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

• Published in: Sleep (New York, N.Y.) Vol. 44; no. 10; p. 1
• Main Authors: Sun, Xiaohui, Ye, Ding, Jiang, Mengting, Qian, Yu, Mao, Yingying
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.10.2021
• Subjects: Cancer; Chromosomes; Development and progression; Epidemiology; Genetic aspects; Genomes; Genomics; Health aspects; Oncology, Experimental; Prevention; Prostate cancer; Risk factors; Single nucleotide polymorphisms; Systematic review; China; chronotype; prostate cancer; Mendelian randomization; morningness–eveningness; morningness-eveningness
• ISSN: 0161-8105; 1550-9109; 1550-9109
• DOI: 10.1093/sleep/zsab104

Abstract Study Objectives 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. Methods 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. Results 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). Conclusion Our findings provide evidence of a causal protective effect of morning chronotype on the risk of prostate cancer.