Morning chronotype and digestive tract cancers: Mendelian randomization study

Shuai Yuan, Amy M. Mason, Olga E. Titova, Mathew Vithayathil, Siddhartha Kar, Jie Chen, Xue li, Stephen Burgess, Susanna C. Larsson*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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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.
Original languageEnglish
Pages (from-to)697-704
Number of pages8
JournalInternational Journal of Cancer
Volume152
Issue number4
DOIs
Publication statusPublished - 12 Sept 2022

Bibliographical note

Funding Information:
Our study was supported by funding from the Swedish Cancer Society (Cancerfonden) and by core funding from the: United Kingdom Research and Innovation Medical Research Council (MC_UU_00002/7), British Heart Foundation (RG/13/13/30194; RG/18/13/33946) and NIHR Cambridge Biomedical Research Centre (BRC‐1215‐20014) [*]. SCL further acknowledges research support from the Swedish Heart‐Lung Foundation (Hjärt‐Lungfonden) (20210351), the Swedish Research Council for Health, Working Life and Welfare (Forte); grant no. 2018‐00123 and the Swedish Research Council (Vetenskapsrådet); grant no. 2019‐00977. XL is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001). AMM is funded by the EU/EFPIA Innovative Medicines Initiative Joint Undertaking BigData@Heart grant 116074. SB is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (204623/Z/16/Z). *The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Funding Information:
British Heart Foundation, Grant/Award Numbers: RG/13/13/30194, RG/18/13/33946; Swedish Cancer Society (Cancerfonden); NIHR Cambridge Biomedical Research Centre, Grant/Award Number: BRC‐1215‐20014; United Kingdom Research and Innovation Medical Research Council, Grant/Award Number: MC_UU_00002/7; Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society, Grant/Award Number: 204623/Z/16/Z; EU/EFPIA Innovative Medicines Initiative Joint Undertaking BigData@Heart, Grant/Award Number: 116074; Natural Science Fund for Distinguished Young Scholars of Zhejiang Province, Grant/Award Number: LR22H260001; Swedish Research Council (Vetenskapsrådet), Grant/Award Number: 2019‐00977; Swedish Research Council for Health, Working Life and Welfare (Forte), Grant/Award Number: 2018‐00123; Swedish Heart‐Lung Foundation (Hjärt‐Lungfonden), Grant/Award Number: 20210351 Funding information

Publisher Copyright:
© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

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