Int. J . Cancer: 47, 207-212 (1991) 0 1991 Wiley-Liss, Inc.
Publication of the International Union Against Cancer Publication de I'Union Internattonale Contre le Cancer
COFFEE CONSUMPTION AND BLADDER CANCER RISK 3. CLAVELand S. CORDIER Institut National de la Sante' et de la Recherche Midicale, Unite' 170, 16, av. Paul Vaillant-Couturier-94807-Villejuif Cedex, France. The relationship between coffee drinking and the risk of bladder cancer was analyzed within the framework of a French hospital-based case-control study conducted between 1984 and 1987, which included 690 cases of histologically confirmed bladder cancer (599 males and 91 females), and 690 age-, sex- and hospital-matched controls. To dissociate the effects of smoking and coffee drinking among males, the analysis of the male group was restricted to 2 contrasted rubgroups: non-smokers on the one hand, and current smokers and inhalers of black tobacco cigarettes on the other. Coffee drinking was found to be significantly associated with the risk of bladder cancer among men in both groups and the increase in the risk was dose-dependent (OR = I, 2.9, 5. I respectively, for drinking I, 2, 3 3 cups of coffee per day among nonsmokers, and I, 2.5 and 3.0 respectively,for drinking 14.5-7, >7 cups among smokers). This result was not observed for women.
Although a possible association between coffee consumption and the incidence of bladder cancer has been repeatedly examined, there is no clear evidence for or against the existence of such an association. When a statistically significant relationship was found, an estimated relative risk (RR) of about 1.5 for coffee drinkers compared to non-drinkers has generally been proposed (Cole, 1971; Fraumeni et al., 1971; Miller, 1977; Mettlin and Graham, 1979; Howe et al., 1980; Hartge et al., 1983; Rebelakos et al., 1985; Jensen et al., 1986; Claude et al., 1986; Risch et al., 1988). In the work of Cole (1971) and Risch et al. (1988), the risk concerned women only, and in that of Fraumeni et al. (1971), Blacks. No relationship between coffee drinking and the risk of bladder cancer has been found in other studies [Morgan and Jain, 1974; Gonzales etal., 1985; Cartwright et al., 1981; Najem et al., 1982; Morrison et al., 1982; Marett etal., 1983; Kabat etal., 1986; Mommsenetal., 1983 (in women)]. Most studies emphasized the strong association between smoking and coffee drinking, which may obscure the relationship between coffee consumption and the risk of bladder cancer. However, Iscovich et al. (1987) reported a clear dosedependent relationship, with an RR of 12 for drinkers of more than 3 cups of coffee per day even though smoking was taken into account in the analysis. When analysis was restricted to non-smokers, Ciccone and Vineis (1988) also found a clear dose-dependent relation between coffee consumption and the risk of bladder cancer among non-smoking males, and Hartge et al. (1983) in a large-scale survey, found an RR of 4.2 for heavy coffee drinkers (>49 cups/wk) vs. light drinkers. In a few studies, more precise data on the type of coffee (usual, instant, caffeinated or decaffeinated) were available (Howe et al., 1980; Cartwright et al., 1981; Hartge et al., 1983; Marett et al., 1983; Jensen et al., 1986; Kabat et al., 1986; Risch et al., 1988). No excess risk was associated with the consumption of either decaffeinated or instant coffee. Some mutagens are found in both coffee and tea (Nagao et al., 1979). Jensen et al. (1986) reported an association between the risk of bladder cancer and tea consumption, for drinkers of more than 500 ml tea per day, and Slattery et al. (1 988) found a similar association in non-smoking teadrinkers, with a dose-dependent relation. However, neither Howe et al. (1980) nor Risch et al. (1988) observed such a relationship.
Since coffee drinking may be involved in the risk of bladder cancer, this association was analyzed within the framework of a large case-control survey on occupational risk factors in which smoking parameters were accurately recorded. MATERIAL AND METHODS
The present data were supplied by a hospital-based casecontrol survey on occupational risk factors of bladder cancer, conducted in 7 French centers between 1984 and 1987. Cases and controls The survey included 1,198 men (599 cases and 599 controls) and 182 women (91 cases and 91 controls). Cases were patients below 80, with histologically confirmed bladder cancer. Most of them, (418 men, 68.9%, and 63 women, 69.2%), were included in our survey during the year following diagnosis. Histologic grade was undetermined for 58 men (9.8%) and 8 women (8.8%). There was no infiltration in 68.9% and 72.5% of the men and women, respectively. The controls were patients admitted to the same hospitals as the cases for causes other than cancer and respiratory diseases (because of the possible association between the latter diseases and the occupational exposures surveyed), and with no symptom suggestive of bladder cancer. They were also matched with cases for sex, age ( 2 5 years), and place of residence (inside or outside the main catchment area of the hospital). Interviews Interviews were based on a standard questionnaire and included questions about demographic characteristics, occupational history, smoking habits, and beverage consumption. With regard to the latter, patients were asked about their daily consumption of tea and coffee (usual, instant, caffeinated or decaffeinated) since the age of 18, and about any changes which had occurred in their habits. Average daily individual consumption was therefore calculated from 18 years to age at diagnosis (which was, for controls, their age at the diagnosis of their corresponding case). Time-related variables such as age at the start of tea or coffee consumption, and duration of consumption, were not available. Most controls were hospitalized for chronic conditions which might have led to changes in their coffee consumption habits even a long time before hospitalization. To reduce the influence of recent changes, we considered life-time consumption of coffee from the age of 18 up to 10 years before diagnosis, assuming a latency time of at least 10 years. However, coffee consumption calculated up to diagnosis was closely correlated to coffee consumption calculated up to 10 years before diagnosis.
Statistical analysis To control the effect of smoking, separate analyses were carried out for smokers and non-smokers, using logistic regresReceived: July 19, 1990 and in revised form September 10, 1990
208
CLAVEL AN D CORDIER
sion models. The models were tested by the likelihood ratio method. In the multivariate analyses, the Chi-square values for trend tests were computed as the likelihood ratios between the models with and without the variable of interest, coded as a single variable taking as values the mean values of the classes. All the models included the matching variables age, hospital, and area of residence. Smoking parameters used for adjustment were, as required, class of smoker (current, former or non-smoker), or the set of parameters which, in a previous analysis of the same data, were shown to be involved in the risk of bladder cancer (Clavel et al., 1989): inhaling (yesino), type of tobacco (blacklblond), average cigarette consumption ( 0.05.
the males, first, with no adjustment for smoking, and then with a simple adjustment (Table 111). Without adjustment, coffee drinking was found to be significantly associated with the risk of bladder cancer, and the relationship was dose-dependent. When the same analysis was performed with a simple adjustment for smoking status ( i . e . , non-smoker, former smoker or current smoker), the relationship was weaker, but the trend was still significant. Last, in an analysis performed among smokers (Table 111) and adjusted for all the parameters involved in the relationship between smoking and the risk of bladder cancer, no relationship was observed. Attempts to estimate the risk of bladder cancer associated with coffee drinking among smokers proved to be difficult. The omission of significant parameters of smoking might have led to underadjustment for smoking (Savitz and Baron, 1988). Conversely, when all smoking parameters identified earlier as components of the risk of bladder cancer were included in the logistic model, the estimates of the risk associated with coffee drinking were liable to be distorted if the model did not exactly fit the data with respect to each smoking parameter. To overcome these problems, we estimated the risk associated with coffee drinking among 2 contrasted smoking categories: non-smokers, and current smokers and inhalers of black tobacco cigarettes. The latter group, in which the variation in risk associated with smoking was clearly reduced, provided better conditions for observing the variations in the risk associated with coffee consumption. In addition, average daily cigarette consumption and total duration of smoking were included in the logistic model. In these 2 categories, the relationship between coffee drinking and the risk of bladder cancer was statistically significant, and the odds ratio increased with the number of cups of coffee consumed (Table IV). However, the slope of the increased OR was higher for non-smokers than for smokers. Table V reports the analysis concerning females. The numbers being small, all female smokers were considered together. No significant association of the risk of bladder cancer with coffee drinking was found among women either in smokers, or in non-smokers (Table V). Special types of coffee As there were very few drinkers of instant or decaffeinated coffee, we were unable to estimate the specific effects of these beverages on the risk of bladder cancer.
Tea (Tables W and VII) The number of tea drinkers was small, and most of them only drank one cup per day. Among female smokers, tea con-
COFFEE DRINKING A N D BLADDER CANCER
209
TABLE 111- ESTIMATED ODDS RATIOS (OR) FOR RELATIONSHIP BETWEEN AVERAGE DAlLY CONSUMPTION OF COFFEE AND RISK OF BLADDER CANCER IN MALES, IN DIFFERENT CONDITIONS WITH RESPECT TO THE ADJUSTMENT FOR SMOKING
Cases
Controls
OR'
C195%
Average daily consumption of coffee (Number of cups per day) All subjects Before adjustment for smoking parameters 0 12 20 1 .oo 1-4 488 51 1 1.45 0.69- 3.03 5-1 61 52 1.95 0.86- 4.45 >7 27 10 3.77 1.33-10.61 unknown 11 6 Total 599 599 After adjustment for smoker status (non-smoker, former smoker, current smoker) 0 12 20 1 .oo 1-4 488 51 1 1.24 0.56-2.74 5-7 61 52 1.46 0.60-3.5 1 >7 21 10 2.94 1.06-8.15 unknown 11 6 Total 599 599 Cigarette smokers Before adjustment for smoking parameters 0 10 9 1 .oo 1-4 445 39 1 0.98 0.39-2.46 5-7 59 43 1.24 0.46-5.31 >7 24 8 2.19 0.64-7.43 unknown 8 6 Total 546 451 After adjustment for all smoking parameters3 7 24 unknown 8 6 Total 546 451
PZ
0.02
(***I
ns
(**I
ns
(*I
ns (ns)
'OR are adjusted for matching variables (age, hospital and place of residence).-2p value for Chi square of likelihood ratio; ns: p > 0.05; in parentheses: p value for trend test ***
Publication of the International Union Against Cancer Publication de I'Union Internattonale Contre le Cancer
COFFEE CONSUMPTION AND BLADDER CANCER RISK 3. CLAVELand S. CORDIER Institut National de la Sante' et de la Recherche Midicale, Unite' 170, 16, av. Paul Vaillant-Couturier-94807-Villejuif Cedex, France. The relationship between coffee drinking and the risk of bladder cancer was analyzed within the framework of a French hospital-based case-control study conducted between 1984 and 1987, which included 690 cases of histologically confirmed bladder cancer (599 males and 91 females), and 690 age-, sex- and hospital-matched controls. To dissociate the effects of smoking and coffee drinking among males, the analysis of the male group was restricted to 2 contrasted rubgroups: non-smokers on the one hand, and current smokers and inhalers of black tobacco cigarettes on the other. Coffee drinking was found to be significantly associated with the risk of bladder cancer among men in both groups and the increase in the risk was dose-dependent (OR = I, 2.9, 5. I respectively, for drinking I, 2, 3 3 cups of coffee per day among nonsmokers, and I, 2.5 and 3.0 respectively,for drinking 14.5-7, >7 cups among smokers). This result was not observed for women.
Although a possible association between coffee consumption and the incidence of bladder cancer has been repeatedly examined, there is no clear evidence for or against the existence of such an association. When a statistically significant relationship was found, an estimated relative risk (RR) of about 1.5 for coffee drinkers compared to non-drinkers has generally been proposed (Cole, 1971; Fraumeni et al., 1971; Miller, 1977; Mettlin and Graham, 1979; Howe et al., 1980; Hartge et al., 1983; Rebelakos et al., 1985; Jensen et al., 1986; Claude et al., 1986; Risch et al., 1988). In the work of Cole (1971) and Risch et al. (1988), the risk concerned women only, and in that of Fraumeni et al. (1971), Blacks. No relationship between coffee drinking and the risk of bladder cancer has been found in other studies [Morgan and Jain, 1974; Gonzales etal., 1985; Cartwright et al., 1981; Najem et al., 1982; Morrison et al., 1982; Marett etal., 1983; Kabat etal., 1986; Mommsenetal., 1983 (in women)]. Most studies emphasized the strong association between smoking and coffee drinking, which may obscure the relationship between coffee consumption and the risk of bladder cancer. However, Iscovich et al. (1987) reported a clear dosedependent relationship, with an RR of 12 for drinkers of more than 3 cups of coffee per day even though smoking was taken into account in the analysis. When analysis was restricted to non-smokers, Ciccone and Vineis (1988) also found a clear dose-dependent relation between coffee consumption and the risk of bladder cancer among non-smoking males, and Hartge et al. (1983) in a large-scale survey, found an RR of 4.2 for heavy coffee drinkers (>49 cups/wk) vs. light drinkers. In a few studies, more precise data on the type of coffee (usual, instant, caffeinated or decaffeinated) were available (Howe et al., 1980; Cartwright et al., 1981; Hartge et al., 1983; Marett et al., 1983; Jensen et al., 1986; Kabat et al., 1986; Risch et al., 1988). No excess risk was associated with the consumption of either decaffeinated or instant coffee. Some mutagens are found in both coffee and tea (Nagao et al., 1979). Jensen et al. (1986) reported an association between the risk of bladder cancer and tea consumption, for drinkers of more than 500 ml tea per day, and Slattery et al. (1 988) found a similar association in non-smoking teadrinkers, with a dose-dependent relation. However, neither Howe et al. (1980) nor Risch et al. (1988) observed such a relationship.
Since coffee drinking may be involved in the risk of bladder cancer, this association was analyzed within the framework of a large case-control survey on occupational risk factors in which smoking parameters were accurately recorded. MATERIAL AND METHODS
The present data were supplied by a hospital-based casecontrol survey on occupational risk factors of bladder cancer, conducted in 7 French centers between 1984 and 1987. Cases and controls The survey included 1,198 men (599 cases and 599 controls) and 182 women (91 cases and 91 controls). Cases were patients below 80, with histologically confirmed bladder cancer. Most of them, (418 men, 68.9%, and 63 women, 69.2%), were included in our survey during the year following diagnosis. Histologic grade was undetermined for 58 men (9.8%) and 8 women (8.8%). There was no infiltration in 68.9% and 72.5% of the men and women, respectively. The controls were patients admitted to the same hospitals as the cases for causes other than cancer and respiratory diseases (because of the possible association between the latter diseases and the occupational exposures surveyed), and with no symptom suggestive of bladder cancer. They were also matched with cases for sex, age ( 2 5 years), and place of residence (inside or outside the main catchment area of the hospital). Interviews Interviews were based on a standard questionnaire and included questions about demographic characteristics, occupational history, smoking habits, and beverage consumption. With regard to the latter, patients were asked about their daily consumption of tea and coffee (usual, instant, caffeinated or decaffeinated) since the age of 18, and about any changes which had occurred in their habits. Average daily individual consumption was therefore calculated from 18 years to age at diagnosis (which was, for controls, their age at the diagnosis of their corresponding case). Time-related variables such as age at the start of tea or coffee consumption, and duration of consumption, were not available. Most controls were hospitalized for chronic conditions which might have led to changes in their coffee consumption habits even a long time before hospitalization. To reduce the influence of recent changes, we considered life-time consumption of coffee from the age of 18 up to 10 years before diagnosis, assuming a latency time of at least 10 years. However, coffee consumption calculated up to diagnosis was closely correlated to coffee consumption calculated up to 10 years before diagnosis.
Statistical analysis To control the effect of smoking, separate analyses were carried out for smokers and non-smokers, using logistic regresReceived: July 19, 1990 and in revised form September 10, 1990
208
CLAVEL AN D CORDIER
sion models. The models were tested by the likelihood ratio method. In the multivariate analyses, the Chi-square values for trend tests were computed as the likelihood ratios between the models with and without the variable of interest, coded as a single variable taking as values the mean values of the classes. All the models included the matching variables age, hospital, and area of residence. Smoking parameters used for adjustment were, as required, class of smoker (current, former or non-smoker), or the set of parameters which, in a previous analysis of the same data, were shown to be involved in the risk of bladder cancer (Clavel et al., 1989): inhaling (yesino), type of tobacco (blacklblond), average cigarette consumption ( 0.05.
the males, first, with no adjustment for smoking, and then with a simple adjustment (Table 111). Without adjustment, coffee drinking was found to be significantly associated with the risk of bladder cancer, and the relationship was dose-dependent. When the same analysis was performed with a simple adjustment for smoking status ( i . e . , non-smoker, former smoker or current smoker), the relationship was weaker, but the trend was still significant. Last, in an analysis performed among smokers (Table 111) and adjusted for all the parameters involved in the relationship between smoking and the risk of bladder cancer, no relationship was observed. Attempts to estimate the risk of bladder cancer associated with coffee drinking among smokers proved to be difficult. The omission of significant parameters of smoking might have led to underadjustment for smoking (Savitz and Baron, 1988). Conversely, when all smoking parameters identified earlier as components of the risk of bladder cancer were included in the logistic model, the estimates of the risk associated with coffee drinking were liable to be distorted if the model did not exactly fit the data with respect to each smoking parameter. To overcome these problems, we estimated the risk associated with coffee drinking among 2 contrasted smoking categories: non-smokers, and current smokers and inhalers of black tobacco cigarettes. The latter group, in which the variation in risk associated with smoking was clearly reduced, provided better conditions for observing the variations in the risk associated with coffee consumption. In addition, average daily cigarette consumption and total duration of smoking were included in the logistic model. In these 2 categories, the relationship between coffee drinking and the risk of bladder cancer was statistically significant, and the odds ratio increased with the number of cups of coffee consumed (Table IV). However, the slope of the increased OR was higher for non-smokers than for smokers. Table V reports the analysis concerning females. The numbers being small, all female smokers were considered together. No significant association of the risk of bladder cancer with coffee drinking was found among women either in smokers, or in non-smokers (Table V). Special types of coffee As there were very few drinkers of instant or decaffeinated coffee, we were unable to estimate the specific effects of these beverages on the risk of bladder cancer.
Tea (Tables W and VII) The number of tea drinkers was small, and most of them only drank one cup per day. Among female smokers, tea con-
COFFEE DRINKING A N D BLADDER CANCER
209
TABLE 111- ESTIMATED ODDS RATIOS (OR) FOR RELATIONSHIP BETWEEN AVERAGE DAlLY CONSUMPTION OF COFFEE AND RISK OF BLADDER CANCER IN MALES, IN DIFFERENT CONDITIONS WITH RESPECT TO THE ADJUSTMENT FOR SMOKING
Cases
Controls
OR'
C195%
Average daily consumption of coffee (Number of cups per day) All subjects Before adjustment for smoking parameters 0 12 20 1 .oo 1-4 488 51 1 1.45 0.69- 3.03 5-1 61 52 1.95 0.86- 4.45 >7 27 10 3.77 1.33-10.61 unknown 11 6 Total 599 599 After adjustment for smoker status (non-smoker, former smoker, current smoker) 0 12 20 1 .oo 1-4 488 51 1 1.24 0.56-2.74 5-7 61 52 1.46 0.60-3.5 1 >7 21 10 2.94 1.06-8.15 unknown 11 6 Total 599 599 Cigarette smokers Before adjustment for smoking parameters 0 10 9 1 .oo 1-4 445 39 1 0.98 0.39-2.46 5-7 59 43 1.24 0.46-5.31 >7 24 8 2.19 0.64-7.43 unknown 8 6 Total 546 451 After adjustment for all smoking parameters3 7 24 unknown 8 6 Total 546 451
PZ
0.02
(***I
ns
(**I
ns
(*I
ns (ns)
'OR are adjusted for matching variables (age, hospital and place of residence).-2p value for Chi square of likelihood ratio; ns: p > 0.05; in parentheses: p value for trend test ***
