Genetically proxied morning chronotype was associated with a reduced risk of prostate cancer

Observational epidemiological studies have suggested that chronotype may play a role in the pathogenesis and progression of prostate cancer. However, whether there is a causal association remains unknown. The aim of the present study was to examine the potential causal relationship between chronotype and prostate cancer risk using a Mendelian randomization (MR) design.

A total of 268 single nucleotide polymorphisms associated with chronotype were selected from a meta-analysis of genome-wide association studies of 697,828 individuals. The genetic association data for prostate cancer was derived from the Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome (PRACTICAL) Consortium (79,148 cases and 61,106 controls). Inverse-variance weighted (IVW) method was used as the primary analysis to calculate the causal effect estimates. The weighted-median method, MR-Egger regression, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) test, and multivariable MR analyses were applied as sensitivity analysis.

Genetically predicted morningness (scaled to a sleep midpoint of 1 h earlier) had a reduced risk of prostate cancer, with an odds ratio of 0.71 (95% confidence interval [CI]: 0.54-0.94 by IVW), compared with the eveningness. Similar causal effect estimates were also observed by using the weighted median and MR-PRESSO analyses. In addition, results from the multivariable MR analysis supported the findings from the univariable MR analyses. No indication of horizontal pleiotropy was observed in the MR-Egger analysis (p for intercept = 0.234).

Our findings provide evidence of a causal protective effect of morning chronotype on the risk of prostate cancer.