Associations Between Glycemic Traits and Colorectal Cancer: A Mendelian Randomization Analysis.
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Authors
Papadimitriou, Nikos
Chen, Ji
Cotterchio, Michelle
Newcomb, Polly A
Vodicka, Pavel
Wu, Anna H
Peters, Ulrike
Publication Date
2022-05-09Journal Title
J Natl Cancer Inst
ISSN
0027-8874
Publisher
Oxford University Press (OUP)
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Murphy, N., Song, M., Papadimitriou, N., Carreras-Torres, R., Langenberg, C., Martin, R. M., Tsilidis, K. K., et al. (2022). Associations Between Glycemic Traits and Colorectal Cancer: A Mendelian Randomization Analysis.. J Natl Cancer Inst https://doi.org/10.1093/jnci/djac011
Abstract
BACKGROUND: 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 2-sample MR, we examined these variants in relation to colorectal cancer risk (48 214 case patient and 64 159 control patients). RESULTS: In inverse-variance models, higher fasting insulin levels increased colorectal cancer risk (odds ratio [OR] per 1-SD = 1.65, 95% confidence interval [CI] = 1.15 to 2.36). We found no evidence of any effect of 2-hour glucose (OR per 1-SD = 1.02, 95% CI = 0.86 to 1.21) or fasting glucose (OR per 1-SD = 1.04, 95% CI = 0.88 to 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 to 1.07) and higher HbA1c levels (OR per 1-SD = 1.09, 95% CI = 1.00 to 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 to 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.
Keywords
Mendelian randomization, glucose, glycemic traits, insulin, type-2 diabetes colorectal cancer
Sponsorship
MRC (MC_UU_00006/1)
Medical Research Council (G1000143)
Embargo Lift Date
2023-01-20
Identifiers
External DOI: https://doi.org/10.1093/jnci/djac011
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333410
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