Abstract 4943: A prospective study of the association between statin use and the risk of overall and advanced bladder cancer among men

Abstract Background: High cholesterol has been linked to the risk of several cancers, including bladder cancer. Previous research is not consistent as to whether statin medications, which reduce cholesterol levels and have other anti-tumor effects, impact bladder cancer risk. We explored this question in a large prospective cohort study of men, for whom bladder cancer is the fourth leading cause of cancer incidence in the United States. Methods: Our analysis included 44, 116 cancer-free participants of the Health Professionals Follow-Up Study, who were followed for bladder cancer incidence from 1990 through 2018. Statin use was self-reported and updated every two years on questionnaires. Bladder cancer diagnosis was validated with medical or death records. We used multivariable Cox regression to investigate the association between statin use (ever, current, former, and never) and duration of statin use (never, less than 4 years, 4-8 years, and 8 or more years) and the risk of overall bladder cancer, bladder cancer by stage at diagnosis (localized, advanced), and fatal bladder cancer. Models estimating hazard ratios (HR) and 95% confidence intervals (CI) were adjusted for demographic, medical, and lifestyle confounders. Results: During a median of 13.5 years of follow-up, 1, 248 bladder cancers were documented, including 562 advanced and 143 fatal cancers. By mid-way through follow-up, 34% of men reported statin use. In multivariable models, there was a suggestive increased risk of overall bladder cancer comparing current statin users to former or never users (HR 1.13; 95% CI 1.00-1.27), yet no association was observed for localized, advanced, or fatal cancers. Ever use of statins (including former and current use) was not associated with overall, localized, nor advanced bladder cancer, compared to never use. However, there was a suggestive decreased risk of fatal bladder cancer (HR: 0.77; 95% CI 0.58-1.02) among ever users of statins compared to never use. Long-term statin use of 8 or more years was associated with a lower risk of advanced (HR 0.78; 95% CI 0.60-1.00) and fatal bladder cancer (HR 0.59; 95% CI 0.40-0.88), compared to never use. No association was observed for long-term statin use and overall bladder cancer (HR 0.99; 95% CI 0.85-1.16). Conclusion: Results of this study, which investigated overall and clinical subtypes of bladder cancer incidence, suggest that long-term statin use may be protective against the development of advanced and fatal bladder cancer among men. Together with data from clinical trials supporting benefits of statins, this warrants further investigation into whether statins can be used as a preventive tool. Further research is also needed on the potential mechanism by which statins act in bladder carcinogenesis, particularly advanced forms of the disease. Citation Format: Megan R. Shanahan, LeeAnn Lucas, Colleen B. McGrath, Jane B. Vaselkiv, Chaoran Ma, Mark Preston, Edward Giovannucci, Eva Schernhammer, Lorelei A. Mucci. A prospective study of the association between statin use and the risk of overall and advanced bladder cancer among men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4943.