                  nonsmokers by discordant reports was
                        eurrent actrvestnokerafrom currentnon-                                 telephoneandattheinterviewforaAstudy                      1% among female lung cancer cases from
                        nmoketN'," The proportion of reported                                  eubjeeta. This procedure may have elimi-                  five case-control studies and 6 .7% among
                        nonsmokers in the:p3+esent study with a                                 nated some current emokers fmm the case                  subjegtsfromgeneralpopulationstudies!
                        cotlninelereatinbte concentration above                                 series who would have been inclined to                   Neither cases nor controls were informed
                         100ng/mgwas 1.8%, thesameprgPOrtion                                    self-report as nonsmokere in an interview                before the interview that a urine Nample
                      . with a concentration above 100 nghng                                    format. Alternatively, some cases who                    would be requested toellminate the op-
                         observed in a 10-country, multieenter                                  would misrepott smoking status may be                    portunity foravoidanoe of personal to-
                         study of self-reportzd ETS e       .xposure.He                         less likely, because of health status, to be             bacco use or substitution of :specimens.

                                                                                                                                               Tabaccu Smoke and Lung .CanGer-fpntham et al 1757
                         JANN. June H, 1994-Vol 271, No . 22




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                      Tab1e 8 .-Associstlon Bshreen Risk a Lung Center end Adulthood Smoke-Yesrs Among Nonsmoking Women With and Without Chtldhood Exposures•

                                                                      NoChllRrooEE>tpneure                                                             ChllAhoodE.poeure
                       BmoKe•Yaeraot                                                                    ----1
                      Eap09YrepuAne                                              CruEe DR -            Adjusted OR                                             Crude OR                 Ad}ustetl DR
                         1MWNOo6                Cases        Controls             (115%CI)               (9575Cf)            Cases         Controls             (95%Q)                    195%C)
                                          -                                       All luna Carc8wnue ve Controls (All Reepondents)
                      0                           33             71           1 .OD     . ..          1A0 , . .                  6             44           1 .00     . . .           1 .00    . . .
                      1 .11                       33             91           0J8 (0 .43•199)         0.78 (0.40-1 .43)        38              13r          1 .53 (0.66-3.52)         1 .63 (D,69-3.88)
                      12-28                       41             97           0.91(0.52158)           0.80(0A9-1 .C8)          88             202           2A0(1 .08-5.30)       .   2A3(1 .07-5.51)t
                      2947                        54             97           1 .20(0.71-2AQ          1 .t8(0.65-2 .06)        a5             204           2,28(tA4b.07)             2b4(1 .18-8.01)t
                      zA8                         64             80           1 .45(0.85-249)         1 .77(0.98-3.19)         94              182          2 .e3(/ .29828)           3.25(1 .d2a.48)t
                                                                                Tiend Pm .04            Trend f3 .01                                         Trend 1=.0013              Trand P= .0005

                                                                               An LuWiq Cercinomae ve Controle (aetFrespondents Only)
                      0                           23             71           1 .0)      . . .        1 .00    . . .             5              41          1AD      _ .              i .0o
                      1-11                        23             90           a79 (0A1-1 .52)         0.69 (U.34-1 .36)         29             137          t .e8 (e .89-5 .10}       1 .85 (O.aaS21)
                      12•28                       28             97           0.89 (0.q-1 .87)        D.6C (032-128)            69             2pi          302(1 .15-7.93)t          2.99(1 .11$05)t
                      29<7                        3e             97           7-05(0 .e3-2 .10)       1 .04 (O.SY1 .98)         87             204          2.89 (1 .107 .59)t        3.33 (1 .23AA()t
                      ei8                         31             e0            120(0 .84-2 .24)       1 .36(O.B&280)            70             182          3.39(1 .29-e .99)t        3.03(lA/-1o .42)1 .
                                                                                Trend P=26              Trend Ps.17                                           Trend P=.004               Trend ~.001

                        .Adlusled ior a9 e ; recB; sCUCaBUn; sluCy &sa; tmlls, ve9elaMSS, an0 supplemenim W lamin In Cmr, tietery cTOtesf¢rot ; i&ml0' hlslory a Nng cnn cer ; ana emplo'menl ln N9h-rlsk
                      occupalbn . OR IMiwtee odds rafiu,; CI, conedence intervel .
                        iPG.05.



                       Refusal to provide a sample was similar                        series and among self-respondents only                    in preliminary analyses . The final model
                       among living cases (1996) and controls                         suggests that systematic misclassi5ca-                    ineludesanindexthatcapturestheintake
                       (17%); however, because of ilbless and                         tion by proxy respondents for adult-life                  of both dietary and supplemental antioxi-
                       death, a higher proportion of the total                        ETS exposures was minimal .                               dants and a variable for dietary intake of
                       subjects in the case series had no cotinine                       The inconsistency in the literature with               cholesterol adjusted for calories . In this
                       measurement .Of study subjecFs for whom                        regard to the association of hmg cancer                   study, high intake of fivits and vegetables
                       no sample was available, 63% reported                          with ETS exposure during child-                           and supplemental vitamins is associated
                       ever having lived with a spouse who                            hood~7.1'-sieicixn may stem from the lim-                 with decreased risk of lung cancer, and
                       smoked; for study subjects with eotin¢te                       ited power of many of these studies, as                   dietary cholesterol is associated with in-
                       detem161ations, 63%of eligtble women and                       well as difficulties in recall of distant                 creased risk• Although it has been sug-
                       68'% of excluded women reported ever                           events and/or incomplete knowledge by                     gested that low intake of carotenoids or
                       having apousal ETS exposure.                                   proxy respondenta. The effect of each of                  ftvits and vegetables and high intake of
                              Analyses using a lower cut point (65                    these factors is likely to vary among dif-                dietary fat are potential confounders of
                       mg/ng) for exclusion based on urinary                          ferent cultures, as well as by the propor-                the association between ETS and hmg
                       cotinine concentrations provided slightly                      tion of proxy respondents in any given                    cancer,'stlliswas notobservedinonrstudy
                       higher eetimates of risk associated with                       study. Failure to find an independent eY                  or in the recent teport by Halandidi et
                       ETS exposure, but the differences have                         fectofcluldhoodexposureincase-control                     al's In addition, similar trends of incareased
                          little or no effect on study conclusions .                  studies might result also from the latency                riek of lung cancer aesociated with increae-
                             Compared with recent large US stud-                      period of lung cancer and the age distri-                  ing smoke-years of exposure are appar
                          ies, the proportion of proxy respondents                    bution of female nonsmokers with lung                      ent at all levels of both dietary cholesterol
                          for kmg cancer rases in this study was                      canee . Lung cancer arising as a result of
                                                                                             .r                                                  intake and the index of fruits, vegetables,
                          small : 36.9% compared with 65% in the                       childhood ETS exposure would be ex-                       and suppleinental vitamin use . Household
                          study reported by Brownson et al9B and                       pected to occur relatively early in life .                radon was measured by 48-hour passive
                          67% in the study by Stoekwell et al ."                       Even with a latent period of 30 or 40                     diffusion canisters in a sample of study
                          Nevertheless, itis importlutt toevaluate                     years, these cases would be younger than                  subjects' homes, and these screening 1ev-
                          whether the findings differ when proxy                       60 years at the time of diagnosis, and                    els in all five geographic areas were uni-
                          respondents are excluded from the analy-                     such ebses comprise a small part of the                   formly low and not associated with case-
                          ees. The only appreciable difference was                     total case series . No differences were ob-               control status. These observations indi-
                          noted for childhood exposures .(H'those                      served in this study, however, when risk                  cate that the strong association in this
                          interviews with proxy respondents, 31%                       associated with smoke-years of exposure                   study between adult ETS exposure and
                          were conducted with the study subject's                      during childhood was examined for sub-                    kmg cancer risk cannot be attributed to
                           spouse and A8°lo with an adult offspring                    jects in the case and control groups who                  any likely confounder.
                           of the study subject . These individuals                    were younger than 60 years compared                          A poeitive dose response between ETS
                           had lived with the study subject and                        with those 60 years of age and older. Al-                 exposure during adult life and lung can-
                           shared life experiences during the study                    though no independent effect of child-                    cer risk was found when individual sources
                           subject's adult life, but not during the                    hood exposure was observed, such expo-                     of exposure, such as household, occupa-
                           study subject's childhood years . The op-                   sure appears to modify the effect of sub-                  tional, and social settings, were exam-
                           portunity for misclaseification of expo-                    sequent ETS exposure during adult life .                   ined separately, and this pattern of risk
                           sures is greater, therefore, for childhood                  Twofold increases in risk are observed at                  was clearestwhenthese exposure sources
                           exposures . The lower reliability for child-                all levels of adult exposure for subjects                  were considered jointly . The point esti-
                           hood exposures compared with estimates                      who had any childhood household expo-                      mates are somewhathigherfor exposures
                           of exposure from a spouse has been noted                     sure compared with those who did not .                    in occupational and social settings than
                           previously.'s,`' The consistency of find-                       Individual nutrients and micronutrients                within households, but these differences
                           ings for adult-life exposures in the total                   assoc+ated withltuig cancer were included                 are not statistically signi8cant. The higher


                          1756 JAMA, June 8, 1934-Vod 271, No . 22                                                                             TODacco Smoke and lung Cancer-Fontham at al




                                                                                                                                                                              PM3006584834
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                  e8tAnlatRe In the former eettange tftay re- 0 . Aldba ]D, Rsf R, Blot WJ. Passive emoldug 2g . ButlerTL . The RelnNoreahfy ofPaesioa Smnk-
                                                                                                  . Cancer i+w to Vo.,:oua Hed.u& a,atemnw Aanong setewh-
                  f1eM ehSnce, some reQll bias, or the po- and lung c+neer among Japanese wmran
                                                                  . 1~,98Y18n4d8Pl.     Dag      Advertists ;n Catifarn ;m Los Angnlew Dm-
                  tentiat for a r number of smokers Rt'
                               l~~                       4 .9rowneonRD,RaifJS,Ree®Td,FerguaonBW, veraityofCeliPornia-LosAngele41988.Theeie.
                  and .ettmkeellp0aut•e8111t11eseeettlllg8. Prite1JA.Riekfsetarzaforadenoeatrinomaofthe 29 .GuTmkelLTimetrendsin7ungeancermMdity
                  Workplace E1S expostlre bae received lang. Am J EpidemiaL 19b7 ;1x6?aS4. among nwmnmkera and a note on passive Nnoldng .
                  lesg attention than domestic ETS exfw- fi Bugler PA, Pickle LW, Masnn TJ, Contant C . J Nel[ Career, fnat 198181981-1066 in no~nuhling
                                                                                                                                           .
                                                              ~~ees of lung cancer in Texea Im ADeeU E4, 80 . ximysma T. Cancer morLtity
                  SUI'e in studies of 1un6 cancer to date; Correa P, eda Lunp Caneer. Causes and Pr¢ueu.- womenwithmooldngk
                                                          .                                                                   .ebendahoaedonaluege ses[e
                  howeVer,tllonitoflftgofE'1 S oritaCoin- tbn.NewYork,NY :VerlagChemielnte .naHarel eohortstnd.ymJarpan.AwMSd1534;13:B8a890.
                  Btituent6illWolkpingtlSettlllg5handeftY Inr,1994P3'99.                   31 .RoteD7,CiIliaCR,ChapmC,HawthorneVM .
                  onatrated detectable markers of ETS by ~ Hnn~gitAng.~c ndm~amt ea c m~ea~ g~e~raei pop~ulet on ut the w~eet of Scotla~nd EMi
                  p¢reonal ah• mnnitorklg and biomarkere pn'ya, VI : Carxer Ep'rdernioLogy. Stutigatt, Ger- 19t%Y99A23-0:7 .
                  with average toncentrat3on5 similar to many: Gustav Fiechei Verlag;198219?2V¢.                  32. Browneun RC, Alavmtja MC, Hock ET, Luy
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                                                                                                                                         hmg
                                                                  . Passave enwl6ng and lung amcerm f.¢aret 190% ing women .A•m.JPublie      .192X
                  mum values? In a study of Workplace W                                                                                                     .
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                      7Yda                                               .~~BChineeewomen .ErJConcer. 1~7¢ /,la~l~ hnad,CaUFlifetlmel.eamingPUbRta-
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                                                                       91 . Sveneean C, Perehagen G, IDmntnekJ . Smoh- 48. LeMarehandL, WRldneLR,HankinJH,Hdey
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                     Pew, 191111


                                                    .      22    Tobacco          Smoke        end      Lung       Cancer--FOnlhmn                   et     al    1759
                     JAMA. ,hine B,1994-Vol 271, No




                                                                                                                                                      PM3006584835
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                Dr Herbert and colleagues focus their comments almost ex-                                         The Productivity Costs of Providing
             elusively on testing the accused and claim that the policy would                                     or Withholding Treatment
             have adifferentialeffect on communities ofcolor . The existence                                      To the Editor.-Dr Eddy' has written yet another excellent
             of raeial bias in the criminal justice system is clear . However,                                    article . To be complete, the following principle should be
             these crititisrns should be directed toward the system itself                                        inserted (probably as No . 3) on his list:
             rather then toward our narrow policy . Otherwise, any public                                         Because ilineaarelated productivity losses have the same economic
             policy involving part of the criminal justice system nnret be re-                                    impact on society as direct health care expenditures, it is also valid
             jedzd as inherently biased. Moreover, our proposed policy is                                         and appropriate to consider the productivity-reiated costs of provid-
              earefullyconstructed to provide strict procedural and aubstan-                                      ing or withholding treatment .
              tive protections of the accused's rights, making it unlikely that                                      An optimally healthy workforce bestows a tremendous com-
              the politywill be "selectively"or"punitively" applied . Since evi-                                  petitive advantage . This has been recognized by armies since an-
              dence indicates African Americans are approximately twice as                                        tiqtuty(disease-relatedlossesexceededbattle6eldlossesinmost
              lHcely to be victims of sexual assault as white Amerieans (1 .3 per                                 wars), Irynations(thesuccess of the British navyin part through
              1000 persons aged 12 years and older, compared with 0 .6 per                                        theltse oflimee to prevent scurvy), and by modem corporations
              1000),' our policy offers potential benefits to many minority                                       (which invest in the health of the workforce) . While this liters-
              vrolnen and men who are assaulted                                                                   ture is youllg and the measures of productivity and productive
                                                    . - Or Herbert and colleagues suggest compulsory testing of   capacity are imperfect, it appears that for many if not most dis-
              the accused will harm the survivor.111is is paternalistia Ad-                                       eases, the lost prodllctivity costs exceed th e tx,st ofinetlical treat-
              vocatee for survivors have long sought this information? Fol-                                       ment?These costs take many fmms, ranging from the disabling
              lowing our policy, only a smvivor's request triggers testing .                                      of a laborer with back pain to the disabling of a country by an
                 Our policy does not presume that survivors are seronega-                                         impaired leader" Consideration of productive txtpacity will pro-
              tive, nor does it pressure them to report sexual assaults to the                                     duce significant changes in the amount and type of care that is
              police. The Centers for Disease Control and Prevention guide-                                       recommended by Eddy's proposed deciaion-making process .
               lines specify that pretest counseling should be tailored to the                                        First, prevention will be favored because this calculation
               specific needs of the client and must include a personalized                                        will ascribe to most illnesses greater expense and, hence,
               client risk assessment? For survivors of sexual assault, risk                                       more justifitstion foravertingthe illness . In a recent example
               asseesmentwould includewhether theyhavepreviouslybeen                                               from JAMA," chickenpox vaccination cost twice as much ae
               tested for HIV and whether they have known risk factors .                                           treatment if only medical care costs were considered . How-
               Where survivors are also victims of domestic violence, post-                                        ever, ifthe economic loss of caregivers is included, the return
               assault services should include access to shelter , counseling                                      on the investment increased dramatically, from 0 .5 to 5 .0,
               about the ongoing risks of domestic violence, and advocacy                                          strongly favoring the preventive approach ."                    -
               assistance where requested .                                                                           This economic advantage of optimal health justifies the pur-
                  The potential impact of s positive test result on the accused                                    chase of more health care services of all kinds, not just preven-
               andtheriskof suicide are important considerations . ourpolicy                                       tion . Conversely, decreasing health care in ways that reduce
               would allow the accused to exercise the option ofnot receSving                                       productive capacity will cause financial resources to become
               the test results . The accused who chooses to discover his HIV                                       more limited and fewer health rare services to be affordable .
               infection status needs the same level of support and, if neces-                                        One implication of this, that care should be focused differ-
               sary, protection as do other persons who are tested .                                                entially on the productive members of society, may seem dis-
                 Like Herbert and colleagues we strongly support the pub-                                           tasteful . However, if we take a long view of productive
               lic health goals of voluntary HIV testing with pretest and                                           capacity, a human capital approach, the future contributions
               posttest counseling. The real question, however, is whether                                          of the young and the economic contributions of homemakers
               the HI V community, as a matterof political and public health                                        will be fairly valued . And, if properly weighted between the
               orthodoxy, will always reject compulsory testing regardless                                          productive and the economically dependent, this calculation
               of the justification, even where the policy is centered on the                                       should increase, not decrease, the absolute (but not rela-
               psychological benefit to survivors .                                                                 tive) amount of services available for those in economic
                         Lawrence 0. Costin, JD                                                                     dependency.
                        Georgetown University IAw Center                                                                       George W . Anstadt, MD
                         Washington, DC                                                                                        American College of Occupational
                      Zita Laaasrini, JD, MPH                                                                                   and Environmental Medicine
                      Harvard School of Public Health                                                                          Rochester, NY
                      Boston, Mass
                                                                                                                    1. Eddy 0. Principles kr maNingdihkult decisions in dif5eult times . JAMA. la9i ;
                . Diane Alexander                                                                                   217:1792,1798.
                       National VicfSm Center                                                                       2 GreenbergPR, atiglin LE, riNceletein aN, eerndt ER . The eeonomic burden nf
                                                                                                                    depreeeion In 1990 . J Cdn Pepchialry. 1993;69 ;406A18.
                       Arlington, Va                                                                                3 lbet JAt, R,bins Rs. ATen Itlneee Serikes nm IeMerTAe Dltemum of tke Cep-
                               Allan M                                                                              tive Eine. New Hu .en, Conn : Yule Univereity Preae ;1993.
                                      . Brandt, PhD Harvard Medical Bchool                                          i Lieu TA, Cnehi aL, 61sek Sa, et al. Cwt-eRectivenees ora routine vnricella wc-
                                                                                                                     dnetlan progrmn for U9 childrea JAMA 1999g71 :3'16291 .
                               Boston, Masa
                                                                                                                    Plais 7etler wm sRm~ to O . Eddy, ®Ao dectined lo repta. ED.
                               ICenneth H. Mayer, MD
                               Memorial Hospital of Rhode Island
                               Providence                                                                           CORRECTION
                               Daniel C . Silverman, MD
                               Beth Israel Hospital                                                                 Incorrect Date~in the Original Contribution entitled "Environ-
                               Boston, Mase                                                                         mental Tobacco Smoke and Lung Cancer in Nonsmoking Women : A
                                                                                                                    Multicenter Study," published in the June 8, 1999, issue of THR
                 l . suresu ufJuenro Staaetias . Crimina! VieEim(ratinn in [he United Sfatea,188P .                 JoURNAL (1994 ;271 :175&1759), an incorrect date appeared . On page
                 wasbington, DC : nureau of Juatice Stetiano ; l9&L2L
                 L Preeideatlel Cummieeion on the Human Immunodcfiaenvy Vime Epdemie .                              1752 in the third sentence of the "Methode" section, the date should
                 8csna! Areuua uM HN Tmnsmietan . $ V, chep 9 nt n-2B flem report eubmitted                         read December 1, 1985, not December 1, 1986 .
                 to the Preddent of a,e United States, 1989.
                 a CentWe MDlceaseCunt.olandPrsventlnn .`feeatdrsl yvidmree onA1V counael-
                 /ag. A1MWR dfer6 Metal Wkty Rep .199B;14{Nu. RR-2Y8-14.



                  1B7a JPMA, November 23W . 1994--Vol 272, No .                                               20                         Leners




                                                                                                                                                                                       PM3006584836
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