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. - r • 6r. ! Caearr'(19901w 62. 982-987 tD Maaaitlan Press Ltdi. 1990 Lung cancer among rNomen iin north-east China A.H. Wu-Williams'; X.D. Dai', W: Bliut=. Z.Y. Xu', X.W. Sunfi, H.P. Xiab'; B.J. Stone. S'.F. Yu', Y.P. Feng', A.G. Ersttow=,,J. Sun', J'.F. Fraumeni Jr= & B.E. Henderson' 'Department of Preventive Medicine. (,lniversitn, oJSouthern CaliJ'ornia Schovl of Medicine. Los .{ngeles: Ca' 90t)33. 4!Sa: =National Cancer lnsritute; Bethesda, MD 2Q8D2. GLSa: 'Harbin Medical School: tYarbin.,FYeilongjiang Province. People*s Republic of China: and'Liooning, Public Health and Anti-Epidemic Station. Shenrang. Liaoning Province. Peop/cs Republic of China. S.auaary A case -control study of lung aancer involving interviews with %'5' female pa6ents and 959 controls in Shenyang and Harbin. two indtatrial cities which have among the highest rates of lung cancer in t?hina, revealed that cigarette smoking,u the main causal factor, and aooounted for about 35!y% of the tumours among women. Although tM amounCsmokad was low (threases averaged,ei.ght cigarettes per day)~ the peroentageof smokers among women over age 50 in these dties was nearly double the national average. Air pollution ftom eoal burning stoves was implicated, as risks of, lung cancer inereased'in proportion to years of exposure to 'Kang' and other heating devices indigenotu to the,region. In addition. the number of moalseooked,by deep frying and the frequeney of smokinaa during eookiag were asaociated!with risk of lung cancer. More cases than controls reported workplace exposures to ooal~dust and to smoke from burning fuel. Etevated,risks were observed for smelter workers and!decrcastd risks for textik workers. Prior chronic bronchitis.emphysenma. pneumonia. and'recentl tuberculosis contributed signi6antly to lung cancer risk, as did a history of tuber- culosis and lung cancer in family members: Higher intake of carotene.rich, vegetables was not protective against lung canr<er, in this population. The findings were qualitatively similar across the major cell types of' litng;canrcr, except that the associations with smoking and previous lung diseases were stronger for squamoust oat cell cancers than for adenocarcinoma of the lung. The rate of lung cancer among:Chinese females is among the highest in the world. Elevated! incidence, particularly of adenocarcinoma of the lltng, has beenl noted for Chinese females residing in different- geographic areas, including Singapore (Law et al., 1976);,Hong Kong (Kung et al., 1'984). Shanghaii (Gao ct aL, 1988)landl the United States (Hindk et al:,, 1'9811)j The high rates are unusual because, few Chinese women smoke tobacco. Within China, elevated rates of female litng cancer are foundi ini urban areas such as Shang- hail and in rural' as well, as urban, areas of the, northeastern provinces of' Liaoning and Heilongjiang (INational'. Cancer Control Office, 1980; Xu et al., 1986). Reasons for the geo- graphic variation and clustering,of high rates of lung cancer in the northerrt provinces are not known. We report here the results from case-control I studies conducted' in Shenyang and! Harbin; the two major industrial cities in Liaoning; and Heilonjiang provinces, to, evaluate the role of several poten- tiall risk factors. Methods In 1985-87;, investigators from the : Liaoning Province Public Health and Anti-Epidemic Station and l the US National Cancer Institute conducted a large lung cancer study includ- ing 1~51'7' males (729 cases. 788 controls) and! 1.073 females (518 cases; 555 controls). During the same time period, inves- tigators at, Harbin Medical College and the University of Southern California conducted a case-control study focused' on female lung,cancer(446 cases. 4013'controls). Investigators from bothistudies met during;the,planning phase of the study and adopted a unified protocol to ascertain and select cases and controlfr„ and a common questionnaire for the interview component of the study. Data on risks from smoking and air pollution among men and, women in Shenyang, have been published' elsewhere (Xu et aL, 1989)~ Herein we report risks among,females.associated with a variety of factors, increasing, sample sizes by nearly 80% by combining, information from the two cities. Correspondence: A.H. Wu-Williams. Received127 March 1990,•;and in revised form 25 July 1990. Case ascertainment; We sought to enrol all newly diagnosed primary lung cancers in females in the study areas between 1985 and I 1987: Utilis- ing;the cancer registries of Harbin and Sheny,ang; a system of rapid case ascertainment was established with the coopera- tion ofi all the major hospitals serving its area (about 3:5 in each city). In brief, the admitting physicians at' each parti- cipating hospital completed! a case abstract form whenever-a lung cancer was diagnosed. We recei ved these abstracts on al bi-weekly basis and selected as eligible cases those with primary; incident lung cancers diagnosed, among female resi- dents of the study area who were agedl less than 70 years at the time of diagnosis. The lung cancer diagnosis and cell-type classifiation were verified locally in each study area by a panel of pulmonary specialists and pathologists: Control,selection Controls were females randomly selected from the general populations of Harbinl and -Sheny;ang. Controls were fre- quently matched! by 5-year age, group too the expected distrif bution of! cases„ whieh was detetartined in, adivance using the number, andl age distribution of' female lung cancer cases reported in the two cities in 1983: A three-stage sampling procedure was used to, select,each control. The initial unit' for randomisation was the neighbourhood committee, of which there are about 1;500 each in Harbin and in Shenyang: Committees were randomly selected, with replacement after weighting,by their population sizes. Then we randbmly chose a household group from the approximately 10-25 household groups within each, selected neighbourhood committee. In the 8nal stage, among all': females in the 5-year age category within the household group, one was randomly selected! Questionnaire A structured„ pre-coded questionnaire was used by trained interviewers whoconducted personal interviews with the par- ticipants in their homesocwork sites or in,the,hospital/clinic. The interview gatheredl information on demographic factors, active and passive smoke exposure, lifetime residential and occupational histories, diet and, cooking practices; personal history of nonmalignant lung diseases; history of tuberculosis t

~,. s~~- .~~tv LUNG CANCER AMONG WOMEN IN CHINA 9E3 (TB) and cancer in first degree rdatives. and reproduaive fac'tors. Questions on smoking included' the amount andl types of tobacco products smoked, age when smokin? start- ed, and for ex-smokers, age when smoking stoppedi To assess passive smoke exposure,, we asked about lifetime resi- dential exposure to tobacco smoke from cohabitants; includ- ing the amount andiduration of exposure from each smoking cohabitant. In addition, we asked if the subject was exposed to passive smoking at each work place. For each residence in which a subject lived for three or more years. we askedJ in detail about heating and cooking practices: including methods for heating and cooking and types of fuels used: Several questions wertasked about 'Kang'.. brick beds com- monly used l in the north-eastern part of China, which are heated either directly by a stove underneath them or by pipes connected' to the cooking stove. To assess dietary habits 5 years prior to interview, we asked subjects to estimate their frequencies of intake of 33 foodlitems, including staple grains (dice, wheat; mai¢e), soya bean products (bean curd. fbrment- ed bean paste), dried peas and beans, animal I protein sources (eggs, fuh. shellfish„ liver, poultry„ pork): fermented/salted foods, alcoholic beverages, and fresh vegetables and, fruits. Also inclhded I were questions on diagnosis by a physician of ' previous each lung diseases, age at lung disease diagnosis, and, ifihospitalisation was required. Information on outcome of each pregnancy, age at menarche and' at menopause was 'so elicited. As a quality-control measure: interviews were .assette-recorded for review by a field supervison. Statistical methods The data were edited: coded, keypunched and submitted too computerised range and consisteney, cheeks. The statisticaL' analyses were based on multivariate techniques for case- control data (Breslow & Day. 1980): Unconditional logistic regression analyses were used to estimate summary relative risks (RRs) of lung cancer associated with various factors while adjusting for other factor& RRs were calculated for all lung cancer combinedi and for specific cell I types. We present results for squamous cell and oat/small cell cancers combined because we had too few oat/small cell cancers to conduct separate analysis and because these two cell types of' lung, cancer are more strongly associated with smoking than adenocarcinoma of the lung (Lubin & Blot, 1984). Our analysis for adenocarcinoma,of the lung did not:include large, cell cancers. There were too few large cell cancers (br in- clusion by cell type. ln the analyses including all subjects, thee regression models contained terms for age (less than 50,, 0-59; 60-69 years), education (no formal editcation: pri- ry or secondary school, high school and'higher); smoking (non-smoker. smoked 1-19 cigarettes, per day and 11-29 years. 1-19 cigarettes per day and 30-39 years, l 19 cigarettes per day and 40 + years;, 20 + cigarettes per day and 1-29 years„ 20 + cigarettes per day and 30-39 years. 204 cigarettes per day and i 40 + years) and study centre (H'arbin versus Shenyang). We also conducted analyses restricted to nonsmokers: deleting the smoking variables in the regression model and adjusting only on age. education: and centre. Results (n = 3110) 1 adenoctrcin omas. 28% (a -i 20111 squamous cell carcinomas. 16% (n= 117) oatPsmall!cell carcinomas and the remainder were large cell ctrcinomas, mixtures of other eelll types or the cell type was not known (n = 66)j A total of 959 controls (404 in Harbin. 555 in Shenyang) were interviewed. Cases (mean age 55.9 years) and controls (mean age 55.4 years) were closely matched on age bur, wses were less educrted than controls. Relative to those with no formall education, the RRs for women with primary.juniory school, high schoolltechnical school or college education was 0:9; I10. 0:8' respectively (RR for linear trend' 0.9: 95% CI 0:8-1.0): Smoking habits Table I shows the percentages of'women by 5-yeara¢egroup who smoked cigarettes for 6 months or IonKer. The preval- ence of smoking in, the general population (i.e. among eon- trolt) varied with age. being much higher (approximately 40%) among women 50 or over than among women below 50 (smoking rate 24%.), but increased risks were seen in smokers at all ages. For all litngcancers eombitted. smokers experiencedl a 2.3-fold (95% CI 1.9-2.8) increased risk of lung cancer. The age-, education- and city-adjusted RRs for smoking were 4.2 (95% Cl 3.0-5.9) for squamous cell cancer. 2.2 (95% Cl l_4!-3.2) for oat/small cell cancers. 1.5 (95% Cl 1.1-1.9) for adenocarcinoma of the litng and 2.5 (95%.' Cl 1.9-3.3) for the 'other` category which included those diagnosediclinically, large cell eancers, and those with mixed or unknown cell I type. Most (57 ;'o) cases began smok- ing before they were 20 years old: compared to 40% of' controls: the average age when subjects began to smoke was 1'919 for cases and 24.0 for controls. The womeni were not heavy smokers. Few subjects (9%% cases. 4°>% controls)') smoked 20 or more cigarettes per day,: and the mean daily number of cigarettes smoked was 8.1 for cases and 6.8 for controls. Neverthelessi there was sufficient variation, in amounts smoked to show that risks oC lung cancer signi- ficantly (J'<0:001) increased' with increasing numbers of cigarettes smoked per day and with increasing duration of smoking (Table II). Clear independent effects were seen with each measure of'smoking exposure within categories of the other. with the associations stronger for squamous;oat cell carcinomas than for adenocarcinoma. At the same level of smoking, 2- to 4-fold differences ini the magnitude of the risk between the two cell types were typicalliy observed, Passive sn+oking, Table Il: shows the RRs associated with passive smoke exposure, first among all subjects after adjusting for personal smoking and then among non-smokers. Eighty-eight per cent of all''cases and controls reported having lived in at least one of their residences with a cohabitant who was a, smoker. There were no significant case-control differences in ever having livedl with a smoker, except for non-smokers who lived with,a spouse who smoked, where the risk was reduced with (RR 0.7; 95% C1 0.6'-0:9): The lowered risk associatedh a spouse who smoked was seen, only in Harbin: 60% of non+smoking controls andl 46% of non-smoking cases in Harbin reported that the spouse ever smoked; compared to 52% of non-smoking controls and 52% of non-smoking All interviews were conducted in 1'985'-87: At the close of case recruitment„ 1,049 eligible patients hadl been identified by the Harbin andlShenyang cancer registries. Nine-hundred and sixty-four (91.8%) were interviewed, 32 (3,.1 %) died before our attempted contact, 50 (4.8'%), were not located and three (0.3%) refused to participate. Forty.two per cent (n = 405) of the, cases were diagnosed by tissue biopsy, 32%, (n = 309) by cytology, and 26% (n = 351) by radiology. Although the percentages of patholog- ically and cytologically confirmed cases were higher in Shenyang, than, in Harbin, the cell-type distributions were similar. In the combined set of cases, there were 44% Table I: Prevalcnce of smoking by 5-year age groups and correspon- ding,relitive risks for lung cancer associated with smoking Cases Conrriols. e % Age (Ye+ars) n smokers n smokers RR (95% C1) , <:50 200 34 163 24 1.6' (1.0, 2.6) 50-54 203 60 1% 35' 2.7 (1.8, 8.0) 55-59 232 62 241 43 2.0 (1l.4, 3.0) 60-64 184 68 191 39 3.2' (2.115.0) 65 + 1;37 60 1161 40 2:2' (1A, 3:5)

: .984 ~ A:H. WU-WILLIy11MS'et aL TabYe II RR and 95% Cl for lung canoer associated with inteosity of strwking by ao(l type Du.ation ol snwlc'ing (yearsl. CigRrttrts Cell rrpe per day jo-19 >40 All lung cancer 1-19 1.3 (1.0. 1;7)' (1118/125Y' 2:6 (I1.9. 3:5)', (146/83) 3.2 (_.4.1.3) Q187/103Y >, 20 1.8'(0:9;,3:6)', (i19144) 3:3(1.8;,6.2), (33115) 5.7 (2.9. ('dl5) (36(QI). Squamous/oat cell 1-19: 2.0 (1.3. 2.9) (48/125) 1 3.9 (::6; 5:9)~ (56/83) 4;7'(3' 1. 7:II) i(64/103), >_ 20 '-.0 (0.7; 5.4) (6/14) 3.8 (1.7, 8.8)1 (1I0/('S) 12:0 (5.3, _7.0) (17/11)', Adenocarcinoma 1-19 0.8I(0.5: 1.3) (30/125) 1.7 (1.1. 2.5), (37/83) 2.0 0.3. 3.0) (45/103) _> 20 0:8'(0J: 2.6) (4/14) 3.8 ((.8.8.0) (1'5VI'5) 2.8 (1.0. 7.4) (7/I I') '95% confidence intervais.'Numbers of pses/eontrols are in parenthesa.. Table III RR, for lung cancer associated with, passive smoke Table IN' Relative risk of lung cancer associated with years of use of exposure specific heating devices .aV!'n•bjects Mon-satokersonlr Sower of parsiwr satoke erposure' Pauirn smoke exposure Casa/ controls RR' Cau/ eoarrrols RR6 ' Any cohabitant' no IJ2r1III', 74/87 ves 844Y842 0.8' 343.151,15 0.7 Spouse no 398/402 212/27( yes 5581551 0:9' 205/331 0.7 Mother no 543f595' 29g/410 yes 413%358 1.0 1119/192 0.9 F 'her no 484/515 235/352 yes 472,1438 LO 18E/250 1.1, ~. ., kplatce no 4031448 187/301 yes 563151'3 1.2 2281301'! 1.1 .'Adjusted for age, eduation, personal smoking and', study area. "Adjusted for age, education, and study area. `P<0105. cases in! Shenyang. There were no significant trends in risk with intensity (i.e: number of' cigarettes smoked by family membersYand duration of exposure~(i.e. years of smoking by cohabitants)„ except far an increasing risk associated with increasing intensity of, father's smoking in the presence of'the index subject. There was a small excess risk associated with passive smoke exposure at' the workplace. For alll subjects, the smoking-adjusted RR was 1.2 (95p/. CI 1.0-1'.4)i The resultt was similar, for non+smokers (RR 1.1; 95"l. CI' 0,9-1.6). There were' no significant dose-response trends associated with years of passive smoke exposure at work. Heating and cooking, practices. T-hle IV presents RRs associated' with duration of use of ; and other heating devitxst Elevated risks were observed fo. -,tcreasing years of use of Kang (particularly when heated by stoves underneath), heated brick w,alls or floors (i!e. heated by pipes leading from the stowes to the wall or ftoor),, coal stoves and coal': burners. On the other handl decreased risks were observed for, increasing years of use of non.coal- burning,stoves and central heating. The patterns were generr ally simihr for smokers and non•smokers, and'for squamousj oau cell'txrcinomas and adenocarcinoma. Wk also examined the risks associated!with years when coal, wood„andlcentral heating served as the main fuel i for heating. Tlhe R'Rs tended to rise with increasing use of coal and decline with increasing use of wood l and central heating, but none of, the trends was significant. Cases more often reported that their homes became smoky during, cooking and that they more frequently had I irritated eyes during cooking (Table V). There also was a significant trend in risk with increasing number of meals cooked by decp fuying, although this method of cooking was : not fre- quently used. The results were similar for squamous/oat cell cancers and adenocarcinotna, and for smokers and non- smokers. Occtrparlott SubjaCts !rere t•shad about all jobs in which they had i worked `~ ,Or A1~ef: yet•ti. W ,eau:a and conta+ola comp.red in terms j Earpaswt,(}zorsl Catt,;controls RR't9'3•/, CI) Kang 0 25/40 1.0. 1-39 384076 1.4 (0,8. ? 4) , 40-49 132/i144 1. 1 (0i6, 2.8) 50 + 4'15/393 1.6 (0.9. ?8) Burning Kangs 01 677/740 Il0 t-20 106t91 1?'(0:9: 1.7) 21 + 173/122 1.5 (t.l, 2:0) Coal stoves 0-20. 192/226 I L0 2!I -40 51fi/485 1.2'('(L0: (:6) 41 + 253/242 1.3' (110. 1.7) Non-coal stoves 0 2121183 ' 1.0 1-20, 367/340 0;8 (0.6: 1.1) 21-30 259/295 0:7 (0:54 0'9) 31 + 118/d35' 0.8 (0:5;,1.1'), Heated brick walls/Boors 0 5861651 1.0 1-20 127/98 1.5'(1.I. 2.11 21+ 243/.'.04 1.4 (1.1. 1.9) Coal burners 0 525/583 1.0 1-20 258/202 1.2 (1.0, Il6) 211+ 173/16'8 1.1 (0.8. 114) Central heat 0 602J573 I LO 1-20 21S'/200 1.0:(0.8; 1!3) 21 + 139/180 0:8'(0.6; 1:0) •Adjusted:for age, education, pctsonal'lsmoking and study area. Tabl! V Relative risk oflungcancenassociated!with frequentyofdeep frying,and eye irritation,when cooking Casts/corttrols RR' ('9S"J: CIJ' Deep fry (times per month) 0 : 324/403 1.0: 1 326/360 I.2 (1.0. 1.5) 2 170/107 2.110.5,2.8) 3+ I21/81 119:(1.4, 2.7) Eye irritation never/rarely 647/732 1.0 sometimes 218/163 116'(1.2, 1.8) frequent 89/56 1',8'((.3, 2.6) •Adjusted'for age, education, personal smoking and,study area. of their employment in 29 job categories: Most (77%) women held at least' one job outside the home, but signi- ficantly increased risks were observed only for metal smelting work (RR 1.5; 95% CI 1.0-2:1'), while a, significantly decreased risk was observed for textile workers (IRR 0.6; 95'/0. CI 0:3'-1.0). The women were also asl.edl if' they were exposed to 12 specific dusts,, smoke or fumes at work, with from li to 16% reporting on-the-job exposures to the 12', pollution items. Cases reported exposure to coal dust (IRR 1.5; 95% CI 1.1-2.0) and to smoke from burning fuel (RR 1.6; 95'/. CI 1,2=2:2) significantly more often.

. <.-n~ ~ rr~treettsax~ . , ~~101, , ~ LLDNG'CA'NCER AMONG WOMEN IN CHINYA 983' Prior lung disease Table VI' lists R'Rs of lung cancer associated with specific prior chronic lung diseases. Lung diseases that were first diagnosed' within three years of lung cancer diagnosis (and a comparable time period i for eontrols) were excluded from the analysis. After adjusting for smoking, history of any prior lung disease was associated with a, 50%% increased risk (95% CI 1.2-1L8): The excess was greatest for pneumonia, (RR 2.1). An, increasedi risk was found for bronchitis and/or emphysema, but the association was limited I to squamous/oat cell cancers (RR IL6) and'not found for adenocartfinoma (RR 0.9). We inv,estigated whether risk of lung cancer varied accord- ing to the lag ame following the diagnosis of prior lung disease. Earlier detection of'chronic bronchitis/emphysema eonveysd' greater risk. Relative to those with no history of chronic bronchitis/emphysema; the RRs arere 113. 1.3: and 1.7 respectively for conditions detected 4- b0. 111-20. and 2'1 + years before lung cancer diagnosis. On the other hand, the RRs were higher for'more recent diagnoses of pneumonia and TB. The RRs were 2.7, 2.5' and 1.8' respectively' for pnetunonial and 2.8. 1.1, and 1.2 for TB fust detected 4-10. 11-20 and 2!1I+ years prior to lung cancer diagnosis. The elevated risk associated with TB diagnosed 4-10 years prior, lung cancer was significant; it was observed for both .iamous/oat cell cancers and adenocarciaottta of the lung, and among non-smokers as well as smokers. Tabk VIl Relativesisks of lung caneerassociated with menstrual and: reproductive factors Casesiconrrols RYit ':95'•, CIJ Age,at menarche 18 + 184r19'_ 1L0 16-17 427.'41C 1.1 (0;8: 1.11'. 14-15 =85i276' 1.103. 1.41 <l4 5544 U19'(0i6: 1.41, Number of children <3 P93i_05' L0' 3-4 319,300 1.1 10:9. 1.51 5-6 275:27i' 1.0(0:8. 1.4) 7+ 1691,174 I.Ot0:7.1.31 Age at natural menopause <45 77J1_' 1.01 45-49 373Y303 1.7 (1.2.2.41 50-54 278627 ' 1.3 (0.9, 1.81 55+ 31;28' 1.7(1.0.3.21 Positive history of Hysterectomy 36136 1.00.6. 1!6) Miscarriage 8,2.'136 I18) Spontl abortion 239/218 1.1 I(0.9. 114) Difficult labour 76i6l 1.3 (0.9. 1 m Oral contraceptive 54/68 0.8 (0.5. 1:2) 'Adjusted,for age. education, personal smoking and study area. Fomily hirtory of TB and cancer We observedl a significant 60% (95% Cl' 1.2-2.1) increasedl risk associated withi TB'in!a household memi with similar risks for squamous/oat cell cancers and adenocarcinoma. The familial association was seen in, smokers and non- smokets; and remained unchanged after adjusting, for personal history of TB. The risk associated with family his- tory of TB increased with decreasing age when the index subject was first exposed. After adjusting for smoking;, exposures ar age <211, 21-30 and >30 conferred risks of 1.7. 1.5 and i 1.2' when compared to those with no household I TB exposure: Family history of lung, cancer in first degree relatnves„ reported by 4.5% of the cases, was associated with a signi- ficant 80% (95% Cl 1.1-3.0) increased risk. There was little difference in risk by cell type or smoking status. The risk of lung cancer was somewhat higheramong,those with a family `~story, of other cancers (RR 1.4;:95%. CI 1.0-2.0). with the. ss risk being, higher for adenocarcinoma (R'R' 1L8) than, tur squamous/oat cell cancers (R'R 1.1). Menstrual'and reproductia•e factors Table: VII presents risks of lung cancer by various menstrual and reproductive factors, There were li'ttle,or no association with age at mcnarche, parity, hysterectomy, spontaneous abortion, pregnancy resulting in difficult, labour; and use of oral' contraceptives. There was a significant 50'/. (95'J. Cl 1.2-1.8J' increased risk associated with history of miscarriage. and cases tended to ha ve a later age at natural menopause although the trend was not smooth. Dietan• factors' The diet' of' the subjects was dominated' by staple grains (median intakeamong,controls= 1.095 times per vear),Iresh, vegetables (1.188 times per year). fermented salted foods (7300 times per year)1 and soya bean products (365 times pen year). Less frequent was consumption of' animal protein sounces. (231 times per yearL fresh fruits (52 times per year). and peas and beans (12 times per year). Risks of lung cancer in relation to dietary intake are shown in Table VIiL Higher frequencies of intake of vegetables, either those rich or low in carotene content were nor significantly protective against lung cancer. The three foods with the highest carotene con- tenc in this study population were driedl hot red peppers (Ii6A mg of carotene per 100 g); dank:le•afy greens (-'•7 mg of carotene per l00 g), and carrots (2.0 mg of carotene per 100 g). Carrots and dried hot red peppers were consumed, less often by cases compared to controls„but these items were not frequently consumed (mean intake among controls was 411.4 and 70.0 times per year respectively). On the other hand, cases had slightly higher intakes of the more commonly consumed dark leafy greens (average intake among controls was 163'.5 times per year). Cases reported higher frequencies of intake of animal pro« tein and fresh fruits. Few women (12% cases versus 8°/% controls), drank alcohol more than once a, year. but they showed a significant smokingadjusted!304/. increased risk of lung cancer compared to those who did not drink at' all. However; there was no clear trend with increasing alcohol consumption. There were no appreciable differences, in die- tary patterns for squamous/oat cell cancers versusadenocar cinoma. nor for smokers versus non-smokers: Tab'k VI Relative risk for lung cancer associated with previous lung diseases All lung Squamonsloar Adenocarcinoma Casesl, controls RR• (95Y.' Cl). .V' RR* N' RR' Positive history of: chronic bronchitis 210/137 1.4 (l17;,1.8) 79 I.ff ' 46 0.9 and/or emphysema pneumonia 66/28 2.1 (I:3: 3.3) 23 2.3" 15 1.6 tuberculosis 103)83 1.3 (0:9: 1.7) 33 1.2' 33 1.1 'Adjusted for,agq, education, personal'smoking andstudy area. 'Number of cases with, factor. `95'/% confidence intervals excludes 1.0.

t - : .9e6 ' ~ )1.H. WU-WILUrAMS et aL' Tatik VIU Relative risk of' lung canoer associated with dietary faetors Dietarp factor lerakr trimes per rear) Caxlconrrol RR' (95% C!). Staple grain < 1095 3081266 1.0 1095-1L46' 352.~396, 0:8(0.7; l.1) > 1146 ':901290 0:9 (0.Z: 1.2), Peas and beans <i 256/241 1.0' 4- I S' 221/244 0.9 (0.7. 1.2) l b-52 3191314 t.1' (0.8. 1.4) > 52 1ti0L152' 1!0 (0:7, 1:3). Soya bean products <153 232/'!.'17' 1.0 153-365 ?041266 0:7'(0.5: ,0:9), 366-485 265l23'0 0J9 (0:7. 1.2), > 485' 255)Y19 1.0 (O.B. 1.3), Animal protein < 109, 156('tJ8 1.0 109-230 229r-36 1.6't1:2.' 2.1) 23l -447 235(237' 1:6(112.2.t) >442 336)241 T.34I1.T 10) Fermented/salted <:36'6 23ir273 1.0 foods 366-625' 179/154 1.2 (0!9, 1.6) 626-990 329/306 1.2 (0.9, 1.5) > 990 214/219: 0.9 (0.7.1.2) Vegetables' low in <366 254,i25i1 1.0 carotene content 366-547 2567251 1:0 (0.8i 1.3) 548-730 248/240' 1.01(0:8J 1.3)) y 7311 l9(i/Zl0 01 (0i6:,t.1:). ~ •ables high in <731 20t12'L3 1.0 a..,,ene content 731-1095 355/331 L.l (0.9, 1.4) I 096-1460 195/ 197 1.00.8. 13) y 146 1 20501 0.9 (0.7; 1.2) Fresh fruits < 19 2031232 ' 1.0 19 ~ 52 209/:+t9' 1.0'(0:8. 1.3) . 53-132 256r231 1.4{1.0; 1.8)' >932' ?88.1Y40 LS (1.2. 2.0), AIcohol'beverages 0 649/706 1.0, l 1-12 110/96 1.3 (0.9. 1.7) 13-52 81/76 1i0 (0.7: 1:5) > 52 116175 1:3'(11o: 1.8) 'Adjusted for age; education, personal smoking andlstudy area.. °Includes white potato: pale sweet potato, whitevegetabks yellow and green,gourds. 'Includes saltedlvegetables: dark sweet'potato; yellow green squash, dark green leafy, greens, yellow and light green leafy vegetables, carrots, red peppers, dried hot red peppers, green peas, tomatoes. Muhlvarrate analysis The factors found to have a significant effect~ on risk of lung cancers in univariate analysis were evaluated simultaneously in multivariate unconditional logistic regression analysis. In a, !on to smoking, the followingvariabtes had a1 significant effi in risk of lung.cancer (P'<D!05) and they entered'the regression model in the order as shown: deep-frying, eye irritation, pneumonia, household tuberculosis, burning Kang,. ;clC reported'. oecupational'. exposure to burning fuel, passive >moking from any household member andlheated'brit:k wally joon. ~iscttssioa -his population-based case-control study conducted in twor arge northern Chinese cities revealed that at least 35°/% of the ung cancers among, women can be explained by cigarette moking. Although this attributable risk is low compared to :aucasian female populations (Lubin & Blot„ 1984); it is igher than elsewhere in China (Chaner af:,,1!979;,Gao er al:, 988), mainly because of a higher, prevalence of smoking ,omen in this regiom Smoking rates among women over age 0'were nearlydouble those found in Shanghai or ttakionallyy vChina (Gao et'al:, 1988; Weng et al.,, 1987). Furthermore, •omen in Harbin and Shenyang startedl to smoke at a :latively, young age. As compared to women ini Shanghai; here 19'X% of female smokers in the general population :gan smoking, at, age 19 or youngcr, approximately 40% arted at this age in, northern China. Hence, even though nmtutts smoked were low (averaging eight cigarettes per day i 7ti '~~. a'lTay. among the cases), smoking contributes to the eleHated rates of lung cancer among northern Chinese women. It also appears to account for the higher percentage (•btY.) of squamous)oat'cell cancerrin our studyversus:32!'y and 3'5%., respectively, in Shanghai.and Hong Kong (Gao et aL, 1988; Kung et al.. 1984): The relatively low mean daily number of' cigarettes smoked by these women may explain the lower relative risks of lung cancer among, Chinese compared to Caucasian smokers. We observed, no overall associatipni between lung cancer risk and passive smoking. Our results varied by source of passive smoke exposure. however. with nonsmoking cases reporting less exposure fromi spouses (but only in. Harbin). more exposure from i fathors, and I similar exposure from i mothers when compared to non-smoking' controls. Despite. the large size of our, study, we were unable to clarify the magnitude of risks due to passive smoking, tticol as a cause of lung cancer around the world (Surgeon General. 1986). Perhaps in this study population the ettects of environ- mental tobacco smoke was obscured by the rather heavy exposures to pollutants from coal•butning Kang; other indoor heating sources, and high levels'of'neighbotuhood air pollution (Xulet al.. 1989): Pollution from, coal' burning seems likely to contribute to north-eastern China's elevated, lung, cancer rates. Risks in- creased with increasing years of use of' burning Kang and heated brick walls/t)oors. and we observed weaker but similar trends with use of coal stoves and coal'burrters. Levels of'air pollution have been reported to be high in both Harbin and Shenyang; with both indoor and outdoor wintertime bettzo- py,rene concentrations exceeding standards ftar cities in the United States by' more than 60-fold (Dai' er al: personal communicationi Xuiet aL. 1989). Coal burning, especially use of a locall smoky coal, has also been implicated in, the high lung cancer rates reported among women in Xuan Wei County in southern China (Mumford er al.. 1987). The effects of certain workplace exposures on,lung cancer resemble those reportedl in Shanghai (Levin et at:, 1987. 1988), including, a decreased risk seen in textile workers. The excess risk among women employed in metal smelting is consistent with the three-foldi increased risk among men exposed'to inorganic arsenic in,copper smelting in Shenyang (Xu et al:, 1989) and the United, States (ILubin et al.. 1'981). The oocupationall findings will be presented in more detail in a separate report. Our findings that, cases' were more likely to cook food l by deep frying and to more frequently report eycirttitation whenl they cooked are consistent with the increased risks associated with exposure to cooking oil fumes in Shanghai (Gao et al.. 1987). The association in Shanghai was strongest for use of rapeseed cooking oil, but few women in Harbin or Sheny,ang, used this type of', oili suggesting', that vapors from several types of cooking oils may be linked to increased risk. Con- densates of both rapeseed and soya bean cooking oil'volatilesl have been found to be mutagenic (Qu et al.. 1986). Further' short-term testing of several types', of'cooking oils is under- way to help identify the responsible constituents and provide leads for additional l study. Certain lung diseases may, have an aetiologic role in lung caneer, development (Gao et al.. 1987; Wwrr al., 1988). Suchh an association is of particular importance in China, where the prevalence of chronic lung disease, is highi Indeed we foundlthat 35% of the cases and 24% of the controls report- ed prior chronic lung disease. Like others,, we found an cxecss', risk of squamous/oat cell cancers of the lung, but not, aden'ocarcinoma, in association with chronic bronchitis/ emphysema. Our finding of a significant increasedl riskk associated with recent diagnosis of TB (i.e. 4- 10 years prior to Iung, cancer) is consistent with results from Shanghai (Zheng et al.'„ 1988): Our results are supportive of' a! familial tendency in lung cancers (Cohen et a1.'„ 1977; Ooi et al:, 1986a,b; Skillrud et al., 1987; Wu et al:. L'9.88). Shared environmental exposures„ familial aggregation of smoking habits, and/or genetic predis- position may' Ue important. The percentage of cases having',

LUNG CANCER AMONG WOMEN IN CHINA 9877 atfixted' first-degree family tttembers was small (4'/.). Recent case-control studies in Great Britain (Ayesh r/ al.', 1984)and the United States (Caporaso et al„ 1989); however. suggest that' genetic trrits may influence susceptibility in a sizeable portion of cases. These investigations revealed significantly increased risks of lung, cancer associated with the genetically controlled I ability to extensively metabolise the drug dcbriso- quine, a trait affecting,54"C. of the control population studied ini the United States:. We found no strong support for a role of hormonal factors for lung, cancer overalli or specifically for adenocarcinoma: The cases did tendlto experience menopause at later ages; but the trend in risk with age at menopause was not smooth. History of prolonged labour or hysterectomy; which had been suspectedlas risk factors for adenocareinoma because of the potential for trauma-associated lung embolism, occutredl more frequently among our cases, but the excess risks were not>signi6cant since relatively few women were affected. Risk of lung cancer was recently reported to be increased among Chinese women with short menstrual cycle kngth (Gao let aC, 1988); but this variable was not assessed irrthe currentstudy,: In other countries the risk of' lung cancer is generally reduced among, those with higher dietary intake of' carotenoids (Ziegler, 1989), but our findings are less clear. Cases had slightly higher rather than lower intake of dark green leafy vegetables, the mosn commonly consumed rich -)urce of carotene. Moreover, in our analysis using a corrt- .,ined index of all vegetablbs richl in carotene, high frequen- References AYiFSH, R:,,IDLE;,1.. RI1fCH1E. 1C., CROTHERS. MJ. & HETZEL.,M:R'. (1984). Metabolic oxidation phenotypes as markers for suscep- tibility to lung cancer. Nature. 312, 169: BRESLOW. N.E. & DAY. N.E. (11980): Statistical Methods in Cancer Resemob: thr Analysis of Case-Control' Studies. IARC: Lyon. CAPORASO. N.E., FALK. R.T..,ISSAQ; HJ. & 5'others ('1989): Lung cancer risk, occupational exposure. debrisoquine metabolic phenotype. Cancer Rts:,,49, 3675. CHAN. W,C.. COLBUORNE. MJ!. FUNG: S.C. & HO. H:C. (1979);, Bronchial cancer in Hong, Kong 1976-1977: Br, J. Cancer. 39, 182. COHEN. BJ.. DIAMOND. E;L_ GRAVES. C.G. & 6 others (1977). A common familial eomponentl in lung,eancer, and chronic obstruc- tive pulmonary disease. Lancet, iil, 523. ERSHOW, A.G. & CHEN. W.K. (II990)j Chinese food composition tables: a translationwith,English eommon names. Latin scientific names, and Pinyin romanized transliterations: Food'Comp. Anal. (in the press). '=AO, Y:T.. BLOT, W:L, ZHENG. w: & 5 others (1987), Lung cancer among Chinese women. lnr. J. Cancer, 40. 60r<:. GAO. Y.T.. BLOT. W:1.. ZHENG. W.. FRAUMENI. J.F. & HSU. C.'W: (1988). Lung,eancer and'smoking,inShanghai. Int: J. EpitJemiol, 17„ 277, HINDS. M.W:, STEMMERMANN. G;N.. YANG. H.Y. & 3'others (11981)j Differences im lung, rancer, from, smoking among Japanese. Chinese and'Hawaiaan women in Hawaii. Inr:J: Cancer. 27. 297. KWNG, t., SO, K. & LAM. T. (1984). Lung canoer in Hong, Kong, Chinese: mortality and'histologic types 1973-1982. Br. J. Cancer. 90; 381 i 1:AW, C.H.. DAY. N.E. & SHiVNMUGARATNAM. K. (1976). Incidcttce, rates of specific histological l types of lung eancor, in Singapore, Chinese dialect groupr. and their actiological significance. Int. J: Cancer, 17„ 304. LUBIN. 1:H. & BLOT~ Wi. (P98!4). Assessment of lung, cancer riskk factors by histologic category. J. Norl Cancer lnst.,, 73, 383. MUMFORD, J.L., HE, X:Z:. CHAPMAN. R.S_ & 9 others (1987). Lung cancer and indoor air pollution in Xuan, Wei. China. Scicncq. 235, 217. cies of intake did not confer a significant protective effect. Reasons for the absence of protective effects are not clear. A possible explanation is that three-fourths of the study population, ate vegetables high in carotene content at least twice ay day so that the nearly uniformly high i intake of carotene-containing, foods limited variability and hindered, detection of an effect. IData on plasma carotene levels from this study population will l be important as a more objective measure of their dietary intake. Misclassification ol' intake also may have dampened trends. We did' not have inform- ation on portion size and the highest carotene-containing food in this population is dried hot red!peppers, usually used as a condiment. In •rddition: recall of past diet mav have been influenced by recent dietary improvements, perhaps more so among cases who may have been given preferential dietary treatment because of their illness. In summary,: this investigation reveakdl that contrary to a priori expectatietn, in China, cigarette smoking is the major cause of lung cancer among women in north-east China and contributes to the area's high rates of' mortality from this tumor. Prevention activities should emphasise smoking cessa- tion, while additional study may help clarify the role of indoor and outdoor air pollution, chronic non-malignantt lung disease; occupational exposures, familial susceptibility and other factors in the aetiolbgy of lung cancer. Wo thank Joan Howland for preparation of' the manuscript. NATIONAL CA'NCER' CONTROL OFFICE (1980Y Nanjing Institute of Geography Atlns of Cancer Aforralitt^ in the Pcopft,'s Republic of China. China Map Press: Beijing: OOI. W:L.., ELSTON. R'.C.. CHEN. V:W,, BAILEY+WIIL9ON; 1.E & ROTHSCHILD, H. (1986). Increased familial risk for lung,cutcer. J. Ncr! Cancer lnst:,, 76, 2!17: 001. W:L.. ELSTON. R'.C.. CHEN. V,W,, BAILEY-wI[SON: I.E. & ROTHSCHILD. H. (1986). 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