Evaluation of statin use and renal cell carcinoma risk identifies sex-specific associations with RCC subtypes

Abstract

Background: The association between statin use and risk of renal cell carcinoma (RCC) has been debated. We aimed to evaluate whether statin use is associated with RCC risk.

Material and methods: We studied 100,195 women in the Nurses’ Health Study (NHS) from 1994 to 2016; 91,427 women in the Nurses’ Health Study II (NHS II) from 1999 to 2015; and 45,433 men in the Health Professionals Follow-up Study (HPFS) from 1990 to 2016. Statins and covariate data were collected at baseline and then biennially. Outcome was measured as incidence of total RCC and clinically relevant disease subgroups. Cox proportional hazards models estimated covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: During follow-up, 661 participants developed RCC. There was no significant association between the use of statins and the risk of overall RCC, fatal RCC, or advanced or localized disease. Across cohorts, the adjusted HR for ever vs. never users was 0.97 (95% CI 0.81–1.16). Female ever users of statins were at increased risk of high-grade disease in the NHS only (HR 1.75, 95% CI 1.07–2.85). Among men only, ≥4 years of statin use was associated with an increased risk of clear cell RCC (HR 1.65, 95% CI 1.10–2.47).

Conclusions: Statin use was not associated with the overall risk of RCC. However, it was associated with an increased risk of high-grade disease among women in the NHS cohort and an increased risk of clear cell RCC among men. The reasons for these inconsistent results by sex are unclear.

Keywords:

• Kidney neoplasms
• renal cell carcinoma
• hydroxymethylglutaryl-CoA reductase inhibitors

Acknowledgements

We are grateful to Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA. We would also like to thank the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by funding from the National Institutes of Health [UM1 CA186107, P01 CA87969, U01 CA176726, U01 CA167552]. REG is a Prostate Cancer Foundation Young Investigator. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.