Risk of Bladder Cancer among Male Participants Reporting Nocturia in the Cancer Prevention Study II

Abstract Background: It is believed that contact of the urothelial lining to carcinogens induces mutations that lead to cancer. Nocturia, waking up at night to urinate, may void carcinogens and reduce the risk of bladder cancer. Methods: The Cancer Prevention Study II Nutrition Cohort is a prospective study of cancer incidence that enrolled participants in 1992 with biennial follow-up beginning in 1997. Cases were ascertained through state cancer registry, medical record verification, or death certificate. Cox models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between nocturia and primary incident bladder cancer. Results: Among 49,767 males, 2,655 reported being current smokers in 1997 (30,559 former smokers). There were 1,207 bladder cancers over 210 million person-years of follow-up. Adjusting for demographic and health factors, nocturia once per night was associated with a 46% decreased risk of bladder cancer among smokers (HR1/night, 0.54; 95% CI, 0.30–0.95; HR2+/night, 0.90; 95% CI, 0.52–1.57). We observed no association among nonsmokers (HR1/night, 1.10; 95% CI, 0.72–1.69; HR2+/night, 1.17; 95% CI, 0.75–1.81) or former smokers (HR1/night, 1.17; 95% CI, 0.92–1.49; HR2+/night, 1.12; 95% CI, 0.87–1.43). Our main findings were no longer statistically significant in 2-year (HR, 0.58; 95% CI, 0.31–1.09) and 5-year lag models (HR, 0.80; 95% CI, 0.32–1.99). Conclusions: Only nocturia once per night was associated with a lower risk of bladder cancer in current smokers; however, associations were attenuated in lag analyses and no dose–response relationship was observed. Impact: Nocturia may reduce the risk of bladder cancer among smokers. Further work is needed to confirm findings and understand mechanisms.