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Statin use, hyperlipidemia, and risk of glioma

Abstract

Background Statins have previously been shown to have protective effects for other cancers, but no prospective studies of statin use and glioma have been conducted. Methods We evaluated the association between statin use and risk of glioma in the female Nurses’ Health Study (NHS, n = 114,419) and Nurses’ Health Study II (NHSII, n = 115,813) and the male Health Professionals Follow-up Study (HPFS, n = 50,223). Glioma cases were confirmed by medical record review. Age and multivariable-adjusted hazard ratios of glioma by statin use were estimated using Cox proportional hazards models. Results In 4,430,700 person-years of follow-up, we confirmed 483 incident cases of glioma. Compared with never-users, ever statin use was associated with borderline increased risk of glioma in the combined cohorts (age-adjusted HR = 1.23, 95% CI 0.99–1.54), as was longer duration of statin use (HR = 1.48, 95% CI 1.08–2.03 comparing > 8 years of use to never use, p-trend = 0.01). We also observed a significant inverse association between hyperlipidemia and glioma in multivariable models (HR = 0.74, 95% CI 0.59–0.93 in combined cohorts), which was attenuated in lagged analyses. Compared to never use, in multivariable-adjusted models, ever statin use (HR = 1.43, 95% CI 1.10–1.86) and statin use duration (HR = 1.72, 95% CI 1.21–2.45, for > 8 years of use, p-trend = 0.003) were each significantly associated with increased glioma risk. Conclusion In contrast to case–control studies reporting inverse associations, we found borderline increased risk of glioma with statin use. Results were strengthened after adjustment for cardiovascular risk factors due to an unexpected inverse association between hyperlipidemia and glioma risk. Further studies of statin use, hyperlipidemia, and glioma risk are warranted.

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Acknowledgements

We would like to thank the participants and staff of the Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow Up Study for their valuable contributions as well as 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.

Funding

National Institutes of Health (NIH) PO1 CA87969, U01 CA167552, UM1 CA186107, UM1 CA176726, UM1 CA167552, T32 CA009001 (DJC), F30 CA235791 (DJC).

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Correspondence to David J. Cote.

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Cote, D.J., Rosner, B.A., Smith-Warner, S.A. et al. Statin use, hyperlipidemia, and risk of glioma. Eur J Epidemiol 34, 997–1011 (2019). https://doi.org/10.1007/s10654-019-00565-8

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Keywords

  • Statin
  • Epidemiology
  • Glioblastoma multiforme
  • Glioma
  • Incidence