Abstract

Abstract Importance Statin use has been examined as a potential chemopreventive strategy against colorectal cancer (CRC), with conflicting findings reported. Prior studies have not been able to investigate this topic with adequate follow-up time. Objective To examine prospectively the association between long-term statin use and CRC risk. Design setting and participants The Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) are large prospective cohorts of US women and men. Participants who were alive and free of cancer at the time when information on their statin use was first assessed were eligible for inclusion (100,300 women and 47,991 men), and were followed for up to 26 years (NHS: 1994-2016; HPFS: 1990-2016). Exposures Overall status and duration of statin use. Main outcome and measures Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for exposures and CRC risk. Results We documented 2,924 incident CRC cases during follow-up. In fully-adjusted analyses, compared to participants who never used statins, longer duration of statin use was associated with higher risk of overall CRC (HR, 95%CI was 1.09, 0.98-1.20 for ever use; 1.06, 0.94-1.19 for 1 to 5 years; 1.10, 0.96-1.27 for 6 to 10 years; 1.10, 0.86-1.41 for 11 to 15 years; 1.56, 1.13-2.16 for >15 years; vs. never users, P=.02 for trend). The risk elevation was driven by proximal colon cancer (1.22, 1.05-1.41 for ever use; 1.17, 0.99-1.39 for 1 to 5 years; 1.21, 0.99-1.48 for 6 to 10 years; 1.27, 0.91-1.78 for 11 to 15 years; 2.22, 1.49-3.30 for >15 years; vs. never users, P<.001 for trend) rather than cancers of distal colon or rectum. The results became more robust in sensitivity analyses among participants with hypercholesterolemia. Conclusion and relevance This study does not support benefit of statin use in CRC chemoprevention. Long-term statin use was associated with increased CRC risk (predominantly driven by proximal colon cancer). Citation Format: Yin Zhang, Andrew T. Chan, Jeffrey A. Meyerhardt, Edward L. Giovannucci. Long-term statin use and risk of colorectal cancer: A prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB091.

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