Abstract
BACKGROUND: Sleep traits may influence cancer risk; however, their associations with prostate (PCa), endometrial (ECa), and epithelial ovarian (EOCa) cancer remain unclear. METHODS: We conducted an observational analysis using the UK Biobank cohort and a two-sample Mendelian randomisation (MR) analysis to investigate the association of six sleep traits-duration, chronotype, insomnia, daytime napping, daytime sleepiness, and snoring-with PCa, ECa, and EOCa risk. Cox proportional hazards models were used for the observational analysis, while the inverse variance-weighted (IVW) method was applied in MR, with multiple sensitivity analyses. A Bonferroni correction accounted for multiple testing. RESULTS: Among 8,608 PCa, 1,079 ECa, and 680 EOCa incident diagnoses (median follow-up: 6.9 years), snoring was associated with reduced EOCa risk (HR=0.78, 95%CI: 0.62-0.98), while daytime sleepiness was associated with increased EOCa risk (HR=1.23, 95%CI: 1.03-1.47). However, these associations were not confirmed in MR. MR suggested higher odds of PCa (OR (IVW) =1.05, 95%CI: 1.01-1.11) and aggressive PCa (OR (IVW) =1.10, 95%CI: 1.02-1.19) for evening compared to morning chronotype. None of the findings survived multiple testing correction. CONCLUSION: Sleep traits were not associated with PCa, ECa, or EOCa risk, but evening chronotype may increase PCa risk. Further research is needed to verify this association and investigate potential underlying mechanisms. IMPACT: The proposed results have potential utility in reproductive cancer prevention. WHAT IS ALREADY KNOWN ON THIS TOPIC: Sleep traits have been implicated in cancer risk, but their associations with prostate, endometrial, and epithelial ovarian cancer remain unclear. WHAT THIS STUDY ADDS: This study found suggestive evidence that an evening chronotype may be associated with an increased risk of overall and aggressive prostate cancer. HOW THIS STUDY MIGHT AFFECT RESEARCH PRACTICE OR POLICY: Further research is needed to confirm the potential association between chronotype and prostate cancer risk, which could inform personalised cancer prevention strategies.