Modification of the association between daily aspirin use and ovarian cancer risk by potentially modifiable risk factors.

Abstract Purpose: Daily aspirin use has been associated with a 10-20% reduced risk of ovarian cancer in case-control and cohort studies. However, it is unknown whether certain subgroups of women are more likely to benefit from potential chemoprevention through daily aspirin. We determined whether the association between aspirin use and ovarian cancer varies by other ovarian cancer risk factors, including age, body mass index (BMI), duration of oral contraceptive use, and duration of menopausal hormone use. Methods: This study included women from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. Women were enrolled between 1993-2001 and followed for cancer outcomes through 2009. Aspirin use and ovarian cancer risk factors were reported at baseline. Cox proportional hazards regression was used to examine associations between daily aspirin use and ovarian cancer risk. Analyses were conducted overall and stratified by baseline age (50-59, 60-69, ≥70), BMI (<25, 25-29, ≥30 kg/m2), duration of oral contraceptive use (none, ≤5 years, >5 years of use), and duration of menopausal hormone use (none, ≤5 years, >5 years of use). All models were adjusted for these risk factors, as well as race (white, non-white), study arm (intervention, control), and number of live births (0, 1, 2, 3, ≥4). Statistical interaction was tested via likelihood ratio tests. Results: There were 60,713 women included in this study, of whom 364 developed epithelial ovarian cancer. Overall, compared to nonuse or infrequent use, a reduced risk of ovarian cancer was suggested with daily aspirin use (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.61-1.03). The association appeared stronger among women with BMI ≥30 kg/m2 (HR: 0.61, 95% CI: 0.36-1.13) compared to women with BMI <25 kg/m2 (HR: 0.95, 95% CI: 0.64-1.41) or 25-29 kg/m2 (HR: 0.87, 95% CI: 0.55-1.38, p-interaction=0.48). The association remained inverse and did not vary quantitatively or statistically by baseline age (p-interaction=0.96), duration of oral contraceptive use (p-interaction=0.85), or duration of menopausal hormone use (p-interaction=0.95). Conclusion: Consistent with prior studies, women who used daily aspirin had a lower risk of developing ovarian cancer. The association was not modified by other ovarian cancer risk factors, with the possible exception of BMI. We plan to similarly evaluate modification of the associations between aspirin use and risk of other cancers with potential inflammatory etiologies (e.g., colorectal) and will evaluate this in multiple cohorts. To determine whether aspirin is an effective form of chemoprevention in certain subgroups, ongoing research will likely need to pool data across studies or leverage other large-scale resources. Citation Format: Lauren M. Hurwitz, Kara A. Michels, Britton Trabert. Modification of the association between daily aspirin use and ovarian cancer risk by potentially modifiable risk factors [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr A02.