Abstract 237P
Background
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.
Methods
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.
Results
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: 237P
Mendelian randomization estimates of the causality between PCOS and breast cancer.
| Outcome | IVW method | MR-Egger | Weighted median method | |||
| OR (95% CI) | P-value | OR (95% CI) | P-value | OR (95% CI) | P-value | |
| Breast cancer overall | 1.0667 (1.0200, 1.1155) | 0.0047 | 1.0450 (0.8351, 1.3077) | 0.7093 | 1.0742 (1.0226, 1.1283) | 0.0043 |
| ER-positive breast cancer | 1.0881 (1.0318, 1.1474) | 0.0018 | 1.0901 (0.8352, 1.4227) | 0.5414 | 1.0992 (1.0346, 1.1678) | 0.0022 |
| ER-negative breast cancer | 1.0242 (0.9609, 1.0917) | 0.4628 | 0.8817 (0.6507, 1.1947) | 0.4376 | 1.0063 (0.9275, 1.0919) | 0.8793 |
Conclusions
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Jianxing He.
Funding
National Key R&D Program of China; China National Science Foundation; Key Project of Guangzhou Scientific Research Project; High-level university construction project of Guangzhou Medical University; IVATS National key R&D Program; Application, industrialization and generalization of surgical incision protector.
Disclosure
All authors have declared no conflicts of interest.