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2O6 STELLMAN Table 5. Tar exposure indices used by various authors Reference Indices Bross & Gibson (1968) 1. Quantity-duration combinations (low, medium, high) 2. Filter versus nonfilter High, 25.8-35.7 mg; medium, 17.6-25.7 mg; low, below 17.6 mg Tar rating of current cigarette Z'(quantity x duration x k) where k= 1, below 15 rag; k = 2, 15-24 mg; k= 3, above 24 mg 1. Lifetime filter versus mixed filter and nonfilter versus lifetime nonfilter 2. W{thin-country quintiles of: Z (tar x cluantity)/.£' (quantity) combined across five countries Hammond etal. (1976, 1977) Mushinski & Stellman (1978) Kunze & Vutuc (1980) Lubin etal. (1984a) current cigarette (Hammond et al., 1976; Mushinski & Stellman, 1978), to fairly elaborate scoring systems presented by Lubin et al.. (1984a), and Kunze and Vutuc (1980). Finally, it has been repeatedly demonstrated and emphasized that people do not smoke identically to machines, and that the tar yields upon which machine analyses are based do not represent the true quantities of particulates or concentrations of vapour phase toxi- cants to which people were actually exposed (Kozlowski et al., 1980; Benowitz et al., 1983). At best, machine-determined yields give relative representations of degree of exposure to cigarette combustion products, such as tar. Since, as has been seen in the preceding sections, the results of studies using different dosage measures are remarkably consistent, we may reasonably conclude that the basic principle that relative risk for lung cancer is in rough proportion to tar yield has been confirmed, despite these many difficulties and the disparities between studies, and that age-specific lung cancer rates may be expected eventually to reflect the falling average tar levels in many Western countries. Outcome In both case-control and follow-up studies, specification of the outcome under investiga- tion is not trivial and may strongly influence interpretation of results. In the series of studies by Wynder and colleagues, and in those by Kunze and Vutuc, lung cancers were classified as Kreyberg Types I or II, the former invariably exhibiting a stronger dose- response to quantity of cigarettes smoked per day. If these observations are correct, it follows that any ameliorative ettect ot lower tar yaelc~ will De oI lesser importance /or adenocarcinoma of the lung than for squamous-cell carcinoma. Other etiological factors Smokin~ is the maior cause of lung cancer in the populations studied, but it is not the only cause., Few of the studies mentioned have made adjustment for exposure to other factors related" to occupation, environment, or nutrition. We have recently shown (Stell-

CIGAREq-FE YIELD AND CANCER RISK 207 man, 1985) that smokers consume foods rich in vitamins A and C much less frequently than nonsmokers. Since vitamin A and similar compounds have been suggested as possible inhibitors of epidermoid cancers, it may in the future be desirable to examine dietary intake along with smoking history. None of the studies reviewed here have done so. Other confounding factors Most of the studies have adjusted for age and sex, but few have examined other potential biases in selection of subjects, differences in social class between cases and controls, etc. These are factors which, especially in hospitalized populations, can strongly affect smoking habits (Wynder et al., 1984). Considering the consistency of results, despite the variety of study designs and populations summarized above, it is not likely that these confounding fachors have played a major role in the studies summarized here. However, it is important to keep them in mind when designing future studies. CONCLUSIONS In three series of case-control studies and three prospective studies conducted in the USA and Europe, the relative risk for lung cancer was found to be consistently lower in both male and female smokers of lower-yield cigarettes. This basic finding continued to hold irrespective of the many different ways in which dosage was expressed, whether qualitatively (filter versus nonfilter) or quantitatively (with explicit tar yields or ranges). Risks for other types of cancer, notably mouth, larynx and bladder, were also found to be lower in smokers of filter cigarettes in a number of North American and European studies. This is all the more remarkable since the designs of studies differed considerably, and the designation of cigarette tar yields for specific cigarettes reflected only crudely true lifetime exposures for individuals. Smokers reaching lung cancer age during the past few years have almost invariably begun smoking nonfilter cigarettes, and many switched to filters during the 1960s, when health warnings gained prominence. It is very likely that as successive cohorts of smokers are exposed to cigarettes of much lower yield for much greater proportions of their lives, the associated risks will decline even further. However, it is to be emphasized that in all studies, risks of smokers of all types of cigarettes, no matter the yields, were significantly higher than those of lifetime nonsmokers. REFERENCES Benowitz. N.L.. Hall. S.M.. Hernin~. R.I.. Jacob. P.. Jones. R.T. & Osman. A.-L. (1983~ Smokers of low-yield cigarettes do not consume less nicotine. New EngI. J. Med., 309, 139-142 Bross, I.D.J. & Gibson, R. (1968) Risks of lung cancer in smokers who switch to filter cigarettes. Am. J. Public Health, 58, 1396-1403 Hammond, E.C. (1966) Smoking in relation to the death rates of one million men and

208 STELLMAN women. In: Haenszel, W., ed., EpidemioIogic Approaches to the Study of Cancer and Other Chronic Diseases (National Cancer Institute Monograph No. 19), Bethesda, MD, US Department of Health, Education. and Welfare, Public Health Service, National Institutes of Health, National Cancer Institute, pp. 127-204 Hammond, E.C. (1985) Matched group analysis method. In: Garfinkel, L., Ochs, O. & Mushinski, M. , eds, Selection, Follow-up, and Analysis in Prospective Studies: A Workshop (National Cancer Institute Monograph, No. 67; NIH Publication No. 85- 2713), Bethesda, MD, US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute, pp. 15%160 Hammond, E.C., Gaffinkel, L., Seidman, H. & Lew E.A. (1976) "Tar" and nicotine content of cigarette smoke in relation to death rates. Environ. Res., 12, 263-274 Hammond, E.C., Garfinkel, L., Seidman, H. & Eew E.A. (1977) Some recent findings concerning cigarette smoking. In: Hiatt, H.H., Watson, J.D. & Winsten, J.A., eds, Origins of Human Cancer, Book A, Incidence of Cancer in Humans, Cold Spring Harbor, NY, Cold Spring Harbor.Laboratory, pp. 101-112 Higenbottam, T., Shipley, M.J. & Rose, G. (1982) Cigarettes, lung cancer, and coronary heatX disease: the effects of inhalation and tar yield. J. Epidemiol. Community Health, 36, 113-117 Howe, G.R., Burch, J.D,, Miller, A.B., Cook, G.M., Esteve, J., Morrison, B., Gordon, P., Chambers, L.W., Fodor, G. & Winsor, G.M. (1980) Tobacco use, occupation, coffee, various nutrients, and bladder cancer. Y. natl Cancer Inst., 64, 701-713 Kozlowski. L.T., Frecker, R.C., Khouw, V. & Pope, M.A. (1980) The misuse of "less- hazardous" cigarettes and its detection: hole-blocking of ventilated filters. Am. J. Public Health, 70, 1202-1203 Kunze, M. & Vutuc, C. (1980) Threshold of tar exposure: analysis of smoking history of male lung cancer cases and controls. In: Gori, G. & Bock, F.G., eds, A Safe Cigarette? (Banbury Report No. 3), Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, pp. 29-34 Lee, P.N. & Garfinkel, L. (1981) Mortality and type of cigarette smoked. J. Epidemiol. Commun. Health, 35, 16-22 Lubin, J.H., Blot, W.J., Berrino, F., Flamant, R., Gillis, C.R., Kunze, M., Schmahl, D. & Visco, G. (1984a) Patterns of lung cancer risk according to type of cigarette smoked. Int. J. Cancer, 33, 569-576 Lubin, J.H., Blot, W.J., Berrino, F., Flamant, R., Giliis, C.R., Kunze, M., Schmahl, D. & Visco, G. (1984b) Modifying risk of developing lung cancer by changing habits of cigarette smoking. Br. reed. J., 288, 1953-1956 Mushinski, M.H. & Stellman, S.D. (1978) Impact of new smoking trends on women's occupational health. Prey. Med., 7, 349-365 Rimington, J. (1981) The effect of filters on the incidence of lung cancer in cigarette smokers. Environ. Res.. 24, 162-166 btettman, 5.D. (t985) Chairman's remarks on Session V: Data analysis in cohort studies. In: Garfinkel, L., Ochs, O. & Mushinski, M., eds, Selection, Follow-up, and Analysis in Prospective Studies: A Workshop (National Cancer Institute Monograph, No. 67, NIH Publication No. 85-2713), Bethesda, MD, US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Insti- tute, pp. 145-147

CIGARETFE YIELD AND CANCER RISK 209 Stellman, S.D. & Garfinkel, L. (1986) Smoking habits and tar levels in a new American Cancer Society prospective study of 1.2 million men and women. J. natl Cancer Inst. (in press) Vineis, P., Estbve, J. & Terracini, B. (1984) Bladder cancer and smoking in males: types of cigarettes, age at start, effect of stopping and interaction with occupation. Int. J. Cancer, 34, 165-170 Vutuc, C. & Kunze, M. (1982a) Lung cancer risk in women in relation to tar yields of cigarettes. Prey. Med., 11,713-716 Vutuc, C. & Kunze, M. (1982b) Cigarette tar exposure and occupation in female lung cancer patients. Excer_pta reed. Int. Congr., Ser. 55B, 41-48 Vutuc, C. & Kunze, M. (1983) Tar yields of cigarettes and male lung cancer risk. J. natl Cancer Inst., 71, 435-437 Wynder, E.L. & Goldsmith, R. (1977) The epidemiolog2¢ of bladder cancer. A second look. Cancer, 40, 1246-1268 Wynder, E.L. & Hoffmann, D. (1967) Tobacco and Tobacco Smoke. Studies in Experi- mental Carcinogenesis, New York, Academic Press Wynder, E.L. & SteIlman, S.D. (19"~7) Comparative epidemiology of tobacco-related cancers. Cancer Res., 37, 4608-4622 Wynder, E.L & Stellman, S.D. (1979) Impact of long-term filter cigarette usage on lung and larynx cancer risk: a case-control study. J. natl Cancer Inst., 62, 471-477 Wynder, E.L., Mabuchi, K. & Beattie, E.J. (1970) The epidemiology of lung cancer. Recent trends. J. Am. reed. Assoc., 213, 2221-2228 Wynder, E.L., Mushinski, M. & Stellmart, S.D. (1976) The epidemiology of the less harmful cigarette. In: Wynder, E.L., Hoffmann, D. & Gori, G.B., eds, Modifying the Risk for the Smoker. Vol. I. Proceedings of the Third World Conference on Smoking and Health, New York City, June 2-5, 1975, (DHEW Publication No. (NIH) 76-1221), Bethesda, MD, US Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health, National Cancer Institute, pp. 1-12 Wynder, E.L., Goodman, M.T. & Hoffmann, D. (1984) Demographic aspects of the low- yield cigarette: considerations in the evaluation of health risk. J. natl Cancer Inst., 72, 817-822