Purpose: Daily low-dose aspirin is recommended for certain individuals for prevention of cardiovascular disease and colorectal cancer. However, there are known risks associated with aspirin use. Identifying subgroups of individuals most likely to benefit from aspirin for cancer prevention would help to tailor risk-benefit calculations to maximize benefits and minimize risks. We investigated whether associations between daily aspirin use and risk of several cancers vary by other cancer risk factors, including age, body mass index (BMI), smoking status, physical inactivity, and family history of cancer.

Methods: We pooled 423,495 individuals from two prospective, U.S.-based studies: the NIH-AARP Diet and Health Study (1995-2011), a population-based cohort study, and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2009), a multicenter randomized controlled trial. Daily aspirin use was self-reported at baseline and defined as use ≥5 days/week. Our main outcome measures were incident colorectal, ovarian, breast, endometrial, and aggressive prostate cancers. We used multivariable Cox proportional hazards regression to examine associations between daily aspirin use and risk of each cancer, overall and across strata of risk factors.

Results: Compared with non-use and non-daily use, daily aspirin use was associated with a 15% reduction in colorectal cancer risk (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.80-0.89). Risk reductions were generally consistent across strata of other risk factors but attenuated with increasing BMI (p-interaction=0.16). For ovarian cancer, there was no significant association overall (HR: 0.93, 95% CI: 0.80-1.08) but a reduced risk among obese women (HR: 0.73, 95% CI: 0.52-0.98, p-interaction=0.12). We observed suggestive modest risk reductions for breast (HR: 0.96, 95% CI: 0.91-1.00) and aggressive prostate (HR: 0.95, 95% CI: 0.90-1.00) cancer and a null association for endometrial cancer (HR: 0.96, 95% CI: 0.86-1.07), with no strong effect modification observed.

Conclusions: Daily aspirin use was associated with reduced colorectal cancer risk across strata of cancer risk factors. The magnitude of the benefit varied by BMI for colorectal cancer and was restricted to obese women for ovarian cancer. The potential modifying effect of BMI warrants further investigation and may need to be considered in risk-benefit calculations for aspirin use.

Citation Format: Lauren M. Hurwitz, Kara A. Michels, Michael B. Cook, Ruth M. Pfeiffer, Britton Trabert. Associations between daily aspirin use and cancer risk across strata of major cancer risk factors in two large U.S. cohorts [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4667.