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Philip Morris

Association of Indoor Air Pollution and Lifestyle with Lung Cancer in Osaka, Japan

Date: 19900000/P
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Sobue, T.
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2023512516/2023513116/Ets: Lung Cancer Volume I 930900
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Inubusi, T.
Murai, Y.
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Center for Adult Diseases Osaka
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internaronai jovrna,i of _otdem,oiogv, 1011 '9: '-0 3' S~oo , c internauonai Ep,aemto/ogical Associat on 1990 Pr-teo n Great 8,ta- Association of Indoor Air Pollution and Lifestyle with Lung Cancer in Osaka, Japan TOMOTAKA SOBUE Sobue T iDivision of Epodemiology. Department of Field Research. The Center fbr Adult Diseases. Osaka 1i•3+3 Yakam, icn. Nigasninari•ku. Osaka 537. J3pan). Assoc ation of'indoor ain pollution and lifestyle with, lung cancer in Osaka. Japan. lhre.natronafJournal of Epidemiology 1990, 19 (Suppl 1): S62-S66. A.hospital•based case-control study among non-smoking womenwas conduetedd to clarufyriskfactorsin non-smoking females in Japan. Cases consisted of 144 non-smoking female tung,bancer patients, and these were compared to 713 non-smoking female controls. The odds ratio 195% confidence intervall for use ofiwoodbrstraw as cooking fuels wnen subiects were 30 years old was estimated as 1.77 (1.08 to 2.911: For those whose household members. other than hus- bands. had smoked. the odds ratio was estimated as 1.50 11.01 to 2:32). For those whose mothers had smoked. the odds ratio was estimated as 1.28 (0.71 to 2,31). Use of heating appliances did not show an etevated risk. Some points to be noted in the study of low-risk agents for lung cancer are discussed. In Japan. lung cancer was the second leading cause of' cancerideaths for mates and females in 1987. ' In mates. although, smoking rates have been decreasing gradu- allv since the 1970s. 61i°b of males smoke6 in 19R8. which is considerablv higher than in other developed countries. In females. however, smoking rates have been quite constant, since the 19'-;0s-ontv 13°0 of females smoked in 1988. whichlis low for a developed countrv: As a result. population attributable risks for lung cancer caused by smoking were estimated at71°b in males but onlti' 26% in females.= In the standard monalitv ratio (StitR)ianal}•sis of the geographical distribution of lung cancer risks. a higher Sy1R was observed in coastal urban areas than in inland rural areas for males, but for females no such tendency was observed.' This indicates that occupa- tional exposure and outdoor air pollution seem to have little influence as lung cancer, risks for Japanese women. Therefore. it; is necessarv to investigate nsk factors for females which, might be relate& to daily lifestyle. This study aims to clarify the risks of lung cancer caused by indoor air pollution among nonsmoking females by means of a hospital-based case-control studv. This work is parn of a joint project of the research group for lung cancer prevention in Osaka. The mem- tiers are liste6in Appendix 1. D vision ofEpidemiology, Department o6Field Rcsearch. The Center far-*dult Dfseases.Osaka.l-3-3 Vakamich Hi¢ashman-ku.Osaka:37 Japan MATERIAL AtiD NtETHODS Accordine to Osaka Cancer Registr%. '_481 primar% lung cancee( 1977 males and _50-3 females) pattents were diagnosed in Osaka Prefecture in 1985. Of these at;out, one-quarter were registered from the top etght hospi- tals. which have special departments for lung cancer. These eight hospitals participated in a, multt-eentre. hospitakbased case-controll studs' with the support of the Osaka Anti-Lun¢ Cancer Association. Both cases and controls were collected from those newly admitted to the eight hospitals from 1 January. 1986 to 31 December 1988. and their ages ranged from 40'to 79 vears at the time off hospitalization. Of the above eight hospitals. all ward's for lung cancer and one or two wards for other diseases were involved in this study. All newly-admitted patients. both males and females. in these ward's were investi- gated by a self-administered~ questionnaire at the time of admission to the hospital. A uniform questionnaire was used in allihospitals. designed specifically for this studv, which included questions about smoking habits. exposure to environmental tobacco smoke (ETS) and exposure to possible indoor air pollution.. A total of 1079 lung cancer patients and' 1369 patients of: other diseases were investigated for males. and '_95~ lung cancer patients and 1073 patients of other disease for females. Males were not included in this analysis. For females. there were 55 current smokers. 6-t ex- smokers. 156 nonsmokers and 20 patients with unknowmsmoking status for lung cancerpauentsr and S62 NOT1CE This mzterial' r,?a~ be protec~ed bly T@p law (T~tlz 17 US. C25;e),
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:,D0e'iR~>IR.POLlll rIr)-I ~ >~,D Li( ,(, ,~~ lM 'ER~~ a corresponding 1'1 9''.'~;ty and "(1 for patients of other diseases. re,pecti%elV. Anai'nsis w.ts focused on l~n nonsmoking female lune cancer patients as cases .tnd -~y temale patients ot other diseases as controls. N., mutchlna procedures Nere conducte& hetskeen cu>e~ and controls. There were I!' cases and'':~ contr;ols e\cluLled heL:au.e ~)i mi,>rnt! intoomaui)n on expo,ure. .At a re,uit. 11.1'ca,es .1n:1 3l controls comprised the total tor thl< •tuds. Adlu>ted odds ratw, %•ere calculateLd hv the \lantel- Hac n>zel method'- uane'tour levele ot.1_e cateeories .tti ,L/inisslun and t.at le%els oFeLiucationl Loeistli reeres- •ion :rnal%sls was performed including the cartahles %khlch sho%%ed ,i=nitiwnt increasz Ot risk in unicanate anal%cis.' R'E SL' LTS Alllcaszs were microtia.npicallc confirmed, and'had the tirllowinsz distrihution-adenocarctnoma I,.y°a!. >yu:rmous ccll carcinoma (3"O)'k small cell carcinoma j. laree cell carcinoma (A"o !. and other histologi- cal types Controls ~cere L1ia~,.nosed ashavine the tollowing diseases: breast cancer l4h°o). stomach cancer 1,1: ".). other cancers ( 16°o. benign neoplasms circulator.• diseases 1-V0). respiratory 'diseases infecttous disease (2°.) and di_eesti, e diseases Table 1 shows the distribution of aee and! edu} cational leveli for cases and controls. The mean aee att admission to hospitals was 6U'for oases and _56 for con- trols. Hieher education levels were observed! for con- trols as compared~ to those for cases. Table 2 shows adjusted odds ratios for lune cancer associated with use of wood or straw as cookine fuels according to the age at exposure. Significantly elevated risks were obsened for subjects 30 s•ears of aee who had used woodor straw as cookine'f.uels. Use off these fuels at age 15. showed a slieht increase or risk although it was not~ statisticalh• sienificant. When the exposed were defined as those who used these fuels either at aee l; or age :(). the odds ratio u as estlmated as I.2S ut¢h an 11-.i;1-1.,t7 confidence inter,al.. In the calculatloniot'the odds ratlo. the use of heat- in¢ appiiances-Lerosene. ~zas, coal. charcoall and %%oxod >to.es «Ithour chlmness µere reearded as poss- Ihle sources ot espowre u hich couid pull'ute Indoor alr kN Ith combu>non products. Electric air conditioners. ,toce, with chimness and electric :tones %%ere not re_ar&d as •ources ot exposure. There were nonsk eievationsohser,zd tor exposure at arn age (Table :). The charcoal foot warmer wa, populhrh usediuntil the 19MIs. hut is now rarelf, used in Japan. A2alni. risk ele- ~auon was not obser.eJ for zsposure at an% aez t Table Odds ratios for lune cancer, associated with ETS tlurlne childhood were shown hc source of exposure (Table i). A slivhc increase of risk was sugoested'' fari those " Ith smoking mothers. althoueh statistical ;iti- niticance was not observed. As reeardsETS in adulthood. an'zlevated risk was observed for those whose household members. other than husband's. had smoked (iTable b t. Smokers amone other household members consisted chieflv of the hus- band's father and sons. Table 7 shows the results of logistic reeression,analv- sis. includine the three variables in the model. which uere sugoested to raise the risk of lung cancer rniuni- variate analvsis. l:se of wood or straw as cookinLy fuels at aee +t) showed a risk 1.7 times hieher. with statistical si¢ntticance. The other two variables showed slieht'l,6 increase& risks, but were not statisticallv ~i¢niticant. The results from the same analvsis. when breast cancer patients (controls) were exclud'ed: showed similar results. DISCUSSION From the results of this studv, the use off wood or straw as cooking fuels was suegested as a: possible risk factor for current female lun¢ cancer cases in Japan. despite TaBL'E t' D/!/rlhuflon JIJEe a! Jd/nlSSlon Ynd%Yarso/.educalfon for uses und'c ontrolr CtlJraill'rlslli5 C./se Control V 4ee e[ .idmuiion .;IL:u .Il 139 _?S':'-.n, c1L-cv 19 ?1 u `_9 ?1 3 evt-,V -IL.'Q L _3h Years oiicduuuon tessthan YY n9 1' 9 '_:9' :1.1 Ill~iro.er . .'-.I !n` ruy 7 T.aLE . Odds rarnos;iurlune canroussoctaeed n trh'duusenl ~ood or vrau as cnokuig,n.els uccordinq to a¢e ot rspocure Case•Controt OR (9?"o CI') Aee 14 V:) . j9r_ht I IM) Yts .ij,1'll I..J tU.N(s-1 at I .>ee t/l'NO. 11_h041I t.1q Yes -_ 1 LS9 I t. l tl-: l lh f Ptesent Nis. les t11'7j1 II. I I tr) 'Conndenceantercal
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SO•t! f',TER\ a71O', rL JOI.R\-kL OF EPIDE.-1/IOWG1 !iL PPLE\Il ". , T.eue.:' Odds rut,os.rorl:.ny.cancrr.usoaarrd I uh the,uere hratrng ryutpmrer; polluung room,iu - +nc Comeusvan proaucrs: .ucurdingto ./.1r Jt LLj7uSLrr C.tx{ontroi OR tu:', Cl' i ~u I :,, :n._nI I ,n lr>, .u t ,,l tn n~l _1. n In tu <I_1. _) Pr;.ont. nirl l:r 1-1'?_ t ll i1,---t Nn 'C.+nndenee inl its being an old practice. These types of cookin¢ fuel'ss were widespread until the 1960s even in suburban areas. but now very few people use them even in rural areas. Of those who used wood or straw at 30 vears of age. y0°o had also used these cooking fuels at 15 vears of age. This indicates that those exposed'at age 30 must have been exposed'for a longer duration. It is reported4hat use of cooking oil. especially rape- seed oll, increased the risk of lung cancer among Chinese women inShanghai-`In the same report. how- ever. the use of cooking fuel including coal, gas and wood did not show an elevated'risk of lung cancer. In Hone Kong. the use of kerosene oil as eooking fuel appeared to increase the risk of lung cancer among Chinese womemalthough the effects of these factors seemed to be limited.' It is also reported from Sin• ¢apore that there was no difference of risk for lung cancer between those who used wood or charcoal and those who used petroleum or gas.~ However, all these reports provided information concerning Chinese women who practice different methods of' cooking from Japanese women. Also, in these studies. the exposure from cooking fuels were defined as ever ver- sus never or were based~on only recent status, and the TABLE 4 Odds ratios for lung cancer assocrared wh' the use of exposures ,:ariable ma% not'corrzctlv reflect the status oil pasntxposure. Infactn when ever ~ersusnz.ar an.,l- ssts µas used. ;he use of wood'or straw as cookln_e tuels did notishow a significant ele.atwn of risk. In the present studv. no,one was found who usts wood or straw as cooking fuels at present. so this does not constitute a factor for primary prevention in Ihts countrc. Howe%er. this showed that the en%lronmzntul exposures occurrtne 20 s ears :rgo could affect the inci- dence of lung cancer. which in turn means that some lifesnles µidespread anpresent can be risk factors for lune cancer in the future .tlthough conventional apl- demiological studies cannot rzsesl these factors at present. It has been reported that some compounds found in wood smoke-benzo(a)p~rene and formlldzhsde- are possible human carcinogens.' It has been shown that, the aromatic fraction of wood smoke. which con- tains various polycyclic aromatic hydrocarbons haN mun3¢enie activitv.' AIsot the polar fraction of oreanic extracts from emissions of wood'combustion has been shown to have direct mutagenic acttvitv: " It is reported that, natural inhalation exposure to wood' smoke increased the incidence of lun¢ cancer in mice. The use of heating equipment for room air. includine kerosene. 2as. coal. charcoal and wood stoves without chimnevs, did nocshow an elevated'rlsk oflun¢ cancer. Of these. charcoal and kerosene was most freque'ntly used atiaee lh and :0, respectt.ely. Wood was used for heating fuel only for less than 5ao of the population. therefore the risk due to wood stoves could not be eval- uated. It is reporte& from Hon¢ lhon¢ that the use of kerosene stoves increased the risk in women. = In lapan, nolincrease of risk was observedifor the use of kerosene stoves." ETS from. the mother during childhood seemed to raise the risk but did not show statistical si¢nifieance. It has been established that ETS for children increases the occurrence of lower respiratory illnesses. particu- T.eLe '; Odds ranos lor lung cancer associated .wh entvnnmrntal .hareoal foot warmer7 Jorstteprng according to age arrrposure tobacco smoke Jurxng chrldhood b% source of r.sposure CasetControl OR 195`s C1' 1 CasuComro4 OR 045% CI'1'. xge IS' Na 911,470 1.00 F3ther smoked No 351143 I t10. Yes 53!?61 1.01' (0.69-1 48) '. Yes luti)r588 q.79 111 Aee 301 Mother smoked No 112/616 1.00 No 1_''66lI 1 Ikt Yes 3?J115 1.05 (0.66-1 68) '. Yes 17/ 63 I 33 t0:"4-- '-.3'1 Present N0 1s3.7`5 1-00 Other household members Vo 1131587 1 .110, Yes 11 6 0.67 10 09-5:1'-1 Yes 3.W44 1 18 4 0.'6-11 tu9 'Conedence ,nterval. 'Confidence ,nterval
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I\ DOOR aIR POLLLTIO"w-k~D LL\GC.a\CER T.sie h Oddsraaosjor /uny cancrr ,usucmrnd +uh rnvronmentalro:+ucco smokern ididihood b% sourcr of erpusure. Casc,Consrol C~R ru5"o Cl") HUshand >mu.rd .. ~?_6 wn Fcs n IB n-i'-1 n?t Othcr hou>ehoW memrcrc`V Q1 tGU Yt•> 1 I'At) 1 il.r_:?lt1 'Cunriddnce rnter%jI larlv early in life. and increases the frequency of chronic respiratory symptoms, '`4 Its relation to lung cancer. however. has been less clear. It is reported that the odds ratio for lung cancer associated with exposure to a smokinQ mother for nonsmokin¢ females was 1.7 in the U.S.`"'and .4'.U in Japan.' ~ Concerning ETS in adulthood. ETS from the hus- band did not show an elevated' risk in this studv. In lapan. a-;0-10(J°b increased risk for lune cancer associ- ated with ETS from the husbands was reported1° `" although some studies found no increase.' It is esti- mated from the meta-analvsis dealing with two cohort studies and ten case-control studies that the increasedI risk of lune cancer by ETS from the husband would be ,0°b.-" In the present studv. ETS from household members other than the husband showed an increased risk of lung cancer. This is consistent with a report from Japan that ETS from the husband's father elevated'the risk of lung cancer 3.2 times,' Some methodological problems should be con- sidered in this studv: First. a substantial proportion of controls consisted of cancer patients. especially breast cancer. Although use of cancer controls has various merits and demerits.=' it is obviously not appropriate to use controls from a single disease. When breast cancer was excluded from controls. the odds ratios for use of woodIor straw as cooking fuels, ETS from the smoking mother, and ETS from household'Imembers other than the husband became 1.65. 162 and 1.47, respectively, whichIdid not show substantial change. Second. smoking status of the study subjects was investigated by self-administered questionnaires and no validation was conducted by other objective means, such as testing for cotinine in urine or carbon monox- ide in expired breath. However. these methods cannot be applied to determine smoking status in the pasnonly to recent smoking status. Further studies are needed in this area. Third. the exact duration of intensity of exposure could not be investieated'for use of cooking fuels and ETS from various sources of exposure. However, S8= detailed information obtatned fromI indivtd'ual memorv mav not be reliable enough taIconduct dose- response analvsis.-- Fourth. no systematic review for histopathological diagnosis was carned oun. but routine pathologv reports were used. l+lowever. since all'W pathologists involved in!the elght hospitals were specialists in lung cancer and had worked at least five years in this area:. validitv of these reports were thou¢ht to be quite high as f.ar as the determination as to whether io was malig- nant or benignL The analvsis in this studv was not con- ducted by dividing lung cancer into histological types. and it is believed the effects of this onIthe results would be minimal. There are some epidemiological points to be dis- cussed in the study of low-risk agents. First. subjeccss were limited to low-risk individuals for lune cancer. which in this study were Japanese females who had never smoked. It is generallv thought that focusing on low-risk individuals can strengthen the association between the disease and exposure.=' makine it easier to find possible associations. except when positive inter- actions exist. Secondly. whenme categorize the study subjects into exposed and non exposed! it is important to pay atten- tion to the timing between exposure and' disease. According to the mechanisms of earcinogenesis. this appropriate time difference will varv: For example. if the agent in question acts mainly in the early stages of carcinogenesis, there should be a longer latency time betweem exposure and disease, but if the agent acts mainly in the later stages. the lag time between expo- sure and disease will be short. In this study, exposures were defined according to the patient's age, and were able to reveal the association between cooking fuel and lung cancer. H'owever, if we use ordinary classifi- cations. such as never-user versus ever-user, or present use, the association would not be seen. Thirdiy, even if we can use the appropriate classifi• cation ofexposure. considering its timing in the occur- rence of the disease, it is important that the population has the appropriate diversity in terms of exposure classification. In other words, there should be some proportionI of people who will be classified as non- T+.Le 7 Odds ranos eatimared by logunc regresslon analvru. A drurtedYor age ar hosp.edizauon. Vanabl'e OR (95% Ct'). Use of wood or straw at age 30 Other householtl' members smoked in 11.77 (1.0&-2.919 adulthood 1.50 (1.01-2.~J.) Mother smoked in childhood 1.28 (0.71r2.31).
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Sfa) I\TER\aT1O'--kL;.1OLR'\aL,)FEP1DEs11OLOC;f jLPPLEsI£\P,!i exposed together w'tth people who K,ll be classthed as. ,:.posed. This is not alwa%s the c lse in the situation of cookinc or heatinepractices, for which most people ahare aicummon tratiition.,Iln lapan. there hate been .frasttc:hanizcs in liliatclz since \Lorld War ll). Sanitarc cundit!ons: in most houses Were not rer,_' euo& in the t'y:l'K. hut have dramatically tmpru%eti in the lari!k. and (hls can he re~!arded as an appropriate non- e.paset! ~ttuation. Mixed practices in cooking and heating uerz pre\al'ent during this transitional pernod between the 1950s and 11980s. w'hich, provides a good opportunity to identify a low-risk agent for lung cancer associated with d'nil\, liiesttile. ACKtOWLEDGEMENT We would like to thank the late Dr Shizuo Okada for his conoribution to this study. \Ve also thank Ms N. \*akaVama. Ms T Inubusi and Y'Murai for their tech- nical assistance. REFERENCES Statuncs unJ'Informauun Depanment. Minrster s Secretariat. S1in- s:rc at Health and We!fare. l,tal3lansucs tw17Jupan. Tuk.o. lufi9. Sobuc T. Suzuki T. Horal T!. I Istsuda Nl. Fupmoto I Relauonship hetv.cen ilgssra:te smuktn¢ and hlstu!o¢re t\pe of tun¢ianuer., ~uhcpccralreferencetusetdttference JpnJCJinOncul,lQd8: I8: '-13 The Research Committee on GeographtcallD,stnbuuon,)i,Drsease. \anonal Atlas or motor dtsease mortaltnes rorcurrs, ro-ns and t,llaees in Japan All causes of death. cancer. .ardio•as:ular diselses, dubetes mellttus. licer cirrhosis and'tubercu!ostsd luh'o--1978. Jjpan He:rlth Promotion Foundation. Tok.o. INR'_. Breslow N E. Da. N E. Staersrrcal'merho+Lr in cancer rrseazch. The un.ii.sls of .•ase-control smdics IARC scientific publications. wl 1. IVRII; L.on,France.. 'Gau Y T.Blut: W J. Zhen¢ W:,er al Lumt cancer amun¢_ Chinese women. In, J Cancer 1987. 40: NJ-t-9 Koo L C. Lee N. Ho J H-C: Do cooking fuels pose a risk,for lung cancer' A case-cuntrol studt of v umen i Hong Kone Ecology of Disease 1983: 2: _'5--b8. StacLennan R. DaCosta J. Day N E. Law C H. N¢ 1'K. Shanmug- aratnam K. Risk factors for lung cancer,m Sineapore Chinese. a populatlon with high female incidence ntes. InrJ Cancer 1977: 20: 851-'+?bIJ: Pierson W E. Kocninit J'O. Bardana E J. Potential adverse health effects of wood smoke. w'esr J.Ned 1988. 151: )54-i_: '%tumford7 L. He X Z. Chapman R S. eral: Lun¢cancer and,ndoor air pollution in ?6uanVei; China. Science 1yk7:.2J3: `-1"~__U: >ltfictm I. Ramdahl!T. Contnbuuon of wood combustion to indoor air pollution as measured by mutagemcatn in salmonella and poWcycltc aromatic hydrocarizon concentratwn. Ens:,ron Nutagen 198.t:6: I.o-A:. L,an¢ C K. Ouan N Y. Cao S R. He X Z- Ma F`atural inhalation c,p.•,ureto:wl mo.ke and w.a•J ,m„At.mJu:ur.unc...,n•rr in mtie.and r,usBwmrdEmu,.n Sa, I: Lcune 1 S M C:aratc,mu4in,t :he :erv.cne ,t.,•e ind lunc.in,er in Hbnd'h•,n¢ BrJ.D1s Chr.st, jhinutu H. >:asccontroii-tud•.ol ;une _un:cr h•.hnt,,U1_c" It,p L:me (.,n,r, !ux?. _J: 'L) Dc;.,r'mentoI.He.,ith and Human Punllt. H.'Am )tr,tieOthie Sm,~.,np widldrdlrh~ Phr .ir,rm•~ntp. ,t,-na •,hcrr,n,n,i :unr.lr,ru•r Y.rc^,+rt `I th: •urtemm ~e•tcraii \1,r,hinct',n. DC US G,•crnmerll Pr,nlin. (-)ince. -1 DHHSi PHS ru:, rt_i : - L S Dea.irtment •,t H1+jith and Human 5orn~x.,. Punuc H:.,.~th, O1n:e's,rl•,rs,n~! J,Itt lir,ldth, rhrnrJ,al,1..,a,,t :nr„Luudr• -1A rc,^.vt ,•1 the •ur._e••n 1% ,,,h,nctoni DC L S Gr,sernmcnt Pnntrne ••Inie. 1lu A H. Hender.rn B E. P,ke. M C. lu \I C jm,•n,ne ino '.~Ihcr rl•k uet.•r, wr iun_L can.cr in women, J\athl,lu ~ . `a: jhimtzu H. Tommae;t S. %,~h,mura\1. 1_ rit.t A C,•mt`jri-n •'t dintiu-cpiJem,uiasetcal feature,.,I ;unr cancer ^.,Ircll• ..,tni and w+thout a ht,tur% ut ,m.,king' Jpn J C!rn t la,,r, :u•_. IJ:, cut ti_h4r 'Hlr:r,ama T`on-,makin¢ w,se>.u he.rs, ha•z a rnk...•t lunl cynier a,luJ. Irum Jupan: BrNr.i J: :: . :J:: '.Aklb,tj. K.ttuH-BIot.W I Pjsot•c',m.,kmNrs:nJ:un¢:.,mi.•r.,m,,nti Japanese wr•men. Cancer Rrs: W,~O. 46: =u~" Blot W J. Fraumenl J F Paasne >mut.m,t and iun¢ ;,,nccr J~.ul C'miter lnsr'1Vrh. 77:.w?-l,M:st _ - SmtthA H, Pearce N E. C.,Ilas P\\ C.rnccr:j>.•-:.,ntr,•i'.tuJic,•.,tti other cancers as.ontrols: lnt J Epr.lrm:.d 17: "Kulonel L%. Hirohata T!. \omura A .\1 1Adcuu.,cv,,t ,urnr+Jut.l collected tromsubstnute re,pundeno. .an 1'Epr.lem,••L;Q-". 106: 1"i,_t.t . Lerchen %1 L. Samet J M ?tn asscssment,a the ..,I,dit•,,tr,tue,t,.,n- natres rrsponses pwadcdi:+. .rnur.,.,nz •p,tux -Ane J'E:,,- Jemo/ur ly.M. 1'_J: lkl-4 "RothmanKlLFuoleC. i;trenethenm.prognmmetorwejw ;rnons:. lnr J'Eprdem,o7 1 ut+6. 17: u$>-y<4 APPE`'DIX I Research ¢roup for iun¢ cancer preventton in Osaka Tumutas.:rSohuc. MD. Tak.uchtroSuzukt. bID. Minoru %1St.uJ:r. MD . Osamu Dou MD'. Takashi Morl- %1D- Ki.u•uk, Furuse. MD . %tasahtro Fukuoka. N,lD':..T>utomu Yasumrtsu. %ID~. Osamu Kuwvh- ara. `1D'. Sf,chio Ichitant. MD'. Masahtko Kurata. SID' %lasa..ronu Kuw abara, MD'. K.uusa Nakattara. MD': Shuzu Endo. %1D'. F:enrn Sawamura. ytD'. Shon Hatton. MD-- The Center for Adult Disease. Osaka. :' Japan National Kinki Central Hospital torChest Dise:rses. .4`11!J;tpan Osaka Prefectural Habtk,no Hospital. 4?al Japan National Tune.,ama Hospital. 5Ml Japan 'Osaka Red Cross Hospital. 412 Japan ' Tazuka Kofukai Medical Research,lnstrtute. 53UJapan, K.tnsa, Denr.ok} Hospital. S537apan First Department ot Surgcry, Osak Lnm.erstas Medical Sch,wi. ~5? Japan -Osaka .intLun¢ Cancer Assoclatton, t.il Japan

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