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Diabetes mellitus in relation to colorectal tumor molecular subtypes: a pooled analysis of more than 9000 cases
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.ORCID iD: 0000-0001-8540-6891
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).ORCID iD: 0000-0002-9692-101X
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.ORCID iD: 0000-0002-4688-8952
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2022 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 151, no 3, p. 348-360Article in journal (Refereed) Published
Abstract [en]

Diabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtypes could provide important insights into the biology of this association. We used data on lifestyle and clinical characteristics from the Colorectal Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), including 9756 colorectal cancer cases (with tumor marker data) and 9985 controls, to evaluate associations between reported diabetes and risk of colorectal cancer according to molecular subtypes. Tumor markers included BRAF and KRAS mutations, microsatellite instability and CpG island methylator phenotype. In the multinomial logistic regression model, comparing colorectal cancer cases to cancer-free controls, diabetes was positively associated with colorectal cancer regardless of subtype. The highest OR estimate was found for BRAF-mutated colorectal cancer, n = 1086 (ORfully adj: 1.67, 95% confidence intervals [CI]: 1.36-2.05), with an attenuated association observed between diabetes and colorectal cancer without BRAF-mutations, n = 7959 (ORfully adj: 1.33, 95% CI: 1.19-1.48). In the case only analysis, BRAF-mutation was differentially associated with diabetes (Pdifference = .03). For the other markers, associations with diabetes were similar across tumor subtypes. In conclusion, our study confirms the established association between diabetes and colorectal cancer risk, and suggests that it particularly increases the risk of BRAF-mutated tumors.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022. Vol. 151, no 3, p. 348-360
Keywords [en]
Colorectal Cancer, Diabetes, Subtype
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-193631DOI: 10.1002/ijc.34015ISI: 000784583000001PubMedID: 35383926Scopus ID: 2-s2.0-85129087573OAI: oai:DiVA.org:umu-193631DiVA, id: diva2:1650716
Funder
NIH (National Institutes of Health), P01 CA055075, P01 CA087969, R01 CA137178, R01 CA151993, R35 CA197735, R35 CA253185, U01 CA167551, U01 CA167552, UM1 CA186107Swedish Cancer SocietySwedish Research CouncilAvailable from: 2022-04-08 Created: 2022-04-08 Last updated: 2023-03-24Bibliographically approved

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Harlid, Sophiavan Guelpen, BethanyGylling, Björn

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