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

Abstract

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.