Mendelian randomization study of sleep traits and risk of colorectal cancer.

Authors

Dimopoulou O, Fuller H, Richmond RC, Bouras E, Hayes B, Dimou N, Murphy N, Brenner H, Gsur A, Le Marchand L, Moreno V, Pai RK, Phipps AI, Um CY, van Duijnhoven FJB, Vodicka P, Martin RM, Platz EA, Gunter MJ, Peters U, ...show more Lewis SJ, Cao Y, Tsilidis KK

Affiliations

• Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. olympia.dimopoulou@bristol.ac.uk.
• Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
• Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
• Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
• Nutrition and Metabolism Branch, International Agency for Research On Cancer-WHO, Lyon, France.
• Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
• Center for Cancer Research, Medical University of Vienna, Vienna, Austria.
• University of Hawaii Cancer Center, Honolulu, HI, USA.
• Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
• Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA.

Abstract

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 (OR_IVW = 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.