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i »y, Inr, J' Cunc-era0, 6pa-609'11987) 198? Alan R. Liss. lnc. . N c ' : E R1s ~;,tori3l tr'3`J bE protected by w)Bm Iaw IfiUt 17 , U.S. Cod.1. P.D!rc.trorps rnt ~^te•nst~or~~ unro~aq:~.~s+~~^ce• PuD!.catror- atr.Unrdn imitrn~t0n~r[ ..JnOrr~t.l.anc,tr. LUNG CANCER AMONG CHINESE WOMEN Yu-Tanp GAO'. William 1.,BLOr'. Wei ZHENG!. Abby G. ERSHOw", Cheng Wen HSU3 . Lynn l,. LEvfs'. Rong ZHr+nGl and Joseph F. FRrcLaENL. 1R.' 1 Shanghai Cancer Insriiure. Shanghai, People's Republic of Chirw: 'Narional Cancer lnsrirure, Berliesda„ MD 20892, US.1: and 3Shanghar Chest Hospital. Shangliai, People's Republic of Chirta. A case-control study involving int.rviews witlr f72 fomalW lung cancer patients and 73S population-based contTOti was conducted to invcsti=ate the high rates of litng canc*r, notably adenocarcinoma, among women in Shanghai. CiSarette srnott- in= was a strong risk factor, but accounted for only about on.- fourth of all newly diagnosed nses of lung canca.. Most pa- tients, particularly with adlnocarcinonu. were life-tong nor+- smokers.. The risks of lung cancer were hijher among women reporting tubcrcukasis and other pre-a:istinj lung diseass. liormonal factors were suuested by an increasad risk associ- ated with late menopause and by a gradient in the risk of adenourcinoma with decreasin= menstrual cycle l.n=th, with a 3-fold excess among women who had shorter qrc/es_Perhaps most intriguing werc associations found between lung cancer and measures of exposure to cooking oil vapors. Risks in- creased with the numbers of meals cooked by efther stir frying, deep frying or bo:Gnj; wiM tlie frequency of smokiness during cooking; and with the frequency of,eye irritation dur- in= cookinj. Use of rapeseed oil, whose volatikts following hi=h-temperature cooking may be mutagenic. was also r.- ported more often by the cancer patients. The findings thus confirm that factors other than smoking are responsible for the hiYh, risk of, lung cancer amon= t.hinese woman, and pro- vide clues for further researcti, inciud"g tdie assessment of cooking practices- The age-adjusted annual lung cancer incidence rate amongg females in Shanghai during the 1970's and 1980's has been about 20 per 100.000 population. one of the highest rates in China and in the world (National Cancer Control:Office, 1980; Gao. 1982; Waterhouse er al., 1982: Shanghai Cancer Regis- try: 1983). Eievated' lung cancer death rates have also been observed among Chinese wotnrn in other parts of the world. including Hong Kong (Kung et al., 1984; Koo er al., 1985). Singapore (MacLennan er af.. 1977) and the United States (Fraumeni~ and Mason. 1974. Hinds er al:, 1981; Green and Broph., 1982). The high rates of this cancer are surprising since few Chinese women smoke cigarettes (Deng and Gao, 1985). Funhermore, in Shanghai (Zheng and Gao. 1986) and elsewhere. hospital records have indicated that most of the lung tumors are adenocarcinomas. a type of lung cancer less stronglv related to smoking (Lubin and Rlot„ 1984): To explore rt:asons for the high rates of lung carr:er among women in Shanghai. the Shanghai Cancer lnstitute, in collaboration with the US National Cancer lnstitute, carried out a population- based case-control investigation. Herein we report the results of this study. quantifying the role of smoking and evaluating a variety of suspected risk factors. MATERIAL AND METHODS All newly diagnosed cases of primary lung cancer (9th Revision 1CD 162) during the 2-year period February 1984- Fcbruary 1996 among female residents of urban.Shanghai aged 35-69 years were identified by a rapid reporting system for lung cancer established for this study. The system was built upon the existing Shanghai Cancer Registry, the oldest in. China: (Gao, 1982). Trained staff contacted medical' facilitiess in Shanghai' to ascertain new eases: so that interviews could be rapidly scheduled (typically within; 2 weeks of diagnosis). The staff reviewed~ relevant medical records, abstracting data on the basis of diagnosis. histologic type, and the site of the tumor within the lung. Two senior pathologists and 4 senmonr clinicians were appointed to review the diagnostic information from alll cases collected in the study. including X-ray films, cytologic and histologic slides. Female controls were randomly selected within 5-year age strata from~the general population of the Shanghai urban area. The number and age distribution of the controls were deter- mined in advance from the number and age distribution, of lung cancer cases reported to the Shanghai' Cancer Registry during the period 1980-81. The selection procedure involved randomly choosing a neighborhood' committee from among the approximately 1,300 committees in urban Shanghai, then randomly choosing a household group within the committee and ascertaining fromtxisting rosters the names of all'.females in the appropriate age range. Among these persons. 2 were randomly selected. If the first was absent during the period of study or could not be interviewed. the second was accepted as a control. Tables of random numbers were used' in the random sampling. The cases and: controls were interviewed; by trained inter- viewers. A structured questionnaire was used to obtain infor- matiomon demographic characteristics. exposure to tobacco: dietary and'cooking practices. medical conditions. familw his- tory of lung cancer. menstrual and reproductive factors. job history andlother variables A1l'completedquestionnaires and medical abstracts were checked by a field~ supervisor% and the information was then abstracted on coding sheets for kc.- punching and computerization in the United States. Statistical' analvses of the collected data were based on mul- tivariate techniques for case-control data (Breslow and' Day. 1980). Logistic regression analyses were use& to ~ estimate summary relative risks (RR) of lung cancer associated with various factors, after adjusting for age (<55, 55-59, 60-64. 65-69). smoking (non-smoker; smoked less than 20 years or less than 10 cigarenes/day; smoked 20 or more years and 10- 19 cigaretteslday; smoked 20 or more years and 20 or more cigarettes/day). education (no forrrta) educacion. primary school, secondary school and higher) and other variables. artd to evaluate statistical significance. Population attributable risk (PAR) estimates for stnoking, adjusted for age, were also derived (Whittemore. 1983). RESULTS A total of 765 lung cancer patients were identified' dunng the 2-year period' and interviews conducted with 672 ('88 % ). We excluded the 93 patients who died, including 3$ ascer- tained by death certificate only.. There were no patients who ~i refused interview. Forty, three percent of the cases were diag- Q nosed by tissue biopsy. 38 % by cytoiogy, and 19 % by repeated N . CJ Addn:ss repnnt requests from China to Dr.. Gro and from other coun- u trxs to Dr. Bloc . Recetved March 30. 1987 and in rrvised:form May 29. 1987.

LUNG CANCER 1% CHINESE WOMEN 605, TABLE 1- RELATIPE RJSKS'OF LU%G CANCER ASSOCtATEDW'iTH NUMBER OF CIGARETTESSMOKED PER DAIAND DLRATIO% Or SMUKI~GDuni,m ol'm~np - -- - Vumber of~.arucnef. snqYee ptr~.d+~ eX9.YesrS~. > }G ltu. Cur, Corwrob RR' 9SR,CI Casr• Convol• RR v'~ CI < 10 36 45 1.4 0.9-2.2 34' 29 2 4' F4-4 1 10-i9 19 11 2.6 1.2-5.7 56 33 3.2 2 0-5 1 20- 13 2 8.9 2.0-40.2 78 10 14.1 7 1-.B 0; 'Adlusred fm are r.dedwcauon !:or.smoken art used;u th rekrercr Itroup. 7A6LE 11.-RF1.ATtvE RlSKS OF LUNG.CANCER,AMOHG WON-SMOKING WOMEN ASSOCIATED WiTH:.YEARS LJVEt).wt7W A.SMORINGHUSBAND Yea„ 1„.ed,,.„,, ,,,,i,fti,~„p,,,a C,.n C=.,*: ta +s. CI <20 57 qg 1 0 _ 20.29 63 93 1.1' 0.7-t.8 30-39' 78 107, 1.3 0.8-2.1 ~t 40 48 76 1.7 1.0-2.9 'AAlustedfor aRe ud eduacwn ~ X-ray films. Among the 542 interviewed cases pathologically' or cytologicalh- diagnosed. adenocarcinoma was the predomi- nant celll npe acccwnting for 611% of all cases. 22% were squamous carcinomas, 6% wese oat-cell (or small-cell undif- ferentiated ) cancers. and I1. % were mixtures and other cell i types. A total of 735 controls were interviewed. Among these 71 (9.79<) were "second" controls. chosen mainly because the firsnselected control had moved from the Shanghai urban area or was found1o be outside the eligible age range. The distri- butions by age. education and rnarital status were generally similar between cases and controls_ More controls than cases (32 % vs. 20 % ). however, were in the oldest age group of 65- 69 years. but all subsequent analyses were age-adjusted. Cigarette srrtoking, Cigarette smoking was associated with a significarttly in- ~ariskoLlung~cec:0vea,dtpttgils.oNy3S,% .of't3te lung c~ncer paiien), , (camp.Md;ats~18%w of the controls) had ever srnoked. Therc was a 3.3-fold excess risk (95% Cl - 2:5- 4.2) of lung cancer among smokers, but risks were higher for squamous-cell carcinoma (RR = 7.2, 95% CI = 4.6-11.1) and oat-cell cancer (RR = 7.2. 95 % CI = 3.6-17:0) than for adenocarcinoma (RR = 1.5, 95% CI = 1.0-2.1). The RR for all lung cancers combined tended to rise with increasing num- bers of cigarettes smoked per day and with increasing duration of smoking (Table 1). The excess reached 14-fold for females who smoked 20 or more cigarettes per day for more than 30 Years. Similar trends existed for adenocarcinoma and for squa- mous/oat-cell cancers, but the magnitude of ttte increase was coruidenbly greater for the latter (not shown).. We calculated population-attribuubk risk (PAR) estimates for amoking in each agcgroup : The PAR rose with age, from 8% to 27% to 28% to 40% at ages <55, 55-59, 60-64, and 65.-69. respeccively, primarily because the prevalence of smoking rose with age. In total, we estimated that 24% of all female lung cancers in Shanghai were due to smoking. Passive smoking No significant increase in risk was observed for overall exposure to environmental tobacco smoke during childhood (RR = 1.1, 95% CI = 0.7-1.7)~or adult life (RR = 0.9, 95% Cl = 0.6-1.4). For these calculations, exposure was sai& to Occur if the subject had' ever lived with a smoker. When exposure was defined in terms of husband's smoking, . how- ever, lung cancer risks among non-smoking women tended to increase with the number of years a woman lived with a husband:who stnokedr the RR r aching 1.7 among those with 40 or more compared to kss than 20 years' exposure (Table D). The risk in this heavily exposed group was even higher (RR= 2.9. 95 % Cl = 1.0-8.9) for squamous- and oat-ce11 carcinoma• Previous lung diseases Since lung cancer in its early stages may be confused with other lung diseases, we excluded non-mallgnanr lung diseases occurring within the 3 years preceding interview'in evaluating the effect of prior lung disease upon lung cancer risk. Table III shows that previous tuberculosi's. pneumonia and emphy- sema were significantly associated with lung cancer risk even after adjusting for smoking. Although some individuals re- ported having 2 or more of these diseases. the excesses for each persisted when those with multiple conditions were ex- cluded. Further analysis (not shown) indicated thar the effect of tuberculosis was not related to the use of isoniazi& or streptomycin. While tuberculosis artd pneumonia were related to both squamous/oat.-cell carcinoma and adenocarcinoma ofi the lung. emphysema and chronic bronchitis were associated only with the squamous- and oat-cell types. CodJng practices Soybean and rapeseed oils were the oils used~ most often for cooking in Shanghai. with over 95% of women reporting the use of both products. Rapeseed oil. however, was reported as the most often used cooking oil by 52% of the cases compared' to 45 % of the controls. The overall increase in risk associated with ~ rapeseed compared to soybean as the most often used' oil was 1.4 (95% Cl = Table IV shows that the excess lung cancer risk associated~ with use of rapeseed oil existed at each level of reported frequency of eye irritation when cook- ing, a subjective variable representing severity'of exposure to cooking vapors. The calculations for this Table excluded the few women who never cooked, and employed as the reference group women who most often used soybean oil but never or rarely reported eye ii•ritation. Table IV also shows that risks of lung cancer were independently related' to eye irritation„ with the highest risks (RR = 2.8, 95% Cl - 1.".3) among those using rapeseed oil and frequently reporting irritation. The patterns were similar for squamous/oat-cell, cancer and' adenocarcinoma. We also observed, after adjusting for eye iiTitation, a 60% higher risk for lung cancer among women who reported considerable or somewhat smoky conditions inn their homes when cooking. another rough measure of exposure to cooking vapors and to house ventilation (Table V ), !n addition, the risk ratios increased with the number of different dishes per week prepared by stir frying. deep frying. or boiling (Table VI). In contrast. no significant case/control differences were associated with the type of fuel used for cooking. The RR and 95% Cl associated with coal., gas and wood' as the usual fuels were 0~9 (0.7-1.3). 1.1 (0.7-1.5). and 1.0 (0:6- 1.8) respectively. There was tw trerd in, risk with increasing years of use of coal. the most common cooking fuel in Shang- iA

606 GAO ET AL TABLE 11I - RELATIVE R.tSKSOF LL'wG CANCER:ASSOCIATED1MiT.H PREVIOUS:LCNG DISEASES' Pau 16nr dncaxs. Comrolf. All ca~ses RR' 95111 CI' Squamwi uace~~ RR" 9S* CI Adrno- urcanortu RR' u54 None 554 418 1.0 80 1.0 - 229 1.0 - Tuberculosis 61 80 1.7 1.1-2.4' 20 2.0 1.1-3.7 42 1.6 1.0 2 5 Pneumonla Emphysema 35 18 65 37, 1.9 2.0 1.2-3:0 1.0-3.7 16 19 1 8 4.5 0.9-3'.8 2.0-10.3 26 6 1.5 07 09i27 0.3-'-.0 Chronic bronchitis 86 112 1.2 0.8'-1.7 35 1.4 0.8-2.5 33 0.8 05-1.3 M ithout emph~ sema Others 30 30 1.3 0.7-2.2 8' 1.7 0.7-4.2 13 1.0 0.5-2 0 I All r,sEk diuued for ape. educatan ad srtqYtn{ ard''rdanve to .•ornenWtth.non reported pnorlunR'dueaae. Persorss wph moce.dun one past lung diaease areincluded tn eacti lungdisease cateForr.. TA1t-EtV - RELATIVE RLSKS.OF LUNG CANCER,ASSOCIATED ~w1TN COOX1wG OIL USED MMOST OFTEN AND FREQUENCY OF EYE IRRlTATION WHEN COOKING. TABLE V - RELATIVE RISKSOF LUNG CANCER ASSOCIATED wITH FREQUENCY OF EYE [RR)TATIONAND HOUSE SMOKIyFSS'wHEV COOKI%G Eye nrwoon Wien cooLmg OQI ueC moa un- Caaa Coccaia RR' V71t CI Eye ir.wuon Houae amotln<ss Ca.es Ce.urdtRR' 95% CI. Never or rarely Soybean 140 214 1.0 - Neverrrarely None/slight 244 380 1',0 - Rapeseed 145 193 1.2 0.9-1.7 SomewhaU considerable 55 55 11.6 L 0-2.5 Sometimcs Soybean 70 72 1.5 1.0-2'.3 Rapeseed 87 63 2.0 1.3-3.0 Sometimes/' frequently None/slight 212 200 11.6 1.2-2.1 Frequently Soybean 59 56 1.4 0.9-2.3 SortxwhaV' 109 60 2.6 7 1 8-3 Rapeseed 90 30 2.8 1.".3 considerable . . Total Soybean 269 342 1.0 - ' Rapeseed 322 306 1.4 1.1-1.8 Ad)usted for afe. educnan and smo/nng . 'A4)uxod for age. aduratwn an:14molUna. TABLE.%I- RELATIVE RISKS.OF LUNG CA14CER IkSSOCIATED WITH NCMBER. OF DIFFERENT DISHES PER wEEK. PREPARED BY DIFFERENT NfT~HODS OF COOKING ~ `YmMtr .N d14heS' Per wee6. Caata Cnncrol,' RR' 9S4 Cl Srir fn-)ng 1~ 20 336 408 1.0 - 20-24 198' 211 1.2' 0.9-1.5 25-29' 48 47' 1.2' 0.8-1.9 ;~ 30 34 15 2.6 1.3-5.0 Deep fn•ing 0 502 594 1.0 - 1 85 68 1.5 1.0-2,1, 2 21 15 1.6 0.8-3.2 ;- 3 8 4 1.9 0.5-6.8 Boiling 43 96 124 1'.0 - 4-7 390 483 1.0 0.7-1.3 8-11 63 40 1.8 1.1-3'.0 .;Ir 12 67 33 2.2 1.3-3.7 ' Ad)y.ud ror aEe. educauon awd ~nokmR2 hai. Exposures to coal' or other fuel fumes were generally associated only with cooking, since nearly all homes in Shang- hai were unheated. Diet The women were asked about their usual' frequency of con- sumption ~ during adulthood of 32 commonly eaten foods, in- cluding the major contributors of vitamin A. Using Chinese food composition tables to estimate the retinol and carotene content of each food and applying these estimates to its fre- quency of intake, an index of'vitamin A consumption in m- inol~equivalent units was cotLstructed: The risks for lung cancer tended to be lower among those with low va]ues of this index TABLE VII - RELATIVE RISKS OF LUNG CANKER.ASSOCIATED w.7TH DIETARY INTAKE OF vITAMINA Vitammn, Quaruk k.el ofrnnsumpiion~ elPoSUR varuBlc I I H,Fh) 11 [I] 1% Viumin A 1.0 0.6 0.8 0:5 . index (0:5-0.9) (0.6-1.1,) (0.4-0.7) Retinol-rich 1.0 0.9 1.0 0.9 foods (0.7=1.3) (0.7-1.3) (0.7-1 ?) Caraene-rich 1.0 0.6 0:5 0:5 foods (0.5-0.8) (0.4-0.71 (0.3-0.61: 'Rulknelawve to h,gheslquartile.ofcoesurnp[son and d)usted for age. education atd smoiung. 95% CI in parentheses. (Table VII). This association was accounted' for mainly' by a lower risk among those with a reduced consumption of caro- tene-richfoods (the dominant source being dark green vegeta- bles). No effect on risk was found for consumption of the retinol-rich foods (mainly fisfi, eggs and Gver)i The patterns were generally similar for squamousJoat-cell cancer and ade- nocarcirloma, and for smokers and rton-smokers. Menstrual and reproductive fanors The risks of lung cancer were higher among women with ~ shorter menstrual cycle lengths (Table VIII).,T'he association, was primarily seen for adenocarcinoma. which showed a strong dose-response relationship. Among women.aged 55 years and' over with a natural menopause, the risk of adenocarcinoma tended to increase with the total number of inenstrual' cycles over their lifetime. Some increased risk of aderlocareinoma was seen when natural menopause occurred at age 50 or later (RR = 1.3, 95% CI = 0:9-1.7, after adjusting for menstrual cycle length). No associations were seemwith age at menarche. age at first pregnancy, or parity.

lkntilm oi mewrwl All cwleasen Ll!.NGCANCER IN~.CHINESE WOMEN~ TADLE 1.711 - RELATT'E R1SKS OF LUNG CAVCER ASSOCIATED W'rrH LE VGTH OF MEvSTRL.AL. CICLE. Cnrroks. RR' 9'SS Cl: spumw5 oa-ceil arrinoms >33 43 60 1.0 - 12 30-33 272 3271.6 1.0-2.6 62 26-29 241 268 1.6 1.0-2.7 51 <26 98 78 2.2 1.3-3.7 23 1.0 0.9 0.8 1.6 - 18 0.4-2 0 124 0.4-1.9 127 0.7-3 9 54 I.0 1,9 21! 2'9 - II.0-3.5 1 1-3_9 1.5-5 7 'Adjuued.fow aPe. e0ucauou. smotinF and reRutanny of inenuruanon. TAiLE IX - RF1aT1VE RISKS OF LUNGLAwCER FOR wOMEN,EVER.EMPLOYED IN MAIOR OCCUPATIONAL GROUPS. OccvRaan~.caterorn' Cases Controls~ RR~=~ 951 S CI 1-11 Professionals and technicians: leaders of 113 116 1.0' 0.7-1 4 UI-1V state organizatans, party and rnass, orga- nizations and enterprise units Office and related personnell sales workers 75 96 0!7' 0.5-1.0 V Service workers 1'39 160 1.0 0.8-1 4 Vl1 Agricultural. forestry, animal husbandry 24 21 1.1 0 6-2.1 VU-1X and fisher) workers Production.,.transportation and other 436 4711 1.1 0.9-1.4'. 0 related workers Never worked 61 75 1.11 0:7=1.6 'wbnoen empld+.ed In,monr than one occupalonal~.ntegonaRIncluded rntach aeeron in wAKh the% worked~ TAecoding uAeme wa, basedon.the s.uem usedin the l98:. Populairon Censw of the Peoplt's Rep+blic of China (Pop+linonCensus Office. 1985) ,-=Adjiuued for.aEer education and smoking Occuparrort . Most women reported working outside the home. but case/ control differences according to major occupational categories were small (Table IX). No major occupations were associated with increased risk ofl lung cancer. A decreased risk, however. was observed for women ever employed in the cotton textile industry. the largest employer of women in Shanghai. There was a slight increase in the relative risk of lung cancer among women ever employed as cooks (RR = 1.2. 95% CI = 0.6- 2. J). but few worked longer than,20 years. Family, history The cancer patients reported about the same frequency of lung cancer in their mothers (1.09E ) land fathers (1.7 %) as the controls (1.0% and 1.5%. respectively). The RR. adjusted for age. education and smoking, associated with having a parent with lung cancer was 1.1 (95 % Cl = 0:6-2.3). Mort: sibs were reported to have lung cancer, bur the numbers affected were small'(6 c:ses, 3 controls; RR = 3:0„ 9596 CI - 0.7- 12:5): Only one child, of a control, had' lung cancer., DISCUSSION The high incidertce of lung cancer among wornen in Shang- hai. together with the low prevalence of smoking in the general Population, led us to consider a number of possible etiologic factors. qlNk rigarlotte smoking was an important cause of ancer. showing a clear dose-response trend, the majonty Mg tumors, particularly adeno':arcinomas, occurred among non-smokers. Environmental tobacco smoke may account for some. but Probably few, of the cancers among non-smokers. since there w•as little or no association with' ever having lived with a smoker. Among non-smoking women married to smokers, however. there was an upward trend in risk associated with mcreasing years of exposure. This latter finding is consistent with reports in other parts of the world. When data from nearly a dozen studies evaluating passive smoking were com- bined (Blot and Fraumeni. 1986)., an overall 30`< excess of lung cancer (RR= 1.3. 95% C1 = l. l-1.5)was found among non-smoking women rnarried to smokers. with the RR reach- ing 1.7 among those most heavily, exposed'. Although the causal significance ofi the relation of prior, lung disease ro lung cancer remains to be clarified. the high preva- lence of previous pulmonary infections may have contributed in part to the high, incidence of lung cancer among Shanghai women. Earlier in this century. non-malignant lirng disease was one of the leading causes of death in China (Kan. 1981). With the advent of antibiotics and improved living conditions, the incidence and mortality of chronic litng diseases. patticu- larl) tuberculosis, declined. Nt:vertheless. a substantial por- tion (38%) of'the women with lung cancer in this study reported prior lung disease. including 12 % who were long-term survi- vors of tuberculosis. whereas signiffcantl'y lower percentages of controls reported these disaases.. To some extent it is possi- ble that recall or ascertainment bias may contribute to the associations observed~ with prior lung diseases. The elevated risk of lung cancer following tuberculosis. however. is consis- tent with recent studies in other countnesd and is not explained by cigarette smoking or treatment with isoniazid. a pulmonary prcinogen in laboratory animals (Howe er al.. 1979: Hinds rr al., 1982: Bakns e>' al., 1983); Emphysema was also significantly related to lung cancer. after adjustment for smoking habits- with the excess limited to squamous- and oat-cell carcinomas. This finding adds to the evidence that chronic obstructive pulmonary disease enhances the risk of lung cancer (Skillrud' er al.. 1986). even when controlling for smoking practices. Also rtotewortha is the ele- vated risk associated with, prior pneumonia. especially since an association with lung adenocarcinoma has previously been reported' among women in Los Angeles (Wu er, al:. 1985). While pneumonia typically occurred during adulthood in our study, the finding in Los Angeles pnmaril~ concerned child- hood infection. Little evidence was found to implicate the type of fuels used for cooking'in lung cancer risk. consistent with findingsfrom 607 RR' 951 CI 'b"- ~ RR' a4 Cl *0

608 GAO ET AL. Hong Kong (Koo ei aL„ 1983). The risks of lung cancer among Shanghai, women irtcrcased, however, with vartous measures of exposure to cooking oil vapors.,These included the number of different dishes prepared per week by either stir frying, deep frying, or boiling, the frequency of eye irritation when cooking: and the smokiness of the house when cooking. In Chinese wok cooking. regardless of the method tued, oil is usually poured into a wok and heated to high temperatures before meat or vegetables are added. Even boiling may entail' some exposure to cooking oil vapors. since oil is often added' to the water before heating Consequently. the living quarters may become smoky during cooking,, with opportuniry for exposure to intialable cooking oil vapors.. The plausibility off the hypothesis that lung cancer may be related to cooking oil vapors. particularly' from rapeseed oils used in Shanghat. i5,enhanced by , trrent.experimental investi- gations. In one study the mutagenlctt} ofipnoduets from cook- ing oil was assayed by the Ames test (Qu ct aL. 1986). The extracts of condensed~ volatiles of rapeseed oil, refined rape- seed oil, and soybean oil heated at about 270°C were all positive in tester strain TA98 activated with S9. The mutage- nicity of the extract from rapeseed oil' volatiles was stronger than that from soybean oil volatiles. There was no evidence of mutagenicity in the oils themselves, either, heated or unheated. In another study. the extracts of condensed'volatiles of rape- seed oil enhanced the yield of micronuclei' in polychromatic erythrocytes of'the bone marrow of'mice, with a clear dose- response relationship: reflecting damage of chromosomes and cell genocoxicity by rapesetd oil volatiles (Chen. 1987)( Al- though these tests often conelate with carcinogenic potential, no bioassay studies have yet been carried out, to our knowl- edge. if the effect of rapeseed oil smoke on lung cancer incidence is real. the problem is of great importance to popu- lations of eastern central China and other areas of the world where the oil is often used for cooking. Chinese rapeseed oil„ which is pressed from seeds of Brassica campcsrris, contains about 50% erucic acid (Chinese Academy of Medical Sci- ences. 1981). in contrast to rapeseed oil with <296 erucic acid (Canbra oil): which was Tecently approved for sale in the United States (Federal Register. 1985). Several studies have shown that the risk of lung cancer is elevated by a low intake of foods cotttaining vitamimA, partic- ularly as its precursor be'ta-carotene (Colditz et al., 1987). Although reported mainly in Western countries, this associa- tion has also been noted among Chinese women in Singapore (MacLennan cr al., 1977). However, we found no evidence of a protective effect among women in Shanghai. where iittake of fresh, carotene-rich, dark green vegetables is high by world standards. In fact. a positive association was observed between carotene intake and lung cancer risk in females (in contrast to no association in males). We have no ready explanation for this unusual finding in females. which was observed~ also in a case-control study of lung cancer in Hawaii (Hindscr a1:. 1984). However. the prntective effect of carotene-rich foods was mainly confined to current, smokers in one large-scale study (Ziegler cr al., 1986), and~ tHus the effect may be less evident in Shanghai ~ where few women smoke. A clue to hormonal factors was suggested by an association between menstrual cycle length and lung adenocarcinoma. A 3-fold difference in adenocarcinoma risk was found among. Shanghai women reporting short (<26 days)~compared to long (>33 days) menstrual cycles, with only' a weak trend for squamous- and oat-cell cancers. A relation of short menstrual cycles to breast cancer risk has been suggested in data from, Sweden (Olsson et al., 1983) and, to a Itrsser extent, the United States (Sherman er af., 1982)'. Some increases in lung ad'eno- carcitwma risk were also associated with late menopause an& with a high.estimated total number of menstrual cycli:s among women aged 55 and over having a natural menopause. A role of hormonal factors is also suggested by the observation, that among tton-smokers adertocarcinoma affecu proportionately tnore females than males (Lubin and Blot, 1984); and by the findings of'estrogen and progesterone receptors in some lung adenocarcinomas of women (Chaudhuri cr a1:, 1982). We discovered no relation to oral contraceptives or replacement estrogen therapy, but use of these compounds among women, in the study group was rare in Shanghai. I't seems unlikely that the menstrual patterns of Chinese women contribute greatly to their high lung cancer risk, but the internal consistency of the trends suggests that future studies of lung cancer in China and elsewhere should examine endocrine hypotheses in more detail. This large population-based case-control study of lung can- cer in urban Shanghai has confirmed that cigarette smoking is a strong risk factor among Chinese women., but only accounts for about one-fourth of all newly diagnosed cases. 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