Journal Article

DKFZ-2023-01283

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Probing the diabetes and colorectal cancer relationship using gene - environment interaction analyses.

Dimou, N. ; Kim, A. E. ; Flanagan, O. ; Murphy, N. ; Diez-Obrero, V. ; Shcherbina, A. ; Aglago, E. K. ; Bouras, E. ; Campbell, P. T. ; Casey, G. ; Gallinger, S. ; Gruber, S. B. ; Jenkins, M. A. ; Lin, Y. ; Moreno, V. ; Ruiz-Narvaez, E. ; Stern, M. C. ; Tian, Y.DKFZ* ; Tsilidis, K. K. ; Arndt, V.DKFZ* ; Barry, E. L. ; Baurley, J. W. ; Berndt, S. I. ; Bézieau, S. ; Bien, S. A. ; Bishop, D. T. ; Brenner, H.DKFZ* ; Budiarto, A. ; Carreras-Torres, R. ; Cenggoro, T. W. ; Chan, A. T. ; Chang-Claude, J.DKFZ* ; Chanock, S. J. ; Chen, X.DKFZ* ; Conti, D. V. ; Dampier, C. H. ; Devall, M. ; Drew, D. A. ; Figueiredo, J. C. ; Giles, G. G. ; Gsur, A. ; Harrison, T. A. ; Hidaka, A. ; Hoffmeister, M.DKFZ* ; Huyghe, J. R. ; Jordahl, K. ; Kawaguchi, E. ; Keku, T. O. ; Larsson, S. C. ; Le Marchand, L. ; Lewinger, J. P. ; Li, L. ; Mahesworo, B. ; Morrison, J. ; Newcomb, P. A. ; Newton, C. C. ; Obon-Santacana, M. ; Ose, J. ; Pai, R. K. ; Palmer, J. R. ; Papadimitriou, N. ; Pardamean, B. ; Peoples, A. R. ; Pharoah, P. D. P. ; Platz, E. A. ; Potter, J. D. ; Rennert, G. ; Scacheri, P. C. ; Schoen, R. E. ; Su, Y.-R. ; Tangen, C. M. ; Thibodeau, S. N. ; Thomas, D. C. ; Ulrich, C. M. ; Um, C. Y. ; van Duijnhoven, F. J. B. ; Visvanathan, K. ; Vodicka, P. ; Vodickova, L. ; White, E. ; Wolk, A. ; Woods, M. O. ; Qu, C. ; Kundaje, A. ; Hsu, L. ; Gauderman, W. J. ; Gunter, M. J. ; Peters, U.

2023
Nature Publ. Group Edinburgh

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Please use a persistent id in citations: doi:10.1038/s41416-023-02312-z

Abstract: 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.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).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).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.

Note: 2023 Aug;129(3):511-520

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)
2. C070 Klinische Epidemiologie und Alternf. (C070)
3. Präventive Onkologie (C120)
4. DKTK HD zentral (HD01)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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