Tobacco Documents Online

Smoking and Other Risk Factors for Lung Cancer In Women ''z Anna H. Wu, Ph.D., 3 Brian E. Handtrson, M.D., 3 Malcolm C. Pike, Ph.D:, 3.' and Mimi C. Yu, Ph.D. 3' ABSTRACT-A case-control study among white women in Los Angeles County was conductisd to investiyate the rote of smoking and other factors in the etiology of lung cancer in women. A total lof 149 patients with adenocarcinoma (ADC) and 71 patients with satumous c.U carcinoma (SCC) of the lung and their al and sex-matched controls were interviewed. Personal ciparena smoking accounted for almost all of SCC and abouthalf of ADC in tha study population. Among nonsmokers, slightly elevated relative risk(s) (RR) for ADC were observed for passive smoke exposure from spouse(s) (RR=1.2; 45% ' confidence interval (CI)=0.5, 3.3Jiand at work (RR=1.3;,95% C1=0.5, 3.3). Childhood pneumonia (RR=2.7, 95% C1=1.1. 6.7) and childhood exposure to coal Iburninp (RR=2.3; 95% CI=1.0. 5.5) were additionall risk factors for ADC. For both ADC and SCC, increased'.risks were associated with decreased intake of $-urotene foods but not for total preformed'vitamin A foods and vitamimsupplements.-JNCI 1985; 74:747 751. Lung cancer is now the fourth most common cancer in women (1) and has been projecaed to be the leading cause of cancer mortality among women by the mid-1980's (2): Causes of lung cancer, other than cigarette smoking (3), have not been, clearly identified, but associations with exposure to passive smoking (4-6), exposure to combus- tion products of heating and cooking fuels (7), and occupational exposures (8-10), have been suggested. In addition, lung "scarring" (11) and a low dietary intake of ,6-carotene (12-14) and preformed vitamin A(15-17) may increase the risk of lung cancer. This paper reports a case-control study of ADC and SCC of the lung in white females in Los Angeles County. Each of the above-mentioned factors was investigated. METHODS Female patients diagnosed'with primary ADC or SCC of the lung were prospectively identified by the CSP, the population-based tumor registry for Los Angeles County (18), between April 1, 19811, and August 31, 1982. On the basis of information collected routinely by the CSP, we limiledeligibility to white Los Angeles County residents, with no history of cancer (other than non-melanoma skin ancer), andd under age 76 at diagnosis; we verified these variables at interview. We also excluded cases if they were born outside the United States, Canada, or Europe; were not English-speaking; or were not residents of Los Angeles County at the date of diagnosis. A total of 490 eligible cases were identified. Of these patients, 190 had died or were too ill to participate by the time we contacted their attending physician. Permission was granted to contact 272 of the remaining 300 patients. Eight patients were not located, and 44 refused to be interviewed so that we obtained completed question= naires on 220. On the basis of information on the CSP abstract, no significant differences were noil between those interviewed and those not interviewed in terms of age, marital status, religion„and smoking status recorded on medical records. However, those who were not interviewe&were more likely to have distant metastases att the time of diagnosis (58%) compared to those who were interviewe& (Il%):, Comparable percentages of eligible SCC (43%) and ADC (46%), patients were interviewed.. We selected one individually matched neighborhood control for each interviewed case. The control had to fulfill all the criteria given above for cases (with reference date taken to be the same as that of the matching case) and; in addition, was matched with the case on date of birth (t5 yr of birth date): Our control seltction algorithm defined a specified sequence of houses to be visited in the neighborhood where the case lived at date of diagnosis. Our goal was to interview the firsn eligible resident in this sequence., If no one was home at the time of the visit, we left an explanatory letter and made a follow-up visitt after several days. For any patient, 80 housing units were 'visited and 3 return visits were made before failure to secure a matched control was conceded. In 150 instances the first eligible person agreed to paiticipate, in,55 instances the second eligible control in the sequence was interviewed, and in 15 instances the third eligible control was interviewed. Cases and controls were interviewed on the telephone with the use of a structured questionnaire designed to elicit information on personal smoking habits, exposure to passive tobacco smoke, lung diseases, dietary intake of vitamin A, types of heating an&cooking fuels ever used, and reproductive history. We also obtained a lifetime history of all jobs (job title, activities, and exposure) of at leaso 6 months' duration. For childhood passive smoking exposure, we asked about the smoking habits (i.e., amount and years of smoking) of father, mother, or other household members AssREvlAnows VSED: ADC=adenovrdnoma; CI=confidence intenvali CSP=University of Southern CGlitoania/I,u. Angeles County Cancer Surveillance Program; RR=relative ruk(s); SCC-.quamous cell ar- dnoma. 1 Receivcd June 11, 1981: revixed November 28, 1984: accepted! December 11. 1984. =5upponed by, gram 5163 from the American Cancer Society, 3Depanment of Family and Preventive Medicine, University, of Southern California School of Medicine, Pukview Medinl Building B;. 2025 Zonal Ave.. Los Angeles. CA 9Ul)33. 4Present addreu: Imperial CGncer Rewarch Fund's Cancer Epide- miology Unit, Radcliffe lnfirmary, Otdord' University, Oxford OX2' 6HE. England. S Wc thank the word-processing pool for preparation of the manu- saipc. 747 JNCI. VOL 74:..NO..4. APR1L~1985

748 Wu, Henderson, Piktf, and Yu 4 when they lived with the respondent during her child- hood and teenage years. For passive smoke exposure during adult life, we asked about the smoking habits of spouse(s) and other household members when they lived with the respondent. Passive smoke exposure at work was assessed only in terms of the average number of hours per day to which the respondent believed she was exposed at each job. The questions on vitamin A intake specifically asked about average frequencies of consumption of 21 vegeta- bles and fruits that are high in S-carotene and 7 foods that connined preformed vitamin A during the calendar year 3 years before diagnosis of the case (19). Pattern of use of vitamin supplements was also assessed for the same period. On the basis of U.S. Department of Agriculture tables of food values for standard portion size (common household measure) of each item (20), we estimated average daily intake of 0-carotene (or vitamin A) by summing the product of the 0-carotene (or vitamin A) content of each food item and its reported frequency of consumption. Quartiles of consumption were constructed on the basis of the intake pattern of the 220 controls. All cases were diagnosed microscopically. Their rou- tine pathology reports were reviewed for mention of lung scarring. Statistical analysis was conducted with the use of multivariate logistic regression methods for individuallyy matched case-control studies (21). RR were estimated by odds ratios. A case-control pair was excluded from any given analysis if the information for either the case or the control was not known for the relevant variable(s). Since personal smoking will often; if not always, confound other associations, RR for other factors were always given after adjustment was made for personal smoking. For ADC, RR for certain factors were given separately for nonsmokers, ex-smokers, and current smokers; this was not done for SCC because the numbers of non- smokers and ex-smokers were too few. RESULTS We interviewed 149' ADC and 71 SCC cases and their matched controls. The mean age at diagnosis was 59.7 years for ADC cases and 61.4 years for SCC cases. The mean ages (at date of diagnosis of the index case) for the respective control groups were 59.5 and 61.1 years. Personal cigarette smoking.-For both ADC and' SCC, rhere was a significant trend in risk aissociated wittv . iocreasing number of cigareues smoked per day and with decreasing age at which smoking began (table II). Both aspects of smoking remained significant after adjustment was made for the other. Passive srnoking.-Families tended to share similar smoking behavior. Controls whose father, mother. or spouse(s) smoked were more likely to smoke, to be heavy smokers, and to stan at a younger, age than controls whose family members did not smoke. For ADC and SCC, after adjustment was made for personal smoking habits, there were no significantly increased risks for having a mother, a father, or spouse(s) who smoked or for being exposed at work (table 2). For nonsmoking ADC cases, we did not observe anyy elevated risk associated with passive smoke exposure from either parerlts (RR=0.6; 95% CI=0.2, 1.7), from spouse(s) (RR=l.2; 95% C1=0.5, 3.3), or at work (RR=1.3; 95% CI=0.5, 3.3). Increasing RR (RR=1.0,,+ 1.2, 2.0) were found with increasing years (0, 1-30, ?31') oL..passive- smoke 'expostue ~ during"adult Iife froin }pouse(s) and at work,,6ut the results were not sta- usucally significant. Since the exposures may have occurred concurrently, the years of exposure represent units rather than chronologic time of exposure. Childhood exposures.-For both ADC and SCC, no significant association was found with history of htng diseases (specifically, asthma, bronchitis, pneumonia, tuberculosis, fungal diseases, emphysema, and lung abscess) diagnosed by a physician at least 5 years before diagnosis of the case. When the analysis was restricted to lung diseases that occurred before age 16 (childhood), a significantly elevated RR for pneumonia was observed for ADC after adjustment was made for personal smoking habits (,RR=2.7; 95% C1=1,1, 6.7); and the RR for SCC (RR=2.9; 95% CI=0.5, 17.4) was in the same direcuon... Parental smoking did not explain this effect. Table 3 shows that for ADC, the effect of childhood pneumonia was most apparent among nonsmoken: Of the 2S TABLE 1.-Persowal swro+l•iep Aabife of eases awd towtrole Smoking status ADC SCC RR 95% CI Case/eontrol RR 95% CI Case/control Nonsmoker 1.0 29/62 1.0 2/30 Ex-smoker" 1.2 0.6.2.3 21/37 7.7 0.8.70.3 8/18 rEurrent smoker 4.1" 2.3.7.5 99/50 35.3" 4.7:267.3 61/23 Current smoker. Na ciQaeettes/day N 1-20 2.7 1.4.5.4 38/28 17.7 2.3.138.2 19/14 t21 6.5" 3.1. 13.9 61122 94.4" 9.9, 904.6 42/9 ~ Current smokerr age started to smoke. yr . >_25 1.1 0.4.3.2 8/14 7.8 0.8. 73.7 6/5 CJ 19-24 2.5 1.0.5.8 22/15 47.1 4.4. 3,98.5 18/7 518 8.0" 3.6. 17.9 69/21 115.7" 9.8. 1371.2 37111 CJ ' Had stopped smoking at least 3 yr before diagnosis year of case. ~ P (linear trend) G001. JNCI. VOL 74. NO. 4. APRIL 1965 - M' N w

i TABLE 2.-Etposrn to passiror nnokinp ia cwu and eontroia ILunp Cancer In Wonien 749 Smoking ssatu ADC SCC Adjusted RR' 95% CI Adjusted RIi° 95% CI Mother smoked 1.7 0.8. 3.5 0.2 0.0, 1.5 Father smoked 1.3 • 0.7, 2.3 0.9 0.3, 2.9 Spouse(s) smokedM 1.2 0.6.2.5 1.0 0.1„7:6 Exposure at the workplace 12 0.8. 22 2.3 0.7, 7:9 ' Adjusted for number of cigarettes smoked per day and age at starting to smoke. • We eliminated from the analysis 15 pairs of ADC and 4 pairs of SCC in which either the case or the control was never married. nonsmoking ADC cases, 8 (28%): gave a history of childhood' pneumonia. Elevated RR,- adjusted for personal smoking habits, were observed for exposure to burning coal used for heating or cooking in a stove or fireplace during the majority of childhood and teenage years (ADC: RR=2.3; 95% CI=1.0, 5.5. SCC: RR=1.9; 95% CI=0.5, 6.5): For ADC, elevated RR were observed in each personal smoking habit category, (table 3): TABLE 3.-RR and 95%conlidenee tinterroala oJADC oJW tanp according to childhood pneu+nonia and coal burni•np by prraoxal nnokinp Aabitr Exposure RR (95% CI) amona: Nonsmoker Ez-smoker Current smoker Childhood pnsnrlmnia• No 1.0 1.4 (0.6, 2.4) 5.1(2.5,10:3) Yes 3.1(1.0, 9:9) 1.5 (02,10.8), 10.9 (2.1, 57:9) Childhcod coal burninab No 1.0 1.6 (0:6. 3.5) 6.3 (3.0,13.3) Yes 8.2 (0.9.11.8) 4.3 (1.0.17.8), 9.5 (2.1, 41.9) ' Before age 16. The analysis was based on 149 caee-control!psirs of ADC. "Includes heating or cooking with coal burned'in a stove or fireplace during childhood and teenage yesrs. The analysis was based on 143 cax-control pairs of ADC. Dietary vitamin A.-Table 4 presents RR for ADC, adjusted for personal smoking habits, by quartiles of indices of vitamin A consumption. Because of the smaller sample size of SCC cases, the indices were dichotomized. For ADC, a significantly increased risk was observed only for those in the lowest quartile of 0-carotene consump- tion (<2,000 IU/day) compared to those in the highest quartile (>4,000 IU/day), but no appreciably ina^tased'risks were observed for those in the intermediate groups. For SCC, an elevated, but not statistically signifinnt. RR was observed' for women wiCh iB-nrotene intake below the median: When those in the lowest quartile of A- arotene consumption, i.e., less than 2,000 IU/day; were compared to those consuming more than 2.000 IU/day, the unadjusted RR was increased to 1.7 (from 1.3), but after adjustment the RR was not greater than compari- sons above and below the median (both RR=l.5). There was no association with an index of total preformed vitamin A (i.e., dairy products, eggs, liver, and vitamin supplements) for either cell type. However, for ADC and SCC, an association was observed for dairy products and eggs (table 4). Other jactors.-W'e could find no association between any occupation or occupational category and risk of ADC or SCC, but there was an excess number of cooks (4 cases and 2 controls) and beauticians (8 cases and 5 controls) among nses; both occupations have been suggested in previous studies. Elevated RR adjusted for personal TABLE 4.-Dietary intake of )learotsnsc totat prr.Iorvned ritamiw A, and dairy prodticts and eggs a+nonp cases and eowtrota A-Carotene• il Total preformed vitamin Ai' Dairy products and egs' Quart e Adjusted Re 96% Cl Adjusted RR' 96% CI Adjusted RR' 95% Cl ADC 1(hish), 1.0 1.0 1.0 2 0.8 0.3,2.0 0.6 0.8,1A 1.7 0.8,3.9 ~, E 1.3 0.6,27 11 06 26 22 1A,48 4 2.6 1.1,6:7 1.2 0.6.F.8 !.7 1.2,6.8 ~ scC N W land2 1.0 1.0 1.0 Sand4 1.5 0.6.3.8 1.0 0.4.2.4 1.6 0.7,&9 . W ~ ' Includes 21 vegetables and fruits: leafy )ettvee, other leafy sreen, broccoli, nrrota, tomatoes, green peas, green beans, lima beans. r J aspara4ua. summer sqnash, winter squash, sweet potatoes and/or yams. green pepper, red pepper, hot red chili pepper, nntdoupe. wuermekm he. nectari and tomato and/or VB 'uice Ansl is was based on 147 pairs of ADC and 68 paits of SCC ~ apnaob na 1 ri ~ eggs, cheese, butter and/or margarine, cream, milk, b.ef and/or calf l iver. chicken and/or turkey liver, and vitamin supplements. ~Includa 'Analysis was based an 147 pairs of ADC and 71 pairs of SCC, d •i ~ Adjusted for number of ciaarettes smoked per day. JNQ. VOL 74, NO. 4. AlRn. 19s5

TSO W'u, H.nd.rsart, Plk., and Yu smoking habits were observed for a history of hysterec- torny (RR=l.7; 95% CI=0.9, 3.2) and nulliparity (RR=L7; 95% CI=0.8, 3.7) among ADC cases and a history of miscarriage (1R.R=1.5; 95%CI=0.5, 4.9yamong SCC cases. Multiple logistic regression analysis was condutted to 'assess the possible confounding effects of personal smoking habits, childhood pneumonia, childhood coal burning, and P-carotene intake. The results were similar to those when each factor was adjusted for personal smoking habits alone. DISCUSSION This case-control' study examined risk factors for the two main cell types of lung cancer in women-ADC and SCC. Although histologic typing was done by the individual pathologist at each participating hospital, studies comparing interobserver and intraobserver varia- bility in cliassification of lung cell types reported a high concordance rate for cell types other than large cell carcinoma, which was excluded in this study (22, 23). In this study population, about half of ADC and alntost ` all of SCC can be attributed to personal smoking habits; _ the amount smoked and the age at which smoking began were strong determinants of risk of disease. However, there are marked' differences in the strength of association between smoking and cell type of lung cancer, as has been noted previously (21, 2S). The role of passive smoking in the etiology of ADC among nonsmokers is not clear. Our data are not consistent with the findings with regard to nonsmokers obtained by Hirayama (4) and Trichopoulos et al. (5) who reported a twofold to threefold increased risk due to passive smoking. However, the histology of the cases in these studies is not clear, and their data suggest that any effect of passive smoking is larger for SCC cases (3, 6), Of our 29 nonsmoking ADCtxses, 12 were bronchoalveolar cell carcinomas, and this cell type is specifically men- tioned by Correa et al. (6) to have a weaker association with passive smoking. The effect of passive smoking by cell type of lung cancer needs to be investigated f urther in studies with much: larger numbers of nonsmokers. Childhood lung disease may have a role in lung cancer etiology: Certain features of the lung of a child (e.g., susceptibility to airway closure and high peripheral resistance) might make it more vulnerable to residual abnormalities from respiratory illness (26). This notion is supported by observations that both smokers and nonsmokers with childhood respiratory diseases have impaired lung function capacity, that their rate of decline in ventilatory function capacity with age is more rapid than that in individuals without childhood respiratory problems, and that they have higher rates of clinical~ diagnosis of chronic obstructive pulmonary disease (27, 28). Women with childhood respiratory probltrms may have incurred epithelial damage to the airway resulting in airway hypenrcactivity and are more susceptible to other insults to the lung. We cannot rule out the possibility of a chance finding or of preferential recall of JNCt. VOL 74, NO. 4: AMUL I995 childhood pneumonia by cases. However, our data appear to be internally consistent, since we found a significantly higher frequency of' lung scarring men- tioned in the pathology reports among cases with previous childhood pneumonia (12/30=40%) compared to those without (39/1'89=2i%): The association of lung cancer risk with exposure to coal heating or cooking warrants further investigation. Although coal was identified as the major heating or cooking fuel used' during childhood and; teenage years off a significantly higher proportion of cases, we did noi have detailed information on the years of use. Excess risk< of lung cancer have been reported for coke oven workers (29, 30) and British gas workers (31) who were heavih exposed to products of coal : carbonization. Studies of men suggest that their lung cancer risk i~ lowered by greater dietary P-carotene (12-1'!, 32, 33) ane vitamin A intake (15, 17, 32; 33), but the evidence fo: women is less clear (12, 13, 32, 33). We observed i significantly increased risk for ADC with the lowest leve of $-carotene consumption and a similar association fo. SCC These results are consistent with findings fo females in Singapore (d2) and in Japan (13), but they ar not supportive of data for females in Hawaii (32) anc England (33). Our observation of no association with at index of total preformed vitamin A(i.e., dairy products eggs, liver, and vitamin supplements) and no associatiot with total vitamin A intake (preformed vitamin A ant $-carotene-data not shown due to domination b preformed vitamin A) is consistent with findings fo females in Hawaii (32). Conflicting findings have ben reported for subgroups of preformed vitamin A foods an supplements. A higher consumption of liver and vitami: supplements has been reported' previously for fernal cases as compared to controls, but the opposite result have been observed for males (33, 34). Our data shoa no case-control difference in the intake pattern c vitamin supplements and a higher consumption of live among cases. Our finding of an elevated lung cancer ris associated with low levels of intake of dairy products hz not been reported for females, although similar resul have been observed for males (15-17). Our results on tF. role of P-carotene and preformed vitamin A were sirnih for ADC and SCC. despite suggestions that vitamin A(c P-carotene)is more strongly protective against SCC tha against ADC (17): Initial reports of an inverse relationship between bloc retinol levels andaubsequent risk of cancer at all sites (3 36) have not been supported by recent studies (37, 36 This situation emphasizes the need to reexamine even tl consistently observed association of vitamin A (or , carotene) intake with male lung cancer. Possible sources of bias in our data must be considere Both lung cancer cases and controls were derived fro population-based samples. However, because this disea is debilitating and rapidly, fatal„ 190 patients had died were too ill to participate by the time of initial contw~ We did not conduct proxy interviews because questio on childhood exposures and dietary history could not assessed adequately. As expected, the group who was n ~o~338228'7

0 inten'iewed was mote likely to have metastatic disease at diagnosis but was similar in all demographic variables measured. In addititsn, information abstracted' from medical records showed similar smoking status for those interviewed and those not interviewed. If cases who were not iinten•iewed because of' poor survival, differed from those who survivect longer and were interviewed in terms of the other risk factors under ;tudy, this could have •' biased our results. However, this appears unlikely since our data showed that histories of childtiood' pneumonia and exposure to coal fires were similar among cases regardless of stage of disease at diagnosis. There is also no evidence that cancer survival is associated with dietaryy vitamin A intake. The etiology of SCC can be explained almost enurelyy by cigarette smoking. Cigarette smoking, however, ex- plaiits only about half of the ADC cases. On the basis of this study, childhood' lung disease and exposure to coal fires in childhood explain at least another 22% of ADC cases. Passive smoking and vitamin A may be involved, but more research is needed to clarify their roles in lung cancer etlol,ogy:. REFERENCES (1) SILVERtERG E:,Cancer statistics, 1982. CA 1982 32:15-31,. (2) HENDERSON BE. Descriptive epidrmiologyy andd geographic pRthology. In: Burchenal JH. Oettgen HF„ eds. Cancer achievements, challenges and prospecu for the 1980's. Vol 1., New York: Grune. 1981:51-69. (d) U.S. Public Health Service. The health consequences of smoking:. Cancer. Washington DC: U.S. Govt Print Off, 1982 [DHEW' publication No. (PHS)82-50179). (,I) HttuYAStA T. Non-smoking wives of heavy smokers have a higher risk of lung cancer: A study from Japan. Br Med, J 1981; 282:183-185. (5) , Ta1QHOt•OULOs D, KALANDIDI A. . SrARR05L, M.ACMAHOtC, B. Lung cancer and passive smoking. Int J Cancer 1981; 27:1'-4. '/6). CORREA. P. PICK12 LW, FOh'THAM E. L1N Y,.HAENSZEL W. Passive smoking and lung cancer. Laneet 1983; ,2:595-597: (i.)' Xu ZY. XtAO HP. Li G. Air pollution and lung cancer in Lisoning Province. Nat1 Cancen lnst Monogr. In press. (8)BRESLOw L,. HoAGUN.L,. RASMUSSEN '('i. AlRAMS HK.Occupa- tions and cigarette smoking as risk factors in lung cancer. Am J Public Health 1954: 44:1'71'-181. (9)'. WYNDER EL, BERG JW. CJnetr of the lung arrl0rfg r10f1-mlOk.lri- t special reference to histologic pauerns.. Cancer 1967: ' Z0:9161-1172. I 110) MENct HR, PtstE MC, HENDERSON BE, JtNG JS: Lung cancer risk ( among beauticians and other femak worke»: drieJ consnsMnic.- tion. J Natl Cancer hnst 1977: 39:142l-142S. t(1'1) AvERtuM O, GARmNaEL L. PARRS VR. Sor cancer of the lung- iiseease over a 21 year period Cancer 1979; 43:636-642: t(12). MACLENNAN R. DA C06TA J, DAy NE. LAw CH., Ne YK. SHAN• : MUGARATNAM IL Riskfj•ttork for lung nncerr in Singapore Chinese, a population with high female incadena rates. Int J Cancer 1977; 20:SS4-860. 113) HtRAYAMA T. Diet and cancer. Nutr CGnce 1979; 1:67-811 (!+) SHERELLE RB„LErrER M. L1u S, et a1: Dietary vitamin A and risk Lung Cancer In Women 751 ofl cancer in the Western Electric study. Lancet 1981; 2: 1185-1190. (15) BIELrcE E. Dieury vitamin A and human lung ancer. Int JlGncer 1975,15561,565. (16) M.ETTLIN.C, GRAHAM S, SM•ANSOK M~:..Viumin A and lungnncer.. JNCI 1979;, 62i 1435-1438. (17) Kt•ALE G. BJEt.RE E. GART JJ. Dieury, habits and lung nncerrisk., Int J Cancer 1983; 31:397-405, (18/ MAc.t. TM. Cancer Surveillance Program in Los Angeles County. Nail Cancer lnst Monogr 1977; 47:99=101. (14). GRAHAM S,.METTUN C. Fiber andother.corlstituentL of vegC:'tabltsin cancer epidemiology. 1!n: Newell GR, Ellison NM', eds. Nutrition and cancer etiology and treatrnenL New York: Raven Press, 1981:189=215.. (20) ADAMS C. Nutritive value of American foods in eommon units U.S. Departmenrof Agriculture Handbook No. 456. Washing- ton, DC: U.S. Depanmenrof Agriculture, 1975. (21) BaEtit.ow' NE. DAY NE. Statistical Imethods in oncer research: Vol I-The analysis of case-control studies. IARC Sci Publ 1980; 32:5-338: (22)I YESNER.. R_ GERST B, AL'ERBACH O. Application of the World Health Organiration classification of lung carcinoma to biopsy muerial. Ann Thorac Surg 1965; It33-49. (23) YESNER R, CARTER D. Pathology of carcinoma o('the lung. Clin Chest Med 1982; 3:257-289. (2I) DOLL R, HILL AB. KREYaER6 L Thrsignificance of cellltype in relation to the aetiology, of lung cancer. Br J Cancer 1957; 11:43-4B: (2S) WYNnER EL, CorEYLS, MASUCHt K. Lung cancerr in women: Present and future trends. J Nail Cancer Inst 1973; 51:391-401. (26) KArrAN M. Long-term sequel0e of,respiratory illness in infancry, and childhood. Pediatr C1in North Am 1979; 26:525-535. (27) Buaaows B, KNUtnoN RJ, LEt,owrrt MD. The relationships of' childhood respiratory'il lness to adult obstructive airway disease. Am Rev Respir Dis 1977; 115:751-759. (28) SAMET JM; TAGER IB„ SPEtgR FE. The relationship between rcspiratory illhess in childhood and chronic airflow obstruction in adulthoodj Am Rev Respir Dis 1983; 127:508-523. (z9), REDMOND CK, GOCCO A, LLOYD JW, RUSH'HW;. Long-term mortality study of steel workers. VI. Mortality from malignant neoplasms among coke oven workers. JI Occup Med 1972. 14:621-629: (30) LLOYD JW: Long•terrn mortality study of steelworkers. V. Respiratory cancer in coke plant workers. J'Occup Med 1971: . 13:53-68. (31) DoLL R, FIxHER EJ, GAMMON W. et al. Mortality of gasworkers w ith special reference to o ncen ot the iung and blsdtltr, chronic bronchitis, and'pneumoconiosis. Br J lnd Med 1965; 22:1-12. (32) HINns MW. Kot.oNEL LN. HANRw JH. Dietary vitamin A. carotene, vitamin C and risk of lung cancer in H'awaii. Am J Epidemiol 1984; ,I 19:227-237:. (3)) GREcoa A. LEE PN; ROE FJ, WttsoN MJ, MELTON A. Compari- son of dietary histories in lung cancer cases and controls with specialirrferrnce to vitamin A. Nutr Cancer 1980; 2:93-97. (34) SMtTit PG, Jtot H. Cancers among users of preprratioeu oostuin- ing vitaminA CGncer 1978;,42:808-811. (35) [ARR JD,SMmi AH, SwtTSEa BR, HAMES CG. Serum vitamin A (rxinol) and cancer incidence in Evans County, Gewgia. JNCI 1981;',66:7-16. (36) WALD N, IDLE M. BOREHAM J. Low serum vitamin A and aubfe- quentriak of cancer. Lancrt 1980; 2:813-815. (37) WtLLErr WC, PoLtt BF, UNDUtwooD BA, et al. Relation of serum vitamin A and E and carotenoids to thrrisk of cancer. N Eng) J Med 1984;310:430-434. ()8). STAHEUN HB, BVESSE, ROSEL F. WIDMER LK, BRAlAQ1ER B. Vitamin A, cardiovascular risk tacton, and morulity. hncrt 1982; 1:394-395. JNCI. VOL 74. NO. 4. APR1L 1985