Journal Article

DKFZ-2022-00763

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region.

Jordahl, K. M. ; Shcherbina, A. ; Kim, A. E. ; Su, Y.-R. ; Lin, Y. ; Wang, J. ; Qu, C. ; Albanes, D. ; Arndt, V.DKFZ* ; Baurley, J. W. ; Berndt, S. I. ; Bien, S. A. ; Bishop, D. T. ; Bouras, E. ; Brenner, H.DKFZ* ; Buchanan, D. D. ; Budiarto, A. ; Campbell, P. T. ; Carreras-Torres, R. ; Casey, G. ; Cenggoro, T. W. ; Chan, A. T. ; Conti, D. V. ; Dampier, C. H. ; Devall, M. A. ; Díez-Obrero, V. ; Dimou, N. ; Drew, D. A. ; Figueiredo, J. C. ; Gallinger, S. ; Giles, G. G. ; Gruber, S. B. ; Gsur, A. ; Gunter, M. J. ; Hampel, H. ; Harlid, S. ; Harrison, T. A. ; Hidaka, A. ; Hoffmeister, M.DKFZ* ; Huyghe, J. R. ; Jenkins, M. A. ; Joshi, A. D. ; Keku, T. O. ; Larsson, S. C. ; Le Marchand, L. ; Lewinger, J. P. ; Li, L. ; Mahesworo, B. ; Moreno, V. ; Morrison, J. L. ; Murphy, N. ; Nan, H. ; Nassir, R. ; Newcomb, P. A. ; Obón-Santacana, M. ; Ogino, S. ; 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. ; Prentice, R. L. ; Rennert, G. ; Ruiz-Narvaez, E. ; Sakoda, L. C. ; Scacheri, P. C. ; Schmit, S. L. ; Schoen, R. E. ; Slattery, M. L. ; Stern, M. C. ; Tangen, C. M. ; Thibodeau, S. N. ; Thomas, D. C. ; Tian, Y.DKFZ* ; Tsilidis, K. K. ; Ulrich, C. M. ; van Duijnhoven, F. J. B. ; Van Guelpen, B. ; Visvanathan, K. ; Vodicka, P. ; White, E. ; Wolk, A. ; Woods, M. O. ; Wu, A. H. ; Zemlianskaia, N. ; Chang-Claude, J.DKFZ* ; Gauderman, W. J. ; Hsu, L. ; Kundaje, A. ; Peters, U.

2022
AACR Philadelphia, Pa.

This record in other databases:  

Please use a persistent id in citations: doi:10.1158/1055-9965.EPI-21-1003

Abstract: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer.Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1-28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models.For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose-response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06-1.17; OR for AA genotype = 1.22; 95% CI, 1.14-1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif.Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region.The study identifies multifaceted evidence of a possible functional effect for rs1318920.

Note: 2022 May 4;31(5):1077-1089

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Contributing Institute(s):

1. C071 Cancer Survivorship (C071)
2. C070 Klinische Epidemiologie und Alternf. (C070)
3. Präventive Onkologie (C120)
4. DKTK HD zentral (HD01)
5. C020 Epidemiologie von Krebs (C020)

Research Program(s):

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

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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