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Associations Between Glycemic Traits and Colorectal Cancer: A Mendelian Randomization Analysis

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F22%3A00568742" target="_blank" >RIV/68378041:_____/22:00568742 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11110/22:10439489 RIV/00216208:11140/22:10439489

  • Result on the web

    <a href="https://academic.oup.com/jnci/article/114/5/740/6512063?login=true" target="_blank" >https://academic.oup.com/jnci/article/114/5/740/6512063?login=true</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1093/jnci/djac011" target="_blank" >10.1093/jnci/djac011</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Associations Between Glycemic Traits and Colorectal Cancer: A Mendelian Randomization Analysis

  • Original language description

    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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10603 - Genetics and heredity (medical genetics to be 3)

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2022

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    JNCI-Journal of the National Cancer Institute

  • ISSN

    0027-8874

  • e-ISSN

    1460-2105

  • Volume of the periodical

    114

  • Issue of the periodical within the volume

    5

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    13

  • Pages from-to

    740-752

  • UT code for WoS article

    000761987300001

  • EID of the result in the Scopus database

    2-s2.0-85129658097