Mendelian randomization study of sleep traits and risk of colorectal cancer

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<sub>IVW</sub> = 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.

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Publication Details

Journal
Scientific Reports
Published
2025-04-18
DOI
https://doi.org/10.1038/s41598-024-83693-w
Citations
2
Primary Topic
Circadian rhythm and melatonin
Type
article
Field-Weighted Citation Impact
1.83

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article

Mendelian randomization study of sleep traits and risk of colorectal cancer

Pavel Vodička, Konstantinos K. Tsilidis, Harriett Fuller, Andrea Gsur et al.
2 citations
Scientific Reports
Circadian rhythm and melatonin
1.83
article

Mendelian randomization study of sleep traits and risk of colorectal cancer

Pavel Vodička, Konstantinos K. Tsilidis, Harriett Fuller, Andrea Gsur, Amanda I. Phipps, Olympia Dimopoulou, Elizabeth A. Platz, Bryony Hayes, Yin Cao, Niki L. Dimou, Vı́ctor Moreno, Loı̈c Le Marchand, Ulrike Peters, Sarah Jayne Lewis, Rish K. Pai, Fränzel J.B. van Duijnhoven, Neil Murphy, Richard Michael Martin, Rebecca C. Richmond, Marc J. Gunter, Hermann Brenner, Emmanouil Bouras, Caroline Y. Um
article en
2 citations

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<sub>IVW</sub> = 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.

Scientific ReportsVol. 15(1)
University of Hawaiʻi at Mānoa (US), American Cancer Society (US), University of Hawaii System (US), Johns Hopkins University (US), German Cancer Research Center (DE), University of Ioannina (GR), University of Washington (US), Washington University in St. Louis (US), Charles University (CZ), Heidelberg University (DE), University Hospitals Bristol NHS Foundation Trust (GB), University of Bristol (GB), Institut d'Investigació Biomédica de Bellvitge (ES), Fred Hutch Cancer Center (US), Comprehensive Cancer Center Vienna (AT), Cancer Center of Hawaii (US), Institut Català d'Oncologia (ES), National Center for Tumor Diseases (DE), Mayo Clinic in Arizona (US), Czech Academy of Sciences, Institute of Experimental Medicine (CZ), Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES), Sidney Kimmel Comprehensive Cancer Center (US), Centre international de recherche sur le cancer (FR), University of Hawaii Cancer Center, Alvin J. Siteman Cancer Center (US), Imperial College London (GB), Universitat de Barcelona (ES), Medical University of Vienna (AT), Wageningen University & Research (NL)
U.S. Department of Health and Human Services, Damon Runyon Cancer Research Foundation, World Health Organization, Brigham and Women's Hospital, Fred Hutchinson Cancer Research Center, Florida Department of Health, Memorial Sloan-Kettering Cancer Center, Division of Cancer Prevention, National Cancer Institute, Association Anne de Bretagne Genetique, Johns Hopkins University, University of Pittsburgh, Harvard T.H. Chan School of Public Health, McGill University, University of South Florida, Moffitt Cancer Center, Mike and Josie Harper Cancer Research Institute, University Hospitals Bristol NHS Foundation Trust, Génome Québec, NIHR Bristol Biomedical Research Centre, Centres de Recerca de Catalunya, Pelotonia, Cancer Research UK, National Institute for Health and Care Research, Department of Health and Social Care, Food Standards Agency, University of Cambridge, University of Bristol, Chonnam National University, Fundación Científica Asociación Española Contra el Cáncer, Cancerfonden, Generalitat de Catalunya, Ministerio de Economía y Competitividad, Knut och Alice Wallenbergs Stiftelse, Vetenskapsrådet, Umeå Universitet, Deutsche Krebshilfe, Karl-Franzens-Universität Graz, Centre Hospitalier Universitaire de Nantes, Medizinische Universität Graz, Xunta de Galicia, Conseil Régional des Pays de la Loire, Biobanco Vasco, Groupement des Entreprises Françaises dans la lutte contre le Cancer, Chonnam National University Hwasun Hospital, National Institutes of Health, Centers for Disease Control and Prevention, Canadian Institutes of Health Research, Canadian Cancer Society Research Institute, Medical Research Council, National Health and Medical Research Council, Cancer Council Victoria, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, Wageningen University and Research, National Cancer Institute, National Center for Advancing Translational Sciences, Office of Research Infrastructure Programs, National Institutes of Health
Good health and well-being
Openalex Percentile: Top 16%
Circadian rhythm and melatonin
1.83
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