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Supplementary Figure 4 from Genome-Wide Gene–Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk

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posted on 2024-03-01, 12:20 authored by Mariana C. Stern, Joel Sanchez Mendez, Andre E. Kim, Mireia Obón-Santacana, Ferran Moratalla-Navarro, Vicente Martín, Victor Moreno, Yi Lin, Stephanie A. Bien, Conghui Qu, Yu-Ru Su, Emily White, Tabitha A. Harrison, Jeroen R. Huyghe, Catherine M. Tangen, Polly A. Newcomb, Amanda I. Phipps, Claire E. Thomas, Eric S. Kawaguchi, Juan Pablo Lewinger, John L. Morrison, David V. Conti, Jun Wang, Duncan C. Thomas, Elizabeth A. Platz, Kala Visvanathan, Temitope O. Keku, Christina C. Newton, Caroline Y. Um, Anshul Kundaje, Anna Shcherbina, Neil Murphy, Marc J. Gunter, Niki Dimou, Nikos Papadimitriou, Stéphane Bézieau, Franzel J.B. van Duijnhoven, Satu Männistö, Gad Rennert, Alicja Wolk, Michael Hoffmeister, Hermann Brenner, Jenny Chang-Claude, Yu Tian, Loïc Le Marchand, Michelle Cotterchio, Konstantinos K. Tsilidis, D. Timothy Bishop, Yohannes Adama Melaku, Brigid M. Lynch, Daniel D. Buchanan, Cornelia M. Ulrich, Jennifer Ose, Anita R. Peoples, Andrew J. Pellatt, Li Li, Matthew A.M. Devall, Peter T. Campbell, Demetrius Albanes, Stephanie J. Weinstein, Sonja I. Berndt, Stephen B. Gruber, Edward Ruiz-Narvaez, Mingyang Song, Amit D. Joshi, David A. Drew, Jessica L. Petrick, Andrew T. Chan, Marios Giannakis, Ulrike Peters, Li Hsu, W. James Gauderman

Locus Zoom plots for the two polymorphisms reported in the genome-wide gene-interaction main results.

Funding

National Cancer Institute (NCI)

United States Department of Health and Human Services

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Conseil Régional des Pays de la Loire (Région Pays de la Loire)

Center for Strategic Scientific Initiatives, National Cancer Institute (CSSI, NCI)

National Institutes of Health (NIH)

Instituto de Salud Carlos III (ISCIII)

Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR)

Junta de Castilla y León (JCYL)

Fundación Científica Asociación Española Contra el Cáncer (AECC)

Deutsche Forschungsgemeinschaft (DFG)

Bundesministerium für Bildung und Forschung (BMBF)

Damon Runyon Cancer Research Foundation (DRCRF)

Cancer Research UK (CRUK)

American Cancer Society (ACS)

NIHR Imperial Biomedical Research Centre (BRC)

Cancer Council Victoria

Vetenskapsrådet (VR)

History

ARTICLE ABSTRACT

High red meat and/or processed meat consumption are established colorectal cancer risk factors. We conducted a genome-wide gene–environment (GxE) interaction analysis to identify genetic variants that may modify these associations. A pooled sample of 29,842 colorectal cancer cases and 39,635 controls of European ancestry from 27 studies were included. Quantiles for red meat and processed meat intake were constructed from harmonized questionnaire data. Genotyping arrays were imputed to the Haplotype Reference Consortium. Two-step EDGE and joint tests of GxE interaction were utilized in our genome-wide scan. Meta-analyses confirmed positive associations between increased consumption of red meat and processed meat with colorectal cancer risk [per quartile red meat OR = 1.30; 95% confidence interval (CI) = 1.21–1.41; processed meat OR = 1.40; 95% CI = 1.20–1.63]. Two significant genome-wide GxE interactions for red meat consumption were found. Joint GxE tests revealed the rs4871179 SNP in chromosome 8 (downstream of HAS2); greater than median of consumption ORs = 1.38 (95% CI = 1.29–1.46), 1.20 (95% CI = 1.12–1.27), and 1.07 (95% CI = 0.95–1.19) for CC, CG, and GG, respectively. The two-step EDGE method identified the rs35352860 SNP in chromosome 18 (SMAD7 intron); greater than median of consumption ORs = 1.18 (95% CI = 1.11–1.24), 1.35 (95% CI = 1.26–1.44), and 1.46 (95% CI = 1.26–1.69) for CC, CT, and TT, respectively. We propose two novel biomarkers that support the role of meat consumption with an increased risk of colorectal cancer. The reported GxE interactions may explain the increased risk of colorectal cancer in certain population subgroups.

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    Cancer Epidemiology, Biomarkers & Prevention

    Categories

    Keywords

    BiomarkersCancer risk biomarkersBiostatisticsEndogenous Risk FactorsGene polymorphismsGastrointestinal CancersColorectal cancerLifestyle Risk FactorsDiet

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    CC BY

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