Unveiling an Association between Waterpipe Smoking and Bladder Cancer Risk: A Multicenter Case-Control Study in Iran

Background: Limited data exist for the association between bladder cancers and waterpipe smoking, an emerging global public health concern. Methods: We used the IROPICAN database in Iran and employed multivariable logistic regression, adjusting for cigarette smoking, opium use, and other confounding factors. In addition, we studied the association between exclusive waterpipe smoking and bladder cancer. Results: We analyzed 717 cases and 3477 controls and a subset of 215 patients and 2145 controls who did not use opium or cigarettes. Although the OR adjusted for opium, cigarettes, and other tobacco products was 0.92 (95% CI: 0.69, 1.20), we observed a statistically significant elevated risk in exclusive waterpipe smokers (OR=1.78, 95% CI 1.16, 2.72) compared to non-users of opium or any tobacco. Associations were strongest for smoking more than two heads/day (OR=2.25, 95% CI: 1.21, 4.18) and for initiating waterpipe smoking at an age less than 20 (OR=2.73, 95% CI 1.11, 6.72). The OR for urothelial bladder cancer was higher in ex-smokers (OR=2.35, 95% CI 1.24-4.42) than in current smokers (OR=1.52, 95% CI 0.72-3.15). All observed associations were consistently higher for urothelial histology. Conclusions: Waterpipe smoking may be associated with an increased risk of bladder cancer, notably among individuals who are not exposed to cigarette smoking and opium. Impact: The study provides compelling evidence that waterpipe smoking is a confirmed human carcinogen, demanding action from policymakers.