Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region

Kristina M Jordahl; Anna Shcherbina; Andre E Kim; Yu-Ru Su; Yi Lin; Jun Wang; Conghui Qu; Demetrius Albanes; Volker Arndt; James W Baurley; Sonja I Berndt; Stephanie A Bien; D Timothy Bishop; Emmanouil Bouras; Hermann Brenner; Daniel D Buchanan; Arif Budiarto; Peter T Campbell; Robert Carreras-Torres; Graham Casey; Tjeng Wawan Cenggoro; Andrew T Chan; David V Conti; Christopher H Dampier; Matthew A Devall; Virginia Díez-Obrero; Niki Dimou; David A Drew; Jane C Figueiredo; Steven Gallinger; Graham G Giles; Stephen B Gruber; Andrea Gsur; Marc J Gunter; Heather Hampel; Sophia Harlid; Tabitha A Harrison; Akihisa Hidaka; Michael Hoffmeister; Jeroen R Huyghe; Mark A Jenkins; Amit D Joshi; Temitope O Keku; Susanna C Larsson; Loic Le Marchand; Juan Pablo Lewinger; Li Li; Bharuno Mahesworo; Victor Moreno; John L Morrison; Neil Murphy; Hongmei Nan; Rami Nassir; Polly A Newcomb; Mireia Obón-Santacana; Shuji Ogino; 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; Ross L Prentice; Gad Rennert; Edward Ruiz-Narvaez; Lori C Sakoda; Peter C Scacheri; Stephanie L Schmit; Robert E Schoen; Martha L Slattery; Mariana C Stern; Catherine M Tangen; Stephen N Thibodeau; Duncan C Thomas; Yu Tian; Konstantinos K Tsilidis; Cornelia M Ulrich; Franzel J B van Duijnhoven; Bethany Van Guelpen; Kala Visvanathan; Pavel Vodicka; Emily White; Alicja Wolk; Michael O Woods; Anna H Wu; Natalia Zemlianskaia; Jenny Chang-Claude; W James Gauderman; Li Hsu; Anshul Kundaje; Ulrike Peters

doi:10.1158/1055-9965.EPI-21-1003

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Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region

Journal article

Peer reviewed

Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region

Kristina M Jordahl, Anna Shcherbina, Andre E Kim, Yu-Ru Su, Yi Lin, Jun Wang, Conghui Qu, Demetrius Albanes, Volker Arndt, James W Baurley, …

Cancer epidemiology, biomarkers & prevention, Vol.31(5), pp.1077-1089

04/05/2022

DOI: https://doi.org/10.1158/1055-9965.EPI-21-1003

PMID: 35438744

Abstract

Alcohol Drinking - adverse effects

Alcohol Drinking - epidemiology

Alcohol Drinking - genetics

Colorectal Neoplasms - etiology

Colorectal Neoplasms - genetics

Electron Transport Complex IV - genetics

Genome-Wide Association Study

Humans

Polymorphism, Single Nucleotide

Risk Factors

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.

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Title: Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region
Creators - without role: Kristina M Jordahl - University of Washington
Anna Shcherbina - Stanford University
Andre E Kim - University of Southern California
Yu-Ru Su - Fred Hutch Cancer Center
Yi Lin - Fred Hutch Cancer Center
Jun Wang - University of Southern California
Conghui Qu - Fred Hutch Cancer Center
Demetrius Albanes - National Cancer Institute
Volker Arndt - German Cancer Research Center
James W Baurley - Binus University
Sonja I Berndt - National Cancer Institute
Stephanie A Bien - Fred Hutch Cancer Center
D Timothy Bishop - University of Leeds
Emmanouil Bouras - University of Ioannina
Hermann Brenner - German Cancer Research Center
Daniel D Buchanan - University of Melbourne
Arif Budiarto - Binus University
Peter T Campbell - Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia
Robert Carreras-Torres - Bellvitge University Hospital
Graham Casey - University of Virginia
Tjeng Wawan Cenggoro - Binus University
Andrew T Chan - Brigham and Women's Hospital
David V Conti - University of Southern California
Christopher H Dampier - University of Virginia
Matthew A Devall - University of Virginia
Virginia Díez-Obrero - Bellvitge University Hospital
Niki Dimou - International Agency For Research On Cancer
David A Drew - Massachusetts General Hospital
Jane C Figueiredo - University of Southern California
Steven Gallinger - University of Toronto
Graham G Giles - Cancer Council Victoria
Stephen B Gruber - University of Southern California
Andrea Gsur - Medical University of Vienna
Marc J Gunter - International Agency For Research On Cancer
Heather Hampel - The Ohio State University
Sophia Harlid - Umeå University
Tabitha A Harrison - Fred Hutch Cancer Center
Akihisa Hidaka - Fred Hutch Cancer Center
Michael Hoffmeister - German Cancer Research Center
Jeroen R Huyghe - Fred Hutch Cancer Center
Mark A Jenkins - University of Melbourne
Amit D Joshi - Harvard University
Temitope O Keku - University of North Carolina at Chapel Hill
Susanna C Larsson - Karolinska Institutet
Loic Le Marchand - University of Hawaii System
Juan Pablo Lewinger - University of Southern California
Li Li - University of Virginia
Bharuno Mahesworo - Binus University
Victor Moreno - Institut d'Investigació Biomédica de Bellvitge
John L Morrison - Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
Neil Murphy - International Agency For Research On Cancer
Hongmei Nan - Richard M. Fairbanks Foundation
Rami Nassir - Umm al-Qura University
Polly A Newcomb - University of Washington
Mireia Obón-Santacana - Institut Català d'Oncologia
Shuji Ogino - Harvard University
Jennifer Ose - Huntsman Cancer Institute
Rish K Pai - Mayo Clinic
Julie R Palmer - Boston University
Nikos Papadimitriou - International Agency For Research On Cancer
Bens Pardamean - Binus University
Anita R Peoples - Huntsman Cancer Institute
Paul D P Pharoah - University of Cambridge
Elizabeth A Platz - Bloomberg
John D Potter - Fred Hutch Cancer Center
Ross L Prentice - Fred Hutch Cancer Center
Gad Rennert - Carmel Medical Center
Edward Ruiz-Narvaez - University of Michigan–Ann Arbor
Lori C Sakoda - Fred Hutch Cancer Center
Peter C Scacheri - Case Western Reserve University
Stephanie L Schmit - Cleveland Clinic
Robert E Schoen - University of Pittsburgh Medical Center
Martha L Slattery - University of Utah
Mariana C Stern - University of Southern California
Catherine M Tangen - Fred Hutch Cancer Center
Stephen N Thibodeau - Mayo Clinic
Duncan C Thomas - University of Southern California
Yu Tian - German Cancer Research Center
Konstantinos K Tsilidis - Imperial College London
Cornelia M Ulrich - Huntsman Cancer Institute
Franzel J B van Duijnhoven - Wageningen University & Research
Bethany Van Guelpen - Umeå University
Kala Visvanathan - Bloomberg
Pavel Vodicka - Charles University
Emily White - Fred Hutch Cancer Center
Alicja Wolk - Karolinska Institutet
Michael O Woods - Memorial University of Newfoundland
Anna H Wu - University of Southern California
Natalia Zemlianskaia - University of Southern California
Jenny Chang-Claude - German Cancer Research Center
W James Gauderman - University of Southern California
Li Hsu - Fred Hutch Cancer Center
Anshul Kundaje - Stanford University
Ulrike Peters - University of Washington
Publication Details: Cancer epidemiology, biomarkers & prevention, Vol.31(5), pp.1077-1089
Grant note: U01 CA206110 / NCI NIH HHS P30 ES010126 / NIEHS NIH HHS R01 CA201407 / NCI NIH HHS R01 CA059045 / NCI NIH HHS U01 CA182883 / NCI NIH HHS UG1 CA189974 / NCI NIH HHS U01 CA137088 / NCI NIH HHS R01 CA206279 / NCI NIH HHS U01 CA164930 / NCI NIH HHS
Identifiers: 9931657008331
Academic Unit: Umm Al Qura University
Language: English
Resource Type: Journal article