Ulcerative colitis and estrogen receptor-negative breast cancer risk: a Mendelian randomized study

BACKGROUND Some studies have suggested a potential association between ulcerative colitis (UC) and estrogen receptor-negative breast cancer. However, whether there is a causal relationship between the two is currently unknown. In this study, we will investigate the relationship between UC and estrogen receptor-negative breast cancer risk from a genetic perspective. OBJECTIVE This study explored the causal relationship between UC and estrogen receptor-negative breast cancer risk. METHODS Patients with UC (n=27,432) and estrogen receptor-negative breast cancer (n=22,068) who met the same ethnicity and came from different regions were selected. The causal relationship between UC and estrogen receptor-negative breast cancer risk was evaluated by five methods, namely, Mendelian randomised Egger regression, median weighted, IVW random effects model, IVW radial method, and IVW fixed effects model, respectively, with OR. Sensitivity analyses were performed using Cochran's Q test, MR⁃Egger regression intercept term, MR⁃PRESSO, and leave-one-out method to assess the stability and reliability of the results. RESULTS European ethnicity was the basis of GWAS data on screened UC and estrogen receptor-negative breast cancers. In MR analysis, we found that genetically predicted UC was associated with an increased risk of estrogen receptor-negative breast cancer, and the results of Weighted median, Simple mode, Weighted mode, and MR Egger all showed similar trends (OR=1.07, 95% CI:1.03-1.11). The results of sensitivity analyses remained consistent, suggesting that UC is associated with a high prevalence of estrogen receptor-negative breast cancer. CONCLUSION Our findings suggest that patients with UC have an increased risk of developing estrogen receptor-negative breast cancer.