BARBITURATES, SMOKING, AND BLADDER-CANCER RISK

Phenobarbital treatment has been observed to be negatively associated with bladder cancer risk in a few studies. It has been suggested that phenobarbital may induce drug-metabolizing enzymes that detoxify the b ladder carcinogens found in cigarette smoke. We examined the relations hip of barbiturate use to bladder cancer risk and the potential modify ing effect of cigarette smoking in a large cohort of Kaiser Permanente Medical Care Program members with computerized pharmacy prescriptions and smoking information. Newly diagnosed bladder cancers were identif ied among individuals in the study cohort by linkage with data from ca ncer registries. The overall standardized incidence ratio associated w ith barbiturate use was 0.71 [95% confidence interval (CT), 0.51-0.99] , Among current smokers, former smokers, and never smokers, the standa rdized incidence ratios were 0.56 (95% CI, 0.23-1.16), 0.68 (95% CI, 0 .27-1.40), and 1.04 (95% CI, 0.48-1.98), respectively. Although our es timates were imprecise, the finding of an inverse association between barbiturate treatment and bladder cancer risk only among current and f ormer cigarette smokers is consistent with the hypothesis that treatme nt with these medications induces drug-metabolizing enzymes that deact ivate bladder carcinogens found in cigarette smoke.