Breast cancer risk in patients with polycystic ovary syndrome: a Mendelian randomization analysis
BREAST CANCER RESEARCH AND TREATMENT(2020)
摘要
Purpose 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-variance 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 methods 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). In addition, no pleiotropy was found in our study. 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.
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关键词
Breast cancer,Polycystic ovary syndrome,Mendelian randomization,Causality
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