{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:15:45Z","timestamp":1789672545290,"version":"4.0.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C18281\/A29019"],"award-info":[{"award-number":["C18281\/A29019"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glycemic traits\u2014such as hyperinsulinemia, hyperglycemia, and type 2 diabetes\u2014have 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Genome-wide association study summary data were used to identify genetic variants associated with circulating levels of fasting insulin (n\u2009=\u200934), 2-hour glucose (n\u2009=\u200913), fasting glucose (n\u2009=\u200970), HbA1c (n\u2009=\u2009221), and type 2 diabetes (n\u2009=\u2009268). Using 2-sample MR, we examined these variants in relation to colorectal cancer risk (48\u2009214 case patient and 64\u2009159 control patients).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In inverse-variance models, higher fasting insulin levels increased colorectal cancer risk (odds ratio [OR] per 1-SD\u2009=\u20091.65, 95% confidence interval [CI]\u2009=\u20091.15 to 2.36). We found no evidence of any effect of 2-hour glucose (OR per 1-SD\u2009=\u20091.02, 95% CI\u2009=\u20090.86 to 1.21) or fasting glucose (OR per 1-SD\u2009=\u20091.04, 95% CI\u2009=\u20090.88 to 1.23) concentrations on colorectal cancer risk. Genetic liability to type 2 diabetes (OR per 1-unit increase in log odds\u2009=\u20091.04, 95% CI\u2009=\u20091.01 to 1.07) and higher HbA1c levels (OR per 1-SD\u2009=\u20091.09, 95% CI\u2009=\u20091.00 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\u2009=\u20091.21, 95% CI\u2009=\u20091.05 to 1.40), but not in women.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djac011","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T07:07:44Z","timestamp":1642144064000},"page":"740-752","source":"Crossref","is-referenced-by-count":95,"title":["Associations Between Glycemic Traits and Colorectal Cancer: A Mendelian Randomization Analysis"],"prefix":"10.1093","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3347-8249","authenticated-orcid":false,"given":"Neil","family":"Murphy","sequence":"first","affiliation":[{"name":"Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1324-0316","authenticated-orcid":false,"given":"Mingyang","family":"Song","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA"},{"name":"Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA"},{"name":"Department of Epidemiology, Harvard T.H. 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