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dc.contributor.authorMurphy, N.
dc.contributor.authorSong, M.
dc.contributor.authorPapadimitriou, N.
dc.contributor.authorCarreras-Torres, R.
dc.contributor.authorLangenberg, C.
dc.contributor.authorMartin, R. M.
dc.contributor.authorTsilidis, K. K.
dc.contributor.authorBarroso, I.
dc.contributor.authorChen, J.
dc.contributor.authorFrayling, T.
dc.contributor.authorBull, C. J.
dc.contributor.authorVincent, E. E.
dc.contributor.authorCotterchio, M.
dc.contributor.authorGruber, S. B.
dc.contributor.authorPai, R. K.
dc.contributor.authorNewcomb, P. A.
dc.contributor.authorPerez-Cornago, A.
dc.contributor.authorvan Duijnhoven, F. J. B.
dc.contributor.authorVan Guelpen, B.
dc.contributor.authorVodicka, P.
dc.contributor.authorWolk, A.
dc.contributor.authorWu, A. H.
dc.contributor.authorPeters, U.
dc.contributor.authorChan, A. T.
dc.contributor.authorGunter, M. J.
dc.identifier.citationJ Natl Cancer Inst. 2022 Jan 20:djac011. doi: 10.1093/jnci/djac011.
dc.description.abstractBACKGROUND: Glycemic traits-such as hyperinsulinemia, hyperglycemia, and type-2 diabetes-have been associated with higher colorectal cancer risk in observational studies; however, causality of these associations is uncertain. We used Mendelian randomization (MR) to estimate the causal effects of fasting insulin, 2-hour glucose, fasting glucose, glycated hemoglobin (HbA1c), and type-2 diabetes with colorectal cancer. METHODS: Genome-wide association study summary data were used to identify genetic variants associated with circulating levels of fasting insulin (n = 34), 2-hour glucose (n = 13), fasting glucose (n = 70), HbA1c (n = 221), and type-2 diabetes (n = 268). Using two-sample MR, we examined these variants in relation to colorectal cancer risk (48,214 cases and 64,159 controls). RESULTS: In inverse-variance models, higher fasting insulin levels increased colorectal cancer risk (odds ratio [OR] per 1-standard deviation [SD]=1.65, 95% CI = 1.15-2.36). We found no evidence of any effect of 2-hour glucose (OR per 1-SD = 1.02, 95% CI = 0.86-1.21) or fasting glucose (OR per 1-SD = 1.04, 95% CI = 0.88-1.23) concentrations on colorectal cancer risk. Genetic liability to type-2 diabetes (OR per 1-unit increase in log odds = 1.04, 95% CI = 1.01-1.07) and higher HbA1c levels (OR per 1-SD = 1.09, 95% CI = 1.00-1.19) increased colorectal cancer risk, although these findings may have been biased by pleiotropy. Higher HbA1c concentrations increased rectal cancer risk in men (OR per 1-SD = 1.21, 95% CI = 1.05-1.40), but not in women. CONCLUSIONS: Our results support a causal effect of higher fasting insulin, but not glucose traits or type-2 diabetes, on increased colorectal cancer risk. This suggests that pharmacological or lifestyle interventions that lower circulating insulin levels may be beneficial in preventing colorectal tumorigenesis.
dc.publisherOxford University Press
dc.rights© The Author(s) 2022. Published by Oxford University Press.
dc.subjectMendelian randomization
dc.subjectglycemic traits
dc.subjecttype-2 diabetes colorectal cancer
dc.titleAssociations Between Glycemic Traits and Colorectal Cancer: A Mendelian Randomization Analysis
dc.typeJournal Article
dc.identifier.journalJournal of the National Cancer Institute
dc.description.noteThe article is available via Open Access. Click on the 'Additional link' above to access the full-text.
dc.description.admin-noteAccepted version (12 month embargo), submitted version

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