A potential association of endogenous circadian rhythm disruption with risk of cancer development has been suggested, however, epidemiological evidence for the association of sleep traits with colorectal cancer (CRC) is limited and often contradictory. Here we investigated whether genetically predicted chronotype, insomnia and sleep duration are associated with CRC risk in males, females and overall and according to CRC anatomical subsites using Mendelian randomization (MR). The two-sample inverse variance weighted (IVW) method was applied using summary-level data in up to 58,221 CRC cases and 67,694 controls and genome-wide association data of genetic variants for self-reported sleep traits. Secondary analyses using alternative instruments and sensitivity analyses assessing potential violations of MR assumptions were conducted. Genetically predicted morning preference was associated with 13% lower risk of CRC in men (ORIVW = 0.87, 95% CI = 0.78, 0.97, P = 0.01), but not in women or in both sexes combined. Τhis association remained consistent in some, but not all, sensitivity analyses and was very similar for colon and rectal cancer. There was no evidence of an association for any other sleep trait. Overall, this study provides little to no evidence of an association between genetically predicted sleep traits and CRC risk.

Alvin J Siteman Cancer Center Washington University School of Medicine St Louis MO USA

Center for Cancer Research Medical University of Vienna Vienna Austria

CIBER Epidemiología y Salud Pública Madrid Spain

Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona Spain

Department of Epidemiology and Biostatistics School of Public Health Imperial College London London UK

Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USA

Department of Epidemiology University of Washington Seattle WA USA

Department of Hygiene and Epidemiology University of Ioannina School of Medicine Ioannina Greece

Department of Laboratory Medicine and Pathology Mayo Clinic Arizona Scottsdale AZ USA

Department of Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences Prague Czech Republic

Department of Population Health Sciences Bristol Medical School University of Bristol Bristol UK

Division of Clinical Epidemiology and Aging Research German Cancer Research Center Heidelberg Germany

Division of Gastroenterology Department of Medicine Washington University School of Medicine St Louis MO USA

Division of Human Nutrition Wageningen University and Research Wageningen The Netherlands

Division of Preventive Oncology German Cancer Research Center Heidelberg Germany

Division of Public Health Sciences Department of Surgery Washington University in St Louis St Louis MO USA

Faculty of Medicine and Biomedical Center in Pilsen Charles University Pilsen Czech Republic

German Cancer Consortium Heidelberg Germany

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Prague Czech Republic

MRC Integrative Epidemiology Unit Population Health Sciences Bristol Medical School University of Bristol Bristol UK

Nutrition and Metabolism Branch International Agency for Research On Cancer WHO Lyon France

ONCOBEL Program Bellvitge Biomedical Research Institute L'Hospitalet de Llobregat Barcelona Spain

Oncology Data Analytics Program Catalan Institute of Oncology IDIBELL L'Hospitalet de Llobregat Barcelona Spain

Population Science Department American Cancer Society Atlanta GA USA

Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore MD USA

University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol National Institute for Health Research Bristol Biomedical Research Centre University of Bristol Bristol UK

University of Hawaii Cancer Center Honolulu HI USA

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