ASPO Abstracts
Does polygenic risk score modify the association between frequent aspirin use and ovarian cancer risk? An analysis within the Ovarian Cancer Association Consortium (OCAC)
Category: Lifestyles Behavior, Energy Balance & Chemoprevention
Conference Year: 2022
Abstract Body:
Purpose: Frequent aspirin use is associated with reduced epithelial ovarian cancer risk, but it is unknown whether genetic factors modify this association. To inform potential strategies for precision prevention, we examined whether the association between frequent aspirin use and ovarian cancer risk is modified by an ovarian cancer polygenic risk score in the Ovarian Cancer Association Consortium (OCAC).Methods: We pooled data from OCAC case-control studies with data on frequent aspirin use (‚â•6 days per week). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between frequent aspirin use and ovarian cancer, adjusted for age, number of full-term births, oral contraception use duration, menopausal hormone therapy use duration, body mass index, and study. Analyses were stratified by quartile of the polygenic risk score, which was previously developed within OCAC, and the likelihood ratio test was used to test for interaction. Polytomous logistic regression was used to explore associations by ovarian cancer histotype.Results: There were 4,738 epithelial ovarian cancer cases and 6,694 controls from eight studies included in this analysis. Though frequent aspirin use was associated with reduced ovarian cancer risk overall (OR: 0.87, 95% CI: 0.77-0.98), the polygenic risk score appeared to modify this association (p-interaction=0.03). Specifically, there was no association among women in the first (OR: 1.04, 95% CI: 0.68-1.58) or second (OR: 1.10, 95% CI: 0.81-1.49) quartile of the polygenic risk score, a protective association among women in the third quartile (OR: 0.69, 95% CI: 0.54-0.89), and no association among women in the highest quartile (OR: 0.93, 95% CI: 0.77-1.13). No differences in these patterns were observed by ovarian cancer histotype (p-heterogeneity=0.51). Conclusions: This study suggests that genetic susceptibility to ovarian cancer may modify the association between frequent aspirin use and ovarian cancer risk, with a protective association seen only among women at increased genetic risk. Any use of aspirin for ovarian cancer chemoprevention may be unlikely to benefit women at below-average genetic risk of ovarian cancer.
Keywords: aspirin, epithelial ovarian cancer, polygenic risk score