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Morning chronotype and digestive tract cancers: Mendelian randomization study.

Published version
Peer-reviewed

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Authors

Mason, Amy M 
Titova, Olga E 
Vithayathil, Mathew 
Kar, Siddhartha 

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.

Description

Funder: Swedish Cancer Society (Cancerfonden); Id: http://dx.doi.org/10.13039/501100002794

Keywords

Mendelian randomization, chronotype, colorectal cancer, digestive system cancer, gastric cancer, Male, Humans, Chronotype, Mendelian Randomization Analysis, Gastrointestinal Neoplasms, Colorectal Neoplasms, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Risk Factors

Journal Title

Int J Cancer

Conference Name

Journal ISSN

0020-7136
1097-0215

Volume Title

Publisher

Wiley
Sponsorship
Wellcome Trust (204623/Z/16/Z)
British Heart Foundation (None)
British Heart Foundation (RG/18/13/33946)
Medical Research Council (MC_UU_00002/7)
National Institute for Health and Care Research (IS-BRC-1215-20014)