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Morning chronotype and digestive tract cancers: Mendelian randomization study.

Authors
  • Yuan, Shuai1
  • Mason, Amy M2
  • Titova, Olga E3
  • Vithayathil, Mathew4
  • Kar, Siddhartha5
  • Chen, Jie6
  • Li, Xue7
  • Burgess, Stephen8, 9
  • Larsson, Susanna C1, 3
  • 1 Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. , (Sweden)
  • 2 Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. , (Sweden)
  • 3 British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • 4 MRC Cancer Unit, University of Cambridge, Cambridge, UK.
  • 5 MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK.
  • 6 Centre for Global Health, Zhejiang University School of Medicine, Hangzhou, China. , (China)
  • 7 Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. , (China)
  • 8 MRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
  • 9 Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Type
Published Article
Journal
International Journal of Cancer
Publisher
Wiley (John Wiley & Sons)
Publication Date
Feb 15, 2023
Volume
152
Issue
4
Pages
697–704
Identifiers
DOI: 10.1002/ijc.34284
PMID: 36093575
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Morning chronotype has been associated with a reduced risk of prostate and breast cancer. However, few studies have examined whether chronotype is associated with digestive tract cancer risk. We conducted a Mendelian randomization (MR) study to assess the associations of chronotype with major digestive tract cancers. A total of 317 independent genetic variants associated with chronotype at the genome-wide significance level (P < 5 × 10-8 ) were used as instrumental variables from a genome-wide meta-analysis of 449 734 individuals. Summary-level data on overall and six digestive tract cancers, including esophageal, stomach, liver, biliary tract, pancreatic and colorectal cancers, were obtained from the UK Biobank (11 952 cases) and FinnGen (7638 cases) study. Genetic liability to morning chronotype was associated with reduced risk of overall digestive tract cancer and cancers of stomach, biliary tract and colorectum in UK Biobank. The associations for the overall digestive tract, stomach and colorectal cancers were directionally replicated in FinnGen. In the meta-analysis of the two sources, genetic liability to morning chronotype was associated with a decreased risk of overall digestive tract cancer (odds ratio [OR] 0.94, 95% confidence interval [CI]: 0.90-0.98), stomach cancer (OR 0.84, 95% CI: 0.73-0.97) and colorectal cancer (OR 0.92, 95% CI: 0.87-0.98), but not with the other studied cancers. The associations were consistent in multivariable MR analysis with adjustment for genetically predicted sleep duration, short sleep, insomnia and body mass index. The study provided MR evidence of inverse associations of morning chronotype with digestive tract cancer, particularly stomach and colorectal cancers. © 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

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