Morning Chronotype and Digestive Tract Cancers : Mendelian Randomization Study

• 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 oesophageal, 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. This article is protected by copyright. All rights reserved.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)

Keyword

Mendelian randomization

chronotype

colorectal cancer

digestive system cancer

gastric cancer

Publication and Content Type

ref (subject category)

art (subject category)