Journal Article

DKFZ-2020-00649

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk.

Xia, Z. ; Su, Y.-R. ; Petersen, P. ; Qi, L. ; Kim, A. E. ; }, , USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. ; Figueiredo, J. C. ; }, , USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. | Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. ; Lin, Y. ; Nan, H. ; Sakoda, L. C. ; Albanes, D. ; Berndt, S. I. ; Bézieau, S. ; Bien, S. ; Buchanan, D. D. ; Casey, G. ; Chan, A. T. ; Conti, D. V. ; }, , USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. ; Drew, D. A. ; Gallinger, S. J. ; Gauderman, W. J. ; }, , USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. ; Giles, G. G. ; Gruber, S. B. ; }, , USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. ; Gunter, M. J. ; Hoffmeister, M.DKFZ* ; Jenkins, M. A. ; Joshi, A. D. ; Le Marchand, L. ; Lewinger, J. P. ; }, , USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. ; Li, L. ; Lindor, N. M. ; Moreno, V. ; Murphy, N. ; Nassir, R. ; Newcomb, P. A. ; Ogino, S. ; Rennert, G. ; Song, M. ; Wang, X. ; Wolk, A. ; Woods, M. O. ; Brenner, H.DKFZ* ; White, E. ; Slattery, M. L. ; Giovannucci, E. L. ; Chang-Claude, J.DKFZ* ; Pharoah, P. D. P. ; Hsu, L. ; Campbell, P. T. ; Peters, U.

2020
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/cam4.2971

Abstract: Body mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology.To improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR <0.2.Among 4839 genes tested, genetically predicted expressions of FOXA1 (P = 3.15 × 10-5 ), PSMC5 (P = 4.51 × 10-4 ) and CD33 (P = 2.71 × 10-4 ) modified the association of BMI on CRC risk for men; KIAA0753 (P = 2.29 × 10-5 ) and SCN1B (P = 2.76 × 10-4 ) modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes (P = 2.31 × 10-5 ).Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.

Note: 2020 May;9(10):3563-3573

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Contributing Institute(s):

1. C070 Klinische Epidemiologie und Alternf. (C070)
2. Präventive Onkologie (C120)
3. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2020

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Database coverage:
; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DOAJ Seal ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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