Abstract
This study used a Mendelian randomization (MR) approach to investigate the causal relationship between genetically predicted endometriosis (EMS) and breast cancer risk. A total of 122,977 cases and 105,974 controls were included in the analysis, with gene-level summary data obtained from the Breast Cancer Association Consortium (BCAC). An inverse variance-weighting approach was applied to assess the causal relationship between EMS and breast cancer risk, and weighted median and MR-Egger regression methods were used to evaluate pleiotropy. Results showed a causal relationship between EMS and a decreased risk of overall breast cancer (odds ratio [OR] 0.95; 95% CI 0.90–0.99, p = 0.02). Furthermore, EMS was associated with a lower risk for estrogen receptor (ER)-positive breast cancer in a subgroup analysis based on immunohistochemistry type (OR 0.91; 95% CI 0.86–0.97, p = 0.005). However, there was no causal association between ER-negative breast cancer and survival (OR 1.00; 95% CI 0.94–1.06, p = 0.89). Pleiotropy was not observed. These findings provide evidence of a relationship between EMS and reduced breast cancer risk in invasive breast cancer overall and specific tissue types, and support the results of a previous observational study. Further research is needed to elucidate the mechanisms underlying this association.
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