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Probing the diabetes and colorectal cancer relationship using gene – environment interaction analyses

Niki Dimou, Andre E. Kim, Orlagh Flanagan, Neil Murphy, Virginia Diez-Obrero, Anna Shcherbina, Elom K. Aglago, Emmanouil Bouras, Peter T. Campbell, Graham Casey, Steven Gallinger, Stephen B. Gruber, Mark A. Jenkins, Yi Lin, Victor Moreno, Edward Ruiz-Narvaez, Mariana C. Stern, Yu Tian, Kostas K. Tsilidis, Volker Arndt, Elizabeth L. Barry, James W. Baurley, Sonja I. Berndt, Stéphane Bézieau, Stephanie A. Bien, D. Timothy Bishop, Hermann Brenner, Arif Budiarto, Robert Carreras-Torres, Tjeng Wawan Cenggoro, Andrew T. Chan, Jenny Chang-Claude, Stephen J. Chanock, Xuechen Chen, David V. Conti, Christopher H. Dampier, Matthew Devall, David A. Drew, Jane C. Figueiredo, Graham G. Giles, Andrea Gsur, Tabitha A. Harrison, Akihisa Hidaka, Michael Hoffmeister, Jeroen R. Huyghe, Kristina Jordahl, Eric Kawaguchi, Temitope O. Keku, Susanna C. Larsson, Loic Le Marchand, Juan Pablo Lewinger, Li Li, Bharuno Mahesworo, John Morrison, Polly A. Newcomb, Christina C. Newton, Mireia Obon-Santacana, Jennifer Ose, Rish K. Pai, Julie R. Palmer, Nikos Papadimitriou, Bens Pardamean, Anita R. Peoples, Paul D. P. Pharoah, Elizabeth A. Platz, John D. Potter, Gad Rennert, Peter C. Scacheri, Robert E. Schoen, Yu-Ru Su, Catherine M. Tangen, Stephen N. Thibodeau, Duncan C. Thomas, Cornelia M. Ulrich, Caroline Y. Um, Fränzel J. B. van Duijnhoven, Kala Visvanathan, Pavel Vodicka, Ludmila Vodickova, Emily White, Alicja Wolk, Michael O. Woods, Conghui Qu, Anshul Kundaje, Li Hsu, W. James Gauderman, Marc J. Gunter, Ulrike Peters

  • Background: Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis. Methods: We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom; d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test). Results: Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177, SLC30A8 – ORAA: 1.62, 95% CI: 1.34–1.96; ORAG: 1.41, 95% CI: 1.30–1.54; ORGG: 1.22, 95% CI: 1.13–1.31; p-value3-d.f.: 5.46 × 10−11) and 13q14.13 (rs9526201, LRCH1 – ORGG: 2.11, 95% CI: 1.56–2.83; ORGA: 1.52, 95% CI: 1.38–1.68; ORAA: 1.13, 95% CI: 1.06–1.21; p-value2-d.f.: 7.84 × 10−09). Discussion: These results suggest that variation in genes related to insulin signaling (SLC30A8) and immune function (LRCH1) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.

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Author:Niki DimouORCiD, Andre E. Kim, Orlagh Flanagan, Neil MurphyORCiD, Virginia Diez-Obrero, Anna Shcherbina, Elom K. AglagoORCiD, Emmanouil BourasORCiD, Peter T. Campbell, Graham Casey, Steven Gallinger, Stephen B. Gruber, Mark A. Jenkins, Yi Lin, Victor MorenoORCiD, Edward Ruiz-NarvaezORCiD, Mariana C. Stern, Yu Tian, Kostas K. Tsilidis, Volker ArndtORCiD, Elizabeth L. Barry, James W. Baurley, Sonja I. Berndt, Stéphane Bézieau, Stephanie A. Bien, D. Timothy BishopORCiD, Hermann BrennerORCiD, Arif Budiarto, Robert Carreras-Torres, Tjeng Wawan Cenggoro, Andrew T. ChanORCiD, Jenny Chang-Claude, Stephen J. Chanock, Xuechen ChenORCiD, David V. Conti, Christopher H. Dampier, Matthew Devall, David A. Drew, Jane C. Figueiredo, Graham G. Giles, Andrea Gsur, Tabitha A. Harrison, Akihisa Hidaka, Michael HoffmeisterORCiD, Jeroen R. HuygheORCiD, Kristina Jordahl, Eric Kawaguchi, Temitope O. Keku, Susanna C. LarssonORCiD, Loic Le Marchand, Juan Pablo Lewinger, Li Li, Bharuno Mahesworo, John Morrison, Polly A. NewcombORCiD, Christina C. Newton, Mireia Obon-Santacana, Jennifer OseORCiDGND, Rish K. Pai, Julie R. PalmerORCiD, Nikos Papadimitriou, Bens Pardamean, Anita R. Peoples, Paul D. P. PharoahORCiD, Elizabeth A. Platz, John D. PotterORCiD, Gad Rennert, Peter C. Scacheri, Robert E. Schoen, Yu-Ru Su, Catherine M. Tangen, Stephen N. Thibodeau, Duncan C. Thomas, Cornelia M. Ulrich, Caroline Y. UmORCiD, Fränzel J. B. van Duijnhoven, Kala VisvanathanORCiD, Pavel Vodicka, Ludmila Vodickova, Emily White, Alicja WolkORCiD, Michael O. Woods, Conghui Qu, Anshul KundajeORCiD, Li Hsu, W. James Gauderman, Marc J. Gunter, Ulrike Peters
URN:urn:nbn:de:bsz:960-opus4-31525
DOI:https://doi.org/10.25968/opus-3152
DOI original:https://doi.org/10.1038/s41416-023-02312-z
ISSN:1532-1827
Parent Title (English):British Journal of Cancer
Document Type:Article
Language:English
Year of Completion:2023
Publishing Institution:Hochschule Hannover
Release Date:2024/06/10
Tag:Cancer genetics; Colon cancer
GND Keyword:Dickdarmkrebs; Diabetes mellitus Typ 2; Krebsrisiko
Volume:129
First Page:511
Last Page:520
Institutes:Fakultät III - Medien, Information und Design
DDC classes:610 Medizin, Gesundheit
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International