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Sleep duration and risk of overall and 22 site-specific cancers: A Mendelian randomization study.

Accepted version
Peer-reviewed

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Article

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Authors

Michaëlsson, Karl 
Vithayathil, Mathew 
Mason, Amy M 
Kar, Siddhartha 

Abstract

Studies of sleep duration in relation to the risk of site-specific cancers other than breast cancer are scarce. Furthermore, the available results are inconclusive and the causality remains unclear. We aimed to investigate the potential causal associations of sleep duration with overall and site-specific cancers using the Mendelian randomization (MR) design. Single-nucleotide polymorphisms associated with the sleep traits identified from a genome-wide association study were used as instrumental variables to estimate the association with overall cancer and 22 site-specific cancers among 367 586 UK Biobank participants. A replication analysis was performed using data from the FinnGen consortium (up to 121 579 individuals). There was suggestive evidence that genetic liability to short-sleep duration was associated with higher odds of cancers of the stomach (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.15-4.30; P = .018), pancreas (OR, 2.18; 95% CI, 1.32-3.62; P = .002) and colorectum (OR, 1.48; 95% CI, 1.12-1.95; P = .006), but with lower odds of multiple myeloma (OR, 0.47; 95% CI, 0.22-0.99; P = .047). Suggestive evidence of association of genetic liability to long-sleep duration with lower odds of pancreatic cancer (OR, 0.44; 95% CI, 0.25-0.79; P = .005) and kidney cancer (OR, 0.44; 95% CI, 0.21-0.90; P = .025) was observed. However, none of these associations passed the multiple comparison threshold and two-sample MR analysis using FinnGen data did not confirm these findings. In conclusion, this MR study does not provide strong evidence to support causal associations of sleep duration with risk of overall and site-specific cancers. Further MR studies are required.

Description

Keywords

Mendelian randomization, cancer, single-nucleotide polymorphisms, sleep, Adult, Aged, Biological Specimen Banks, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Neoplasms, Odds Ratio, Polymorphism, Single Nucleotide, Risk Factors, Sleep, Time Factors, United Kingdom

Journal Title

Int J Cancer

Conference Name

Journal ISSN

0020-7136
1097-0215

Volume Title

148

Publisher

Wiley

Rights

All rights reserved
Sponsorship
Wellcome Trust (204623/Z/16/Z)
European Commission and European Federation of Pharmaceutical Industries and Associations (EFPIA) FP7 Innovative Medicines Initiative (IMI) (116074)
Medical Research Council (MC_UU_00002/7)