The Relationship between Modifiable Lifestyle Factors and Breast Diseases: A Mendelian Randomization Study

Abstract

Background This study aimed to employ mendelian randomization to systematically investigate the causal effects of genetic predispositions and modifiable lifestyle factors on breast diseases. MethodsIn this mendelian randomization study, we leveraged large-scale genetic data from genome-wide association studies (GWAS) to assess the causal effects of modifiable lifestyle factors. Instrumental variable analysis was performed using genetic variants associated with each lifestyle factor as instruments. Sensitivity analyses were conducted to assess the robustness of findings. Results We applied instrumental variable weighted (IVW) analysis to investigate causal link. Specifically, an increased risk of overall BC was observed with longer sleep duration (OR=1.33, 95% CI: 1.01-1.74, P=0.04) and decreased with more years of schooling (OR=0.91, 95% CI: 0.83-0.99, P=0.04) and greater fresh fruit intake (OR=0.64, 95% CI: 0.46-0.90, P=0.01). For ER+ BC, both increased sleep duration (OR=1.49, 95% CI: 1.12-2.00, P=0.007) and greater fresh fruit consumption (OR=0.65, 95% CI: 0.44-0.95, P=0.02) showed significant associations. In contrast, the risk of developing ER-BC decreased with increased education (OR=0.73, 95% CI: 0.64-0.84, P=0.000005) and fresh fruit intake (OR=0.55, 95% CI: 0.31-0.99, P=0.04) but increased with increased processed meat consumption (OR=1.78, 95% CI: 1.11-2.84, P=0.016). Benign neoplasm of breast was linked to higher physical activity levels (OR=3.13, 95% CI: 1.07-9.10, P=0.0368), more years of education (OR=0.63, 95% CI: 0.46-0.866, P=0.003), and greater processed meat consumption (OR=3.84, 95% CI: 1.25-11.84, P=0.019). Moreover, inflammatory disorders of breast were correlated with pack years of smoking (OR=4.18, 95% CI: 1.10-15.70, P=0.034), higher BMI (OR=1.97, 95% CI: 1.40-2.72, P=0.00004), and fewer years of schooling (OR=0.47, 95% CI: 0.29-0.77, P=0.003). These findings underscore the complexity of lifestyle influences on different types of breast pathologies and highlight the importance of considering specific disease mechanisms in lifestyle recommendations. Conclusions This MR study provides evidence supporting the significant role of modifiable lifestyle factors in breast diseases. The findings underscore the importance of adopting healthy lifestyle habits for the prevention and management of breast diseases.