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nil European Journal of Epideraiology 10: 599--604, 1994. © 1994 Kluwer Academic Publishers. Printed in the Netherlands. Bladder cancer and black tobacco cigarette smoking Some results from a French case-control study I. Momast'2, J.P. Daures3, B. Festy2, J. Bontoux4 & F. Gremy: ~ Ddpartement de/'Information Mddicale, H@ital Lapeyronie, Montpellier, France; z Laboratoire d'Hygi~ne et de Santd Publique. Facult~ des Sciences Pharmaceutiques et Biologiques, Paris, France; 3 D~partement de l'Information M~dicale, H@ital Carerneau, N~mes, France; ~ Ddpartement 'Sciences de l'Environnement et Sant~ Publique', Facultd de Pharmacie, Montpellier, France Accepted in revised form 25 July 1994 Abstract. A retrospective study was planned in the H6rault (Mediterranean) region of France where bladder cancer mortality and incidence rates are high. In the present paper, variations in bladder cancer risk according to various smoking-related variables, in particular time of exposure and type of tobacco, are examined. This case-control study with 219 male incident cases and 794 male population controls randomized from electoral rolls was carried out in 1987-89. Trained interviewers obtained information on demographics, dietary habits (coffee, alcohol, arti- ficial sweeteners, vegetables, spices, etc.), occupa- tional exposures and detailed history of tobacco smoking (average number of cigarettes per day, number of years of smoking, age at which they began and/or quitted smoking, use of filter-tip and type of tobacco). The odds ratio (OR) for cigarette smokers versus non-smokers was greater than 5. Results for number of cigarettes daily, duration of smoking and lifetime smoking showed a highly significant dose- response relationship, which was confirmed when these variables were treated as continuous in a • logistic regression model. Eighty-eight percent of the smokers used black tobacco. Quitting smoking did not result in a significant reduction in bladder cancer risk. Higher risks were associated with starting to smoke at an early age (OR before age 13 versus after age 2I = 3.42; 95% CI 1.07-10.9) and with black tobacco smoking (OR black versus blond = 1.63; 95% CI 0.73-3.64). Results suggest that black tobacco may be more harmful than blond tobacco and may have an early non-reversible role in bladder carcinogenesis. Key words: Black tobacco cigarette smoking, Bladder cancer, Case-control study Introduction Cigarette smoking has been clearly shown to increase the risk of developing bladder cancer [1-17]. However the responsible agents and their mecha- nisms of action are unknown. In the Hdranlt (Mediterranear0 Legion of France, where bladder cancer mortality\and incidence rates are high [18, 19], a case-control study was carried out with 219 incident cases and 794 population controls. In the present paper, variations in bladder cancer risk according to various smoking-related variables, in parucular time of exposure and type of tobacco, are examined. These aspects have received relatively little attention in the literature [2, 4, 7, 11, 13]. Materials and methods Case and control selection. Since the sex ratio for bladder cancer is about 1:4 with a higher incidence among men [19], only one male sample was studied. A detailed description of the study design has been reported elsewhere [20, 21]. The cases included in the study consisted of all the French newly-diagnosed cases who had been living in the H6rault district for more than five years and who were diagnosed with a primary, histologically confirmed bladder carci- noma between January 1987 and May 1989. Polyps/ papillomas and recurrences were excluded in order to ensure a more homogeneous population; including papillomas would have resulted in the mixing of two categories of patients: those with papillomas that will change into malignant tumors and those who will never clevelop a cancer. The H6rault Cancer Registry was used to check and to complete the lists of eases identified by urologists. Controls were randomly selected from electoral roils in the whole of the H6rault region. Unfor- tunately, age-matching of cases and controls was not feasible as the electoral rolls were not stratified by age and were not computerized. In order to maximize similarity with the cases, only men over the age of fifty (like the cases) who had been living in This article ~s for individual use only and may not be furlher reproduced or stored declronically without written pem~issina from the copyright holder. Uaauthorized rq~roduc~cm may resuk in fmancial and otfler penalitles. (c) KL~ AC~E~C Pb~L •

600 the H6rault area for more than five years were included. Data collection. Cases were interviewed by two closely supervised interviewers who also contacted the controls listed in the telephone directory and questioned them. Controls not listed in the directory were sent a letter, a questionnaire and a stamped self-addressed envelope. A total of 272 cases were identified, of whom 219 were interviewed; the remaining 53 had died. Among the controls listed in the directory, 558 out of 692 (80.6%) accepted the interview. Among the controls not listed in the directory, 236 out of 329 (71.7%) answered by mail. Of the 227 (22.2%) controls who did not answer, 161 (16.7%) could not be found (death, moved) and 66 (6.5%) refused for the following reasons: old age (11, 16.7%), disease or handicap (II, 16.7%), opposition to sampling prin- ciple (8, 12.1%) or no interest (36, 54.5%). The interview (an average of 25 minutes) was conducted using a structured questionnaire; trained interviewers obtained information on demographics, dietary habits (coffee, alcohol, artificial sweeteners, vegetables, spices, etc.), occupational exposures and a detailed history of tobacco smoking (average number of cigarettes per day, number of years of smoking, age at which they began and/or quitted smoking, use of filter-tip and type of tobacco). For each exposure, starting age, its degree, duration and possible changes were registered. Cigarette smokers were defined as individuals who had smoked at least one cigarette per day for a continuous period of one year or more. Those who smoked predominantly black tobacco (more than 50% of lifetime cigarette use) were regarded as 'black tobacco smokers'. Inhalation was not studied, and people were not asked whether they were 'non-inhalers', 'medium- inhalers' or 'strong inhalers' because, according to' Stepney [22]; there is a very .weak correlation between these subjective responses and the actual measurement of smoke exposure. Only people smoking exclusively cigarettes are considered in this report; cigar and pipe smokers were excluded from the analysis so that any effects detected could not be attributable to other kinds of tObaceo. Statistical analysis. The statistical analysis was done using BMDP soft,,yare. Controls interviewed and those responding by mail have been analysed together as no differences in responses were found between them. Smoking habits were compared, firstly between cases and controls and secondly, between black and blond tobacco smokers using a two-way analysis of variance for quantitative variables and a stratified Mantel-Haenszet procedure for qualitative variables. The effects of smoking on bladder cancer risk were measured by the crude odds ratio and the adjusted odds ratio estimated by the method of maximum likelihood from an unconditional multiple logistic regression [23]. Those variables which showed a significant influence on the risk of bladder cancer when considered alone were included as covariates in this model: age (as a continuous variable), occupational exposure 'at risk' for bladder cancer (oil refinery workers, mechanics, drivers, dyers, plumbers, cooks), square-root of lifetime ground regular coffee consumption (the square-root transformation was used to stabilize variances), square-root of lifetime alcohol consumption (cumu- lative quantity of pure alcohol ingested by men from the different alcoholic beverages they drank), con- sumption, at least "once a week, of vegetables containing provi .t,3min A (courgettes, carrots, spinach, ...), use of boiled olive oil (for cooking and frying), residence for one year or more in a 'non- Mediterranean area of France' (i.e., other than Provenee-Alpes-C6te d'Azur, Languedoc-Roussillon and Corsica), residence for one year or more in a 'Mediterranean country' (i.e., Spain, Italy or North A.friea). Some of these variables were not generally recognized as risk factors for bladder cancer (alcohol consumption, use of boiled olive oil and residence in a Mediterranean country,... ). Nevertheless, they were of considerable importance in this population since they are characteristic aspects of life in the region. The 95% confidence intervals were based on the standard error of coefficient estimates and normal approximation. In some of the analyses presented, comparisons can only be made within the group of subjects who have smoked, because of the need to adjust for smoking variables. The reference category in such analyses is indicated in the tables. Results Sociodemographic characteristics. The distribution of cases and controls by age, education, marital status and place of residence was studied (Table 1). Cases were significantly older and more numerous in urban areas than controls. No significant differences were found for the other demographic variables examined. 88.3% of the smo~kers'eonsumed predominantly black tobacco. No interactions were seen between ease/ control status and type of tobacco used (Table 2). On average, cases smoked more cigarettes daily and smoked for more years than controls. Mean age when starting to smoke, mean years since quitting and proportion of smokers of filter-tipped cigarettes did not differ between cases and controls. Mean age of starting to smoke and proportion of users of filter- tipped cigarettes were significantly lower in black

I i I I I I! II ii Table L Distribution oi demographic variables among cases and controls: bladder cancer case-control study (France - HdraulL 1987-89) Cases Controls Significance (n = 219) (n =.794) p value Age (years) mean 5: standard deviation 67.8 5:9.2 65.3 5:9.3 0.0002 Education (%) primary 88.9 89.0 secondary 8.2 7.8 > 0.05 higher 2.9 3.2 Place of residence (%) urban 82.5 77.0 ntral 17.5 23.0 > 0.05 Marital status (%) single 3.2 3.5 married 88.1 85.3 divorced 1.4 3.5 > 0.05 widowed 7.3 7.7 601 smoker starts smoking the smaller the odds ratio. Nevertheless, this odds ratio remained statistically higher than I. Quitting smoking did not result in a significant reduction in bladder cancer risk. Black tobacco seemed to be more harmful than blond tobacco and filter use did not have any clear protec- tive effect. In the final logistic regression model, including all covariates whether smoking-related or not (Table 4), black tobacco was associated, but not statistically significantly, to a greater risk of bladder cancer than blond tobacco. Smokers presented the same odds ratio of bladder cancer whether they used filters or not. Starting smoking early in life increased signifi- cantly the risk, but no progressive reduction in risk with increased starting age was discernible in the model including this factor in a continuous form. There was no evidence of any significant reduction in risks for ex-smokers, compared to current smokers even for long-term quitters. Discussion than in blond tobacco smokers. No statistically significant differences were observed between these two groups of smokers with respect to the other smoking variables. Analysis of effects of tobacco-related variables. The unadjusted and multivariable adjusted odds ratios for cigarette smokers relative to non-smokers were greater than 5 and were statistically different from 1. Results for daily use of cigarettes, duration of smoking and lifetime smoking (Table 3) showed a highly significant dose-response relationship which is confirmed when these variables arc treated as con- tinuous in a logistic regression model. The later the In this study, the adjusted odds ratio of bladder cancer for smokers versus non-smokers was greater than 5. This is one of the highest figures published so far [1-5, 7-9, 13, 15, 17]. In other Latin countries such as Italy and Spain [7, 13-15] the odds ratio is also higher than that observed in the USA and UK. This difference could be due to the type of tobacco smoked. Black tobacco is quite common in Mediter- ranean countries and relatively uncommon elsewhere. In this French study, among smokers, 93.6% of eases and 86.2% of controls used predominantly black tobacco. Black tobacco appears to be twice as carcinogenic as blond tobacco according to some authors [6, 13, Table 2. Characteristics of cigarette smoking among smokers (cigar and pipe smokers excluded): comparison between cases and controls and between black and blond tobacco smokers: bladder cancer case-control study (France - H&ault, 1987-89) ii II Smokers Type of tobac&~' Cases (n = 159) Controls (n = 399) Significance p value Black Blond Black Blond Cases/ Black/ Interaction (n = 149) (n = I0) (n = 342) (.n = 57) Controls Blond II ,I I Average dail~ dose (cigarettes) 23.0 23.2 20.0 16.2 0.08 > 0.05 > 0.05 ~ ..............¢ ~r~,~td,o ,;n ~ 50.7 a6.3 41.0 0.0002 > 0.05 > 0.05 Average lifetime smoking no cigarettes 341043 313353 262080 190364 0.05 > 0.05 > 0.05 Average starting age of smoking (years) 17.2 19.1 18.3 19.5 > 0.05 0.04 • 0.05 Mean years since 'quitting' (years) 10.4 16.0 10.0 11.0 • 0.05 • 0.05 • 0.05 Use of filter tipb (%) 32.9 60.0 35.1 78.9 • 0.05 < 0.0001 • 0.05 • A black tobacco smoker is a smoker who used more (~ 50%) black than blond tobacco. ~ A filter user is a smoker who smoked more falter-tipped cigarettes (;~ 50%) than cigarettes without any I'tlter.

602 Table 3. Effect of smoking-related variables on risk of bladder cancer for smokers (cigar and pipe smokers excluded) relative to non-smokers: bladder cancer ease-control study (France - H6rault, 1987-89) Cases/ Crude ORt Adjusted 95% CP Coefficient Controls ORn test (p value) Cigarette smoking No 16/237 1.00 1.00 Yes 159/399 5.91 5.27 (2.89-9.60) Daily dose (eigaretms)¢ 0 16/237 1.00 1.00 1-I0 34/135 3.73 3.56 (1.77-7.18) 11-30 89/206 6.40 5.90 (3.13-11.1) > 30 36158 9.19 8.41 (3.98-17.8) Years of smokingc < 1 16/237 1.00 1.00 1-39 17/112 2.25 2.88 (1.22-6.80) 40-55 95/224 6.28 5.25 (2.79-9.87) > 55 47/63 11.05 7.13 (3.34-15.2) Lifetime smoking (no cigarettes)c < 365 16/237 1.00 1.00 365-146000 33/149- 3.28 3.51 (1.75-7.04) 146001-320000 45/133 5.01 4.56 (2.29-9.05) > 320000 81/117 10.25 8.24 (4.31-15.8) Starting age of smoking (years)a Non-smoker 16/237 t.00 1.00 ~ 12 16/9 26.33 20.30 (6.90-59.8) 13-16 52/123 6.26 5.41 (2.75-10.6) 17-20 73/210 5.15 4.86 (2.56-9.23) ~ 21 18/57 4.68 4.60 (2.04-10.4) Years since quitting Non-smoker 16/237 1.00 1.00 ~ 2 65/177 5.44 4.99 (2.57-9.68) 3-15 53/112 7.00 7.05 (3.57-13.9) > 15 411110 5.52 4.56 (2.28-9.12) Type of tobacco" Non-smoker 16/237 1.00 1.00 Blond 10/57 2.60 3.11 (1.25--7.77) Black 149/342 6.45 5.67 (3.10-10.4) Use of filter~ Non-smoker 16/237 1.00 1.00 No 104/234 6.58 5.50 (2.96-10.2) Yes 55/165 4.94 5.13 (2.62-10.0) < 0.0001 < 0.0001 < 0.0001 < 0.0001 • OR: Odds ratio, CI: 95% confidence interval. b Odds ratio adjusted for the eight non smoking-relamd variable, s. c Coefficient test based on logistic regression model with variable in a continuous form. d The coefficient t~st ~ only be applied to smokers (Table 4). ~ A black tobacco smoker is a smoker who used mor~ black (9 50%) than blond tobacco. ~ t A filter user is a smoker who smoked more fdter-tippexl cigarettes (~ 50%) than cigarettes without any filter. 24]. This finding is consistent with experimental data since aromatic amines and nitrosamines are more concentrated in black than blond tobacco smoke [14]. Urinary mutagenieity and levels of 4-atninobiphenyl (a potent human bladder carcinogen) hemoglobin adduets were found to be higher in smokers of black than of blond tobacco [25, 26]. In our study, smokers of black tobacco had a slightly increased risk (although not significant) of bladder cancer relative to smokers of blond tobacco. Thus our data do not fully demonstrate that use of black tobacco itself confers increased risk of bladder cancer. Therefore, either this investigation lacks the power to show such an association or the particular smoking habits of black tobacco users are associated with increased risk. Another explanation, the most likely one, is that

! ! I I I I l II I i I II i ! 1 Table 4. Number of cases and controls, adjusted odds ratios (ORs) and 95 percent confidence estimates (CIs) according to characteristics of cigarette smoking (cigar and pipe smokers excluded): bladder cancer case-control study (France - H6ranlt, 1987-89) Cases/Controls Adjusted OR~'~ 95% CP Coefficient test (p value) Type of tobaccoc Blond 10/57 1.00 Black 149/342 1.63 (0.73--3.64) > 0.05 Filter used - No I04/234 1.00 Yes 55/165 1.00 (0.62-1.63) > 0.05 Starting age of smoking (years)' ~ 21 18/57 1.00 17-20 731210 0.91 (0.46-1.83) 13-16 52/123 0.88 (0.42-1.86) > 0.05 ~ 12 16/9 3.42 (1.07-10.9) Years since quitting smoking' ~ 2 65/177 1.00 3-15 53/i 12 1.48 (0.87-2.50) > 15 41/110 1.14 (0.74--2.69) > 0.05 • OR: Odds ratio, CI: Confidence interval. b For each variable, odds ratios are adjusted for the eight non smoking-related variables, for square-root of lifetime cigarette smoking and for the other three characteristics of smoking. c A black tobacco smoker is a smoker who used more bladk (~ 50%) than blond tobacco. d A filter user is a smoker who smoked more triter-tipped cigarettes (~ 50%) than cigarettes without any falter. " Coefficient test based on logistic regression model with variable in a continuous form. our blond tobacco smokers did not smoke only blond tobacco but were predominantly blond tobacco smokers; they used more blond than black tobacco. Our predominantly black tobacco smokers could also have smoked blond tobacco. So, the difference of toxicity between the two types of tobacco might be obscured. In agreement with most other investigators [2-10, !2, 15-17], a clear dose-response relationship between each of these variables (daily and lifetime cigarette smoking, years of smoking) and bladder cancer risk was found. The increased risk we noted among those who started smoking early in life is only reported by one other author t~..With regard to the number of years since quitting smoking, our findings contrast with those obtained by other researchers [2, 4, 6, 7, 11, 13-15] who underline a reduction in risk among quitters. These temporal aspects of risk may be related to the different stages of carcinogenesis mainly affected by smoking [24, 27, 28]: initiation with agents damaging cellular DNA, promotion with non-genotoxie substances [29]... A decrease in risks along with an increase in the age at which smoking started seems to involve interaction with an early stage while a decrease in risks after exposure stops suggests action at a late" and reversible stage [28]. Our results point towards an early and irre- versible aggression of cigarette smoking in bladder carcinogenesis and are consistent with the hypothesis (probably too simplified) of a different effect of each brand of tobacco: 'initiator' for black tobacco and 'promoter' for blond tobacco [13]. Experimental data corroborate this approach. There are more N- nitrosamines-initiators [30] in smoke from black tobacco [14, 31]. As above-mentioned, the level of 4-aminobiphenyl DNA adducts is found to be higher among black tobacco smokers than among blond tobacco smokers [25, 32]. Similar temporal aspects are also noted in studies concerning exposures to dyes and to 2-naphtylamine, a cancer initiator [33, 34]. Acknowledgements This study was supported by a grant from the Institut National de-In Sant~ et de la Recherche M6dicale (INSERM). The authors thank the following urolo- g_.ist~s: ~Dr Amar, Dr Bringer, Dr Clouye, Dr Constant, Dr Mafissal, Dr Miquel, Prof. Navratil, Dr Rollet. • They also thank Mrs Ferry, Dufort and Ritehie for assistance with the manuscript. References 1. Cartwright RA, Adib R, App!eyard I, Glashan RW, Gray B, Hamilton-Stewart PA, Robinson M, Barbara- Hall D. Cigarette smoking and bladder cancer: An

604 epidemiological inquiry in West Yorkshire. J Epidemiol Community Health 1983; 37: 256-263. 2. Clavel J, Cordier S, Boceon-Gibod L, Hemon D. Tobacco and bladder cancer in males: Increased risk for inhalers and smokers of black tobacco. Int J Cancer 1989; 44: 605-610. 3. Cole P, Monson RP, Haning H, Friedell GH. Smoking and cancer of the lower urinary tract. N Engl J Meal 1971; 284: 129-134. 4. Hartge P, Silverman D, Hoover R, Schairer C, Altman R, Austin D, Cantor K, Child M, Key C, Marrett LD, Mason TJ, Meigs JW, Myers MH, Narayana A, Sullivan JW, Swanson GM, Thomas D, West D. Changing cigarette habits and bladder cancer risk: a case-control study. J Nat Cancer Inst 1987; 78: 1119-1125. 5~ Howe GR, Burch JD, Miller AB, Cook GM, Esteve J, Morrison B, Gordon P, Chambers LW, Fodor G, Winsor GM. Tobacco use, occupation, coffee, various nutrients, and bladder cancer. J Nari Cancer Inst 1980; 64: 701-713. 6. Iseovieh J, Castelletto R, Esteve J, Munoz N, Colanzi R, Coronel A, Deamezola I, Tassi V, Arslan A. Tobacco smoking, occupational exposure and bladder cancer in Argentina. Int J Cancer 1987; 40: 734-740. 7. Lopez-Abente G, Gonzalez GA, Errezola M, Eseolar A, Izarzugaza I, Nebot M, Riboli E. Tobacco smoke inhalation pattern, tobacco type and bladder cancer in Spain. Am J Epidemiol 1991; 134: 830-839. 8. Miller CT, Neutel CI, Nair RC, Marrett LD, Last JM, Collins WE. Relative importance of risk factors in bladder carcinogenesis. J Chron Dis 1978; 31: 51-56. 9. Mommsen S, Aagaard J. Tobacco as a risk factor in bladder cancer. Carcinogenesis 1983; 4: 335-338. 10. Morgan RW, Jain MG. Bladder cancer: smoking, bev- erages and artificial sweeteners. Can Med Assoe J 1974; llh 1067-1069. 11. Morrison AS, Buring JE, Verhoek WG, Aoki K, Leek I, Ohno Y, Obata K. An international study of smoking and bladder cancer. J Urol 1984; 131: 650-654. 12. Rebelakos A, Trichopoulos D, Tzonou A, Zavitsanos X, Velonakis E, Triehopoulos A. Tobacco smoking, coffee drinking, and occupation as risk factors for bladder cancer in Greece. J Nari Cancer Inst 1985; 75: 455-461. 13. Vineis P, Esteve J, Hartge P, Hoover R, Silverman DT, Terraeini B. Effects of timing and type of tobacco in cigarettes-induced bladder cancer. Cancer Res 1988; 48: 3849-3852. 14. Vineis P, Esteve J, Terracird B. Bladder cancer and smoking in males: types of interaction with occupa- tion. Int J Cancer 1984; 34: 165-170. 19. Stoebner A, Daures JP. Le cancer de la vessie dans l'H6rault 1986-1988 - Registre des cancers de l'H6rault. Montpellier (France): Editions P. Fabre 1991. 20. Momas I. Epiddmiologie du cancer de la vessie duns l'H~rault: Enqu&e cas-t~moins. Th~sc de Doctorat de l'Universit6 de Montpellier I, France, 1990. 21. Momas I, Daures JP, Gremy F. Quels t6moins choisir dans une 6tude cas-t6moin? Enqu~te sur le cancer v6sical duns l'H6rault. Rev Epid~m Sant6 Publ 1991; 39: 197-207. 22. Stepney R. Are smokers' self-reports of inhalation a useful measure of smoke exposure? J Epidemiol Community Health 1982; 36: 109-112. 23. Breslow NE, Day NE. Statistical methods in cancer research./-ARC Scientific Publication 32. 1980. Lyon: IARC. 24. Vineis P. Blaek (air-cured) and blond (flue-cured) tobacco and cancer risk, I: Bladder cancer. Eur J Cancer 1991; 27: 1491-1493. 25. Bryant MS, Vineis P, Skipper PL, Tannenbaum SR. Hemoglobin adduets of aromatic amines: Associations with smoking stares and type of tobacco. Proe Nat Acad Sci (Wash) 1988; 85: 9788-9791. 26. Mohtashamipur E, Norpoth K, Lieder F. Urinary excretion of mutagens in smokers of cigarettes with various tar and nicotine yields, black tobacco, and cigars. Cancer Lett 1987; 34: 103-112. 27. Brown C, Chu KC. Use of multistage models to infer stage affected by carcinogenic exposure: Example of lung cancer and cigarette smoking. J Chron Dis 1987; 40(Suppl 2): 171s-179s. 28. Doll R. An epidemiological perspective of the biology of cancer. Cancer Res 1978; 38: 3573-3583. 29. Weinstein B. The origins of human cancer: Molecular mechanisms of carcinogenesis and their applications for cancer prevention and treatment. 27th G.H.A. Howes Memorial Award Lecture. Cancer Res 1988; 48: 4135-4143. 30. Foiles PG, Akerkar SA, Carmella SG. Mass spectro- metric analysis of tobacco-specific nitrosamine-DNA adducts in smokers and nonsmokers. Chem Res Toxicol 1991; 4: 364-368. 31. Cohen SM. Urinary bladder carcinogenesis: Initiation- promotion. Seminars in Ontology 1979; 6: 157-180. 32. Bartsch H, Malaveille C, Friesen M, Kadlubar FF, Vineis P. Black (air-cured) and Blond (flue-cured) tobacco cancer risk, IV: Molecular dosimetry studies implicate aromatic amines as bladder carcinogens. Eur J Cancer 1993; 29A: 1199-1207. 33. Cartwright RA. Occupational bladder cancer cigarette smoking in West Yorkshire. Stand J Work Environ Health 1982; 8(suppl 1): 79-82. Bladder cancer and cigarette smoking in males: A case-control study. Turnoff 1983; 69: 17-22. 16. Wynder EL, Augustine A, Kabat GC. Effect of the type of cigarette smoked on bladder cancer risk. Cancer 1988; 61: 622-627. 17. Wynder EL, Goldsmith RS. The epidemiology of bladder cancer. Cancer 1977; 40: 1246-1268. 18. Rezvani A, Doyon F, Flamant R. Arias de la mortalit~ par cancer en France (1971-1978). Paris (France): Editions INSERM, 1986. of workers exposed to aromatic amines: Analysis of models of carcinogenesis. Br J Cancer 1985; 51: 707-712. Address for correspondence: Dr I. Momas, Laboratoire d'Hygi~ne et de Sant6 Publique, Facult6 des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observa- toire F-75 270 Pads, France Phone: (1) 43 29 12 08, ext. 227 ! I I I I I I [ ! ! I ! ! [ I