Tobacco Documents Online

Time Trends In Lung Cancer Mortality Among Nonsmokers and a Note on Passive Smoking t NoTicE Lawr.noe Catllnk*l, AA.A. 2.3 ABSTRACT--1_unq cancer mortsiity rats were oomputed for nonamok.rs in th. American Cancer SocdWs prospecttve study for thr.N 4-year pMiods trom 106o to 1972 aand in ths, Dorn study of wt.rans for three 5-yw psriods trom 1954 ~to 190. Th.n was no evidanee of ~ any trend in ths." ratss by 5-ysar ape groups or for thM total groups. No time trend was observed in nonsmokers for cancers of other sNecl,d sitaa sxcspt for a devsaas In cancer of tM utsrus. Compared to norumokinq women marr/sd to nonsmoking husbands, nonsmokers manied to smoking tws- bands showed very little. If any. increased risk of lung oancir.- JN C I 1981: 66:1061-1 oEB: Mortality rates from lung cancer in men in the United States have been rising steadily since 1930 (the first year these cancers were classified separately), and in women since the mid-1960's. It has generally been accepted that the major reason tor the increase has been the cigarette smoking patterns which began in young men around World War I and in young women in the 1!930's and 1940's. A large body of evidence from epidemiologic and pathologic studies on smokers con- firms this concl'usion (1): A recent estimate of the percentage of cancers attributable to smoking in men was 34.5% for total cancers and 82.8% for lung cancer. In women the comparable percentages were 5.4 and 43.1% (2), This analysis was based on data from the large epidemiologic study of the ACS and covered the period 1967-71. It was based on a number of assump- tions than would give slightly different figures if the smoking distributions in the study population differed from those of the general population or if smoking distributions changed in the late 1970's compared to the late 1960's (as they indeed have in women). There has been a suggestion, however, that the lung cancer trend in nonsmokers has also increased in the United States over the years. Fnstrom (3) stated that "a more complete understanding of lung cancer etiologyy is needed." This analysis indicated a large relative increase in lung cancer mortaliry, in nonsmokers in both white men and white women between 1914 and 1975 on the basis of an interpretation of data in samples of national mortality statistics and several epidemiologic studies in different periods of time (3). Enstrom recognized that most of the increase occurred between a 1914 survey of death registration areas in 24 states and national mortality statistics reported in 1935 and that most of that increase was probably attributable to incompleteness of reporting lung cancer and to changes in diagnostic criteria. Nevertheless, the possibility exists that lung cancer is increasing in nonsmokers who have had increasing exposure to other factors-occupational exposures, This mater+al may be protected by copyrigM hn (Tiqo 17 U.S. Code~ general air pollution, and perhaps even to passive smoking (inhaling the smoke from smokers). Even if these factors were related to the alleged increase in lung cancer, they could have had only minimal effect on the upward trend for lung cancer in men, since the mortality rates among smokers and nonsmokers differ so greatly: Moreover, in the last 50 years and until recently, most men had a history of cigarette smoking. Among women lung cancer rates remained low up to about 1960. Since then, there has been a threefold increase in rates attributable in large part to the changes in smoking patterns among women during the preceding two or three decades. In this paper, information is provided on trends for lung cancer (and cancers of several other sites) in nonsmokers over a 12-year period (1960-72) from data in the prospective study of the ACS. In addition, data for nonsmokers from the Dorn study of veterans for the years 1955-69 are given. While such data do not provide evidence over a very long time span, they are based on the two largest prospective studies in the United States and cover a 174-year period from 1955 to 1972. MATERIALS AND METHODS Procedures in the collection of data in the prospec- tive study of: the ACS have been presented in a number of publications (4-6). There were 94,000 male and 375,000 female nonsmokers at the start of the study. In the ACS study, a'•nonsmoker" is one who reported he or she had never smoked or smoked only occasionally, but had never smoked regularly. Classification was made as of the start of the study, and very few nonsmokers reported that they started to smoke on any of four later questionnaires. Enrollment of subjects in the ACS study began in October 1959 and extended through March 1!960. Fol'- low-up was complete for 98.4% of all subjects through June 1971 and 92.8% complete for the 12th year of the study. Deaths were reported by the ACS volunteers, and death certificates were obtained from state health de- AaattcvutvoN usw ACS- American Cancer Society. . " Received Oaober 23, 1980; accepted: January, 26, 1981. ' DDepartment ot Epidemiob`y, and Sutistics. American Cancer Seciety. 777 Third Ave., New York. N.Y. 10017.. ' I thank Eugene Rogot for supplying the data (or the Dorn studs of vetaans and Henry Vasqua and L-inda Merlino for atsisuing the ptocessing of the data in this study. 1061 JNd: WOL 66. NO: 6., JUNE 1961 2+C :338Z172

1'062 Guflnksl partments. Mortality data for this analysis begin with observation starting on July 1, 1960. Data are presented for three 4-year periods: period 1, July 1, 1960; through June 30, 1964;, period 2. July 1, 1964, through June 30, 1968; and period 3, July 1. 1968, through June 30, 1972. Person-years of observatson in nonsmokers and deaths at single years of attained ages 35-89 years were computed and combined by 5-year attained age groups. In the Dorn study of veterans, questionnaires were mailed' starting in January 1954 to 293,000 veterans holding U.S. Government life insurance. About 65% of the questionnaires were received over a period of severil', months. In January 1957 a second questionnaire was mailed to those not responding to the first mailing and the replies raised the total to 85% (7). About 54,000 of those who replied were nonsmokers. The same classification of nonsmokers was used in this study as was used for the ACS study. Person-years of observa- tion and mortality by single years of attained age were computed starting with January 1, 1955, for the re- sponders to the first mailing and starting with January 1. 1958, for the responders to the second mailing. Death certificates were supplied to the Veterans' Ad- ministration in support of insurance claims through 1962. For the period 1962-69, death certificates were obtained through field work at health departments by. ACS personnel (8): Death rates by 5-year age groups were adjusted to the distribution of the stationary population (,L:) of white men and white women of ages 35 years and over in the abridged life tables for the U.S. popul'atian in 1965 (9). Differences in death rates for periods I and 2 and periods I and 3 were tested for significance at the P<0.05 level by the Mantel-Haenszel procedure (10). RESULTS Tlrts. Tnndk In Lung Cancar Mortality Among Nonsrnok.n Table I shows the 5-year attained age death rates for lung cancer among nonsmokers in three periods of time. The table includes men and women in the ACS study and men in the Dom study of veterans. There were 195 deaths from: lung cancer among male non- smokers and 564 deaths from lung cancer among female nonsmokers in the ACS study during the 12- year period. There were 168 deaths from lung cancer among nonsmokers in the 1!5-year period in the Dom study of veterans. Some of the rates computed for 5- TeBLE 1-DeatA rates fmin ltiwp cancer per 100.000 person-years among worsmokers. apa 35-89 yeara, by time period: ACS prospective study and thc DorR study of aeteruna ACS prospective study' Attained a8e eroup, yr' Period 1: Period 2: Period 3: July 1960- July 1964- July 1968- June 1964 June 1968 June 1972 Dorn's study of veteranss Period 1: Period 2: Period 3: Jan. 1955- Jan. 1960- Jan. 1965- Dec. 1959 Dec. 1964 Dec. 1969 Males 35-39 40-44 - (8:7) (14.3) 45-49 (4.0) (5.1) 50-54 (5.3) 8.8 (8.8) 56-59 10.5 11.6 8.3 (12.0) 60-64 17.0 17.3 17.5 112 (10.7) 66-69 18.6 29.4 34.3 25.1 16.9 70-74 32.3 26.4 19.2 39.9 40.5 76-79 32.7 41.5 58.6 (37.8) (15.0) 80-84 (47.9) 106.8 51.9 - (200.6) 86-89 61.8 152.7 (69.9) (595.2) No. of deaths 52 74 69 38 52 Ase-atandardisad death rate 12.5 18.5 15.8 189 13.4 Females 36-39 40-44 - (3.5) (3.5) 45-49 6.9 (3.3) (1.6) 50-54 6.2 7.7 (3.0) W59 7.4 8.0 6.8 6Q-6i 14.0 12.3 14.5 66-69 15.6 152 17.7 70-74 19.4 21.1 22.0 76-79 37.3 30.5 36.3 80-84 51.5 45.1 40.8 W89 53.4 44.6 59.5 No. of deaths 175 184 205 Ase-standr<rdised death rate 13.8 12.9 13.1 (103.5) (8.6) (48.0) 43.5 382 472 (20.6) 78 19.6 ~ ~ ~ w. Cj GO ~ ' Some 5-yr aQe eroupe were combined in the standardization of ratss to avoid 0 cases in these aroups. ~ NY+nbers iw pareetAeses indicate <5 deaths in group. ~ w JNQ,, YOC. 66. NO. 6. ]UNE 1961

Lung Csna.r Tr.nds In Non.mok.n 10( year age groups were small and subject to considerable sampling variation. There was no appearance of any consistent increase in the lung cancer death rate among nonsmokers with ume by 5-year age groups. The age- standardized rates for males shown in table I and in text-figure 1 showed no trend~: The rates for women were based on many more cases, and the age-standard~ ized rate was virtually the same in all three periods. The differences in rates between periods I and 2 and periods I and 3 were not statistically significant in both the ACS study and the Dorn study of veterans. The analysis was based on the underlying cause of death on death certifiotes. The death rates for the three periods were also standardized to the distribution of the stationary population of white men and women combined, of ages 35 years and over, in the abridged life table for the U.S. population in 1965. This standardization raised the ntes frn males slightly and decreased the rates for females slightly, but it changed the pattern of the trends very little. An atterhpt was made in the first 6 years of follow-up in the ACS study to obtain confirmation of diagnosis for all cases with cancer from physicians who signed the death certificates or from hospitals in which death occurred. Information was received confirming the primary site of cancer in 78% of the cases, and microscopic confirmation was obtained in 69% of the cases in the first 6 years (6). Table 2 shows a comparison of the death certificate diagnosis and the final diagnosis from the medical report. Among nonsmoking men, 74 were reported to have died of lung cancer according to the death certificates. Six of these (8.1%) were reported to have died of cancer of another site on the final report. However, 9 (0.8%) of the deaths reported as being due to cancer of a site other than lung on death certificates proved to be due to lung cancer on the final report. Thus among nonsmoking men there were 74 deaths from lung cancer reported on death certificates and 77 deaths from lung cancer according to the final medical report. 3 so oamt stuM ..c.s 6ruM, MEN 01" ACS S7UO'Y,, o so 0 lo k TABLE 2-Lisnp cancer dfat/u among worinoken in firat 6 years qf attidy on death aeriiJi,uitea and on Jira! rcporr. Final De+th certificate diagnosis report Lung cancer Other cancer disenosis No. Percent No. Percent Males Lung eancer 68 91.9 9 0.8 Other cancer 6 8:1 1.153 992 Total 74 100.0 1.162 100.0 Femsles Lung eancer 169 83.3 10 0:2 Other cancer 34 16.7 6.160 99.8 TocaP 203 100.0 5.170 100.0 lin women the picture was somewhat different. Two hundred and three cases of lung cancer among non- smokers were reported to be lung cancers on death certificates, and 34 (16.7%) were reported to be cancers of other sites on the final medical report. A smaller number, 10 (0.8%), of those cancers that were reported as being of a site other than the lung on death certificates were reported to be lung cancers on the final report. Thus on death certificate reports, 203 nonsmoking women were reported to have died of lung cancer in the first 6 years. On the final report, 179 (a decrease of 11.8%) were reported to have d'ied of lung cancer. About one-third of the 34 females whose causes of death were attributed to lung cancer on the death certificates and changed on medical confirmation died from breast cancers. However, breast cancer was under- diagnosed on death certificates in nonsmoking women. There were 1.310 breast cancers reported on death certificates in the first 6 years of the study and 1,371 on the final report. Table 3 shows the age-standardized rates for total mortality for all cancers and for cancers of selected sites among nonsmokers in the three time periods. Overall mortality in men decreased 3% from period' 1 to 3. This slight difference was statistically significant at the PC0.05 level because of the large number of deaths involved. None of the differences in total cancer or in cancers of other sites in men in table 3 between periods 1 and 2 and periods I and 3 were statistically signifi- cant. Women had an 8% decrease in total death rates between periods 1 and 3. The difference in rates was statistically significant. The decreases in total cancer and uterine cancer between periods I and 2 and periods I and 3 were statistically significant. None of the differences for cancers of other sites were statistically significant except for the 29% decrease in cancers of the buccal cavity, pharynx, larynx, and esophagus between periods 1 and 3. YM Pssshr. Smoking TE%T•FlGURL t...-l-una caflcEr IDoriali[y. rates in three 4-yf pCrlOdl for nonsmokers in the ACS prospecuve study and for nonsmokers A number of studies have established that non- in three 5-yr periods in the Dorn study of vercrans. smokers exposed to smoke from cigarettes in a poorly JNQ, vOL 66. NO 6. JUNE 1%1

1064 Caritnk.l TABLE 3-Trendr in mortality ratu f*one eereerm of ielscttd rittt ix 6lree tiMt penoda for wow.mr~kera A CS svr stvdv: 196o-7 r*afa«t' No. of Period' 1! Period 2: Period 3: Parameter deaths July 1!960- July 1964- July 1968- June1964 June 1968 June 1972 Males Total desths 19,805 1,608.7 1.588.6 1.b69.9 Total cancers 8,151 247.8 252.4 251.6 Cancers of bucca)iavity. pFiarynz. larynx, and esophagus 62 6.86 6.79 5.46 Ce,ncer of colon-rectum 636 51.9 46.0 60.4 Cancer of pancreas 199 15.0 17.6 14.0 Cancer of prostate gland 573 69.5 63.1 59:6 Fem.les Total deaths 62.966 1.494.5 1,485.8 1.374.2 Total cancers 13.275 317.9 304.6 298.1 Cancers of buccal cavity. pharynz, larynz, and' esophaaw 159 4.88 4.21 3.48 Cancer of colon-rectum 2,429 68.0 59.8 56.7 Cancer of pancreas 688 17.4 16.2 14.8 Cancer of breast 3,186 69.3 68.0 76.0 Cancer of uterus 833 22.1 18.4 15.0 ventilated room will show increased' levels of carbon monoxide in their blood. These higher levels of carbon monoxide can result in deterioratiom of psychomotor performance. Many nonsmokers have acute eye and throat irritation responses in the environment of ciga- rette smokers (11). One paper reported changes in lung function tests in people classified as passive smokers compared& to nonsmokers, and these changes were interpreted as demonstrating a greater reduction in the function of small airways (12). Hirayama (13) reported lung cancer mortality ratios in Japan ranging up to 2':1 in nonsmoking women with husbands who smoked 20 or more cigarettes a day compared to nonsmoking women with nonsmoking husbands. Trichopolous et al. (I4) reported similar findings in a case-control study in Greece. A similar analysis was made of nonsmokers in the ACS study, even though classifying nonsmoking women on the basis of the smoking habits of their husbands is not an accurate measure of their degree of passive smoking. Moreover, exposures in Japan and Greece may be very different than they are in the United States. Lung cancer mortality among persons who were married to cigarette smokers was compared with the mortality among those married to nonsmokers. A total of 176,739 nonsmoking women were identified who were married a) to men who never smoked, b) to men who currently smoked cigarettes regularly but less than 20 cigarettes a d2y, and c): to men who currently smoked 20 or more cigarettes a day. Most husbands had smoked for 20 or more years before the study began, and presumably their wives were more likely to have been passive smokers than were the women married to nonsmokers. Twenty-eight percent of the husbands of nonsmoking women were nonsmokers compared' to 21% of men in the total study population. Table 4 shows the results of this analysis. Expected numbers of deaths were based on the lung carrcer rates for the 12- year period' (1960-72)„ by 5-year age groups of' the JNCt. VOL. 66. NO. 6. )t'NE 1981 women with nonsmoking husbands. No attempt was made in this first analysis to adjust for other possible confounding factors. The observed versus expected lung cancer mortality ratio for women whose husbands smoked less than 20 cigarettes a day was 1.27; for those whose husbands smoked 20 or more cigarettes a day, it was 1.10. Neither of these differences was statistically significant at P<0.05 by the Mantel-Haenszel procedure. A separate matched-groups analysis was made of the lung cancer deaths among the same 3 groups of women to eliminate the possible effects of potential confounding factors. The women in the 3 groups were matched by age (5-yr age groups), race (white, non- whice), highest educational status of husband or wife (not a high school graduate, high school graduate, or higher), residence (rural, not rural), and husband occupationally exposed to dust„ fumes, or vapors (yes or no). The analysis was restricted to nonsmoking women who were not sick and who had no serious disease at the start of the study. "Adjusted" numbers of deaths for each matched diad were computed, as described in other publications (1'3, 16). In this pro- TAaLL 4.-Ob~ nerm upat.d' heW screer d.atJia among woweewkiep wvnW. Wa/t eipnrette eMok-p Ayeba*ds: ACS stLdy. Jaeo-zs' Husband Husband Husband Parsmeter did not smoked <20 smok.d ?M unohe c4arettes/ c+ga+'etw/ day day OMerred dst}u 65 39 49 Expected ~ deaths 65.00 30.67 44.67 Mortal ity ratio 1.00 1.27 1.10 ' Expected deaths ate based on the lung cancer tates by 5-yr ese srottps in ..omen with non.mokinQ husbands applied to the peFaon.years of wornen with smoking husbands. TAe 96% confidence limit for women with husbsnda smoking <20 eit;arettea/day was 0.86, 1.89: for women with husbands smoking z20 eiprettes/day, it was 0.77, 1.61.

Lung Cancer Ttwtde In Nonsmokers tC TAsLE 5-Matched proup itvdy: Agjvsted' twp faneer d.atJtW a"wo+tQ women witA nonamodrirp bwbawd+ +RateAcd with sswwen mib4 rnlokinp kti.bandr Group No. of ~ eanoer deaths Rstio, P` Nonsmoking husband 26.6 1.00 Husband smoked <20 35.0 1.37 NS eis.rtttea/tisy Nonsmoking husband $4.5 1.001 Husband smoked ;z20 86.s 1.04 Ns eirisr+ctta/day ' See text tor definition of adjusted d..t3n. ~ Matched on the basiu of a)..ite's 5-yr ase sroup, b) ht»band's oeup.tiorulI exposure. c) highest educational level of husband or wife, d) tsa, c) urban-rural residence, and 1) ab.enoe of .erious diasa.c at the start of the study.. ` NS=not ugttif'ii~ant. cedure women whose husbands never smoked were compared to women from each of the 2 groups in which the husband smoked; cigarettes. The number of lung cancer deaths in each matched diad was adjusted to the proportion of persons for each group and summed over all groups to give an "adjusted ' number of lung cancer deaths. Variances were computed for each of the matched groups and summed over all matched groups, and' probabilities were computed under the null hypothesis of observing no differences. The results of this analysis are shown in table 5. The ratio of adjusted lung cancer deaths in women whose husbands smoked less than 20 cigarettes a dayy to those in women whose husbands never smoked was 1A7. The comparable ratio for women whose husbands smoked 20 or more cigarettes a day was 1.04. None of these differences were statistically significant (P70;05).. DISCUSSION Data from the two prospective studies reported in this paper indicate that the age-adjusted mortality rate for lung cancer in nonsmoking men, 35-89~ years old was between 12 and 19/100,000 in the 1950's and 1960's. The observed rate for women was about 131 100,000. The rate may actually be about 10% less because lung cancer in nonsmoking women raay be over-reponed on death certificates. The lung cancer rates shown in table 1 may be slightly different from those shown in other publications because different years, age groups, or methods of standardization were employed. The rates for male and female nonsmokers by age group in this analysis were in about the same range as that of the 1958 rates for nonsmokers in Haenszel's report of a 10% sample of death certificates in the United' States (17, 1B): The 1966-68 estimates derived by Enstrom from several sources are not directfy com- parable because of a different classification of non- smokers ("never smoked cigarettes") (3); The male rates in the period 1968-72 are about one-half those reported by Enstrom for active Mormons in 1968-75 (19). Enstrom defined active Morm:ons as a cohort that can be considered "almost entirely as white males who never smoked," and he used: this cohort to serve as the nonsmoker lung cancer rates in the 1968-75 period "in: lieu of recent national mortality data on nonsmokers." The mortality rates for lung cancer in: both male and female nonsmokers by, 5-year age groups showed no consistent trends over the period in this study. Long-term effects of passive smoking are difficult to establish because of the problems in classification. It may be misleading to classify a women as a passive smoker or not on the basis of her husband's smoking habit. Wives of nonsmokers may be more exposed! to cigarrtte smoke of others than wives of cigarette- smoking men; wives of smokers may be very little exposed to; the cigarette smoke from their husbands or others. In addition, 13% of the women nonsmokers who died of lung cancer in the ACS study reported that they were previously married, and the classification of their exposure to their husbands' smoking may not be pertinent. In autopsy studies of cigarette smokers, there was a dose-related spectrum of histologic findings, including basal cell hyperplasia, metaplasia, and cell5 with atypi- cal nuclei in the mucosa of' the tracheobronchial tree that may lead to invasive carcinoma. In contrast,, advanced histologic changes in specimens from the tracheobronchial tree, such as lesions with six or more cell rows, lesions having 50% or more cells with aty;pical nuclei, and' carcinoma in situ, were found in less than 0.1% of the slides of nonsmokers (20). Since there is such little variation in the appearance of these histologic changes in nonsmokers of different age, sex, and residence, it seems doubtful that those nonsmokers who had been heavily exposed to cigarette smoke from others in their lives could have had many more precursor lesions for the development of lttng cancer than nonsmokers not so exposed. Therefore, there is evidence from, these studies that passive smoking cannot play more than a very small rolt in the development of lung cancer. Mortality ratios for male smokers of less than 10 dgarrttes a day compared to those of nonsmokers range from: 2 to I in Japan to nearly 5 to 1 in the United States. Mortality ratios in women are even lower. It appears unlikely on a biologic basis, therefore, that wives with husbands who smoke 20 or more cigarettes a day can have mortality ratios that approach those of regular cigarette smokers. To obtain data on passive smoking in nonsmoking women, an epidemiologic study shoul& be specifically designed to measure their exposure as accurately as possible. This is very difficult to do. Neither the Japanese study nor the ACS study was designed to obtain definitive information on passive smoking. Data for lung cancer risks in occupationally exposed; nonsmokers compared to nonexposed nonsmokers art JNQ. VOL 66. NO 6. JUNE 199' zo~3,s21,7s

pltl! Garfink.l not very extensive. One study showed an increased risk in heavily exposed asbestos workers on the basis of a ~ small number of cases (21). tl It would be interesting to continue studtes of lung cancer trends in nonsmokers over a long period of time, but,the major public he2lth problem in lung lancer is With cigarQtte srnokeis. Cigarette smokers who. -Are occupationally exposed' to asbestos have a greatly elevated risk compared to the risk among cigarette smokers not so exposed (21),. Lung cancer rates are rising at an alarming rate in women who smoke cigarettes. Educational efforts should focus on smoking- cessation programs for these groups and particuularly on persuading young pe+ople not to stan. Even if the estimates from this analysis are in error and there was a slight increase in lung cancer trends in nonsmokers, it did not appear to be an important problem in the overal' picture 6or the time period of this study. REFERENCES (1) Public Health Service., Smoking and health. A report of the Surgeon General. Washington. D.C.: U.S. Govt Print O(f. 1979 (DHEW publication No. (PHS)79•50066).. (2) HAMMOND EC. SEIDMANH. Smoking and cancer inn the United States. Prey Med 1980: 9:169-173.. (3), EwsTtltoM JE. Rising lung cancer mortality among nonsmokers. JNC] 1979: 62:755-760. (4) HAMMOND EC. Smoking in relation to the death rates of one million men and women. Natl Cancer Inst Monogr 1966; 19: 127-204. (5): HAMMOND EC• GArtrtNCat. L. Coronary heart disease, stroke and aortic aneurisrn. Factors in the etiology. Arch Environ Health 1969; 19:167-182. (6) GArtrtN[EL L. Cancer mortality in nonsmokers: Prospective study by the American Cancer Society. JNC 1980: 65:1169- 1173. JNp. VOL 66. NO. 6. JUNE 1961 (`.) KAHN HA. The Dorm study of smoking and morulity among U.S. vexrans: Report on eight and one-half years of observa• tion. Natl Cancer Inst Monogr 1966: 191-125. (8) Roeo7 MA. MuatuY JL. Smoking and causes of: death among IJ.S. veterans: 16 years of observation. Public Health Rep 1980: 95:213-220. (9): Public Health Service. Life tables. In: National Center for Heahh Statistics. Vital statistics of the United States-1965. Vol t1. Mornlity, part A. Washington• D.C.: U.S. Govt Pnnt Off. 1967:1-8.. (10) MANTtL N. HALNSLEi W. Statistical aspects of the analYsis of data from retrospective Mudies of disease. J Natl Cancer Tnu 1959; 22:719-748. (17):Public Health Service. Involuntary smoking. ln: The health conseqtrnces of smoking. 1975. Atlanta. Ga.: Center for Disease Control,, 1975:83-112.. (12) Wttrrt JR. Fttots HF.,Small-airways dysfttnction in nonsmokers chronically exposed to tobacco smoke. N EngI J Med 1980: 502:720-723: l13) HuuvAMA T. Non-smoking wives of heavy smokers have a higher risk of lung ancer. A study from Japan,: Br Med J 1981: 282:183-1854 (14)TItCHOt'Ot:LOS D• KALANDrDrA. SfAaROs L. MACMAHON B. Ltsng cancer and passive smoking. tnt J Cancer 1981!: 27:1-4. (15) HAMMOND EC. GAartNttEL L• SnDMArr H. LEw LA. Tar and nicotine content of cigarette smoke in relation to death rates.. Environ Res 1976; 12:26l-274. (16) HAMMOND EC, GAStnNCCL L Aspirin and coronary heart disease: Findings of a prospective study. Br Med 1 1975; 2:269-274. (17) HAENStu W, LovsLAlvD DB. StsttuN MG. Lung-cancer mornlityy as related to residence and smoking hisaories. 1. White males. J Natl, Cancer Inst 1962: 28:947-1001. (18): HAENS2Et. W TAiutE>< KE. Lung-cancer mortality as related to residence and smoking histories. It. White females. J Natl; Cancer Inst 1964: 32:803-838. (19) E.rsntoM JE. Cancer and total mortality among active Mormons. Cancer 1978: 42:1943-1951. (20) Autrt.Aa+ O. GArtrtNCCt L• HAatMOND EC. Qtanges in bronchial epithelium in relation to cigarette smoking, 1955-1960 vs. 1970-1977: N Engl J Med 1979: 300:381-386: (ZI). HAMMONDEC.,SE1ICOiF 1J', SEIDMAN H. Ajbestosexpofures ctg• atrtte smoking and death ntes., Ann NY Acad Sci 1979; 330:: 474-490.: 9':