237P Breast cancer risk in patients with polycystic ovary syndrome: A Mendelian randomization analysis

Abstract

The association between polycystic ovary syndrome (PCOS) and breast cancer remains inconclusive. Conventional observational studies are susceptible to inverse causality and potential confounders. With a Mendelian randomization (MR) approach, we aimed to investigate the causal relationship between genetically predicted PCOS and breast cancer risk. Our study included 11 PCOS-associated single nucleotide polymorphisms as instrumental variables identified by the latest genome-wide association study. Individual-level genetic summary data of participants were obtained from the Breast Cancer Association Consortium, with a total of 122 977 cases and 105 974 controls. The Inverse-weighted method was applied to estimate the causality between genetically predicted PCOS and breast cancer risk. To further evaluate the pleiotropy, the weighted median and MR-Egger regression method were implemented as well. Our study demonstrated that genetically predicted PCOS was causally associated with an increased risk of overall breast cancer (odds ratio (OR) = 1.07; 95% confidence interval (CI) = 1.02-1.12, p = 0.005). The subgroup analyses according to immunohistochemical type further illustrated that genetically predicted PCOS was associated with an increased risk of estrogen receptor (ER)-positive breast cancer (OR = 1.09; 95% CI = 1.03-1.15, p = 0.002), while no causality was observed for ER-negative breast cancer (OR = 1.02; 95% CI = 0.96-1.09, p = 0.463). Additionally, no horizontal pleiotropy was found in our study.Table 237PMendelian randomization estimates of the causality between PCOS and breast cancer.OutcomeIVW methodMR-EggerWeighted median methodOR (95% CI)P-valueOR (95% CI)P-valueOR (95% CI)P-valueBreast cancer overall1.0667 (1.0200, 1.1155)0.00471.0450 (0.8351, 1.3077)0.70931.0742 (1.0226, 1.1283)0.0043ER-positive breast cancer1.0881 (1.0318, 1.1474)0.00181.0901 (0.8352, 1.4227)0.54141.0992 (1.0346, 1.1678)0.0022ER-negative breast cancer1.0242 (0.9609, 1.0917)0.46280.8817 (0.6507, 1.1947)0.43761.0063 (0.9275, 1.0919)0.8793 Open table in a new tab Our findings indicated that PCOS was likely to be a causal factor in the development of ER-positive breast cancer, providing a better understanding for the etiology of breast cancer and the prevention of breast cancer.