Genetically predicted sleep duration in relation to the risk of breast tumors

Abstract

Aim To investigate the causal relationship between genetically predicted sleep duration and breast tumors using a bidirectional two-sample Mendelian randomization (MR) analysis. Methods A bidirectional two-sample MR analysis was performed using genome-wide association study (GWAS) summary statistics. The inverse variance-weighted (IVW) method was used as the primary analysis, with MR-Egger regression, weighted median, weighted mode, and simple mode analyses conducted for validation. Sensitivity analyses, including heterogeneity, horizontal pleiotropy, and leave-one-out tests, were performed to evaluate the robustness of the findings. Reverse MR analysis was conducted to assess whether breast tumors causally influence sleep duration. Results Genetically predicted longer sleep duration was associated with an increased risk of breast cancer (OR = 1.328, 95% CI: 1.013–1.741, P = .04). Borderline associations were observed for ER+ (P = .051) and ER− (P = .077) breast cancer, whereas no significant causal association was found for HER2+/HER2− breast cancer, benign breast tumors, or carcinoma in situ. Sensitivity analyses supported the robustness of the main findings despite heterogeneity. Reverse MR analysis showed no evidence that breast cancer or its molecular subtypes causally affected sleep duration. Conclusion This study provides evidence that genetically predicted longer sleep duration may increase the risk of breast cancer but not benign breast tumors or carcinoma in situ. No reverse causal relationship between breast tumors and sleep duration was identified. These findings suggest that genetically predicted longer sleep duration may be associated with breast cancer risk; however, further studies are needed to confirm the clinical implications.