Association between circadian rhythm-related behaviors and breast cancer: a bidirectional Mendelian randomization study

Background Breast cancer (BC) is a major cause of cancer-related morbidity and mortality in women, with its development linked to circadian rhythm disruption. This study employs two-sample bidirectional Mendelian randomization (MR) to explore their causal relationship.Materials and Methods Genome-wide association study (GWAS) from the MRC Integrated Epidemiology Unit (MRC IEU) on circadian rhythm-related behaviors and BC subtypes was used. Causal effects were assessed using multiple MR methods, with IVW as the primary approach. Sensitivity analyses were conducted to ensure result robustness.Results Increased sleep duration was associated with a higher BC risk (IVW model: OR = 1.33, P < 0.001), while being a morning person (IVW model: OR = 0.76, P = 0.003) and getting up in the morning (IVW model: OR = 0.71, P < 0.001) were protective factors. Similar findings were observed for estrogen receptor-positive (ER+) BC. BC patients were also more likely to experience insomnia (IVW model: OR = 1.01, P < 0.001).Conclusion Our bidirectional MR study provides genetic evidence for a causal link between genetically predicted circadian rhythm-related behaviors and BC. These findings underscore the role of genetic factors influencing circadian biology in BC etiology and warrant further investigation into the underlying mechanisms.