Faculty, Staff and Student Publications

Publication Date

3-1-2024

Journal

Cancer Epidemiology, Biomarkers & Prevention

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: We propose two novel biomarkers that support the role of meat consumption with an increased risk of colorectal cancer.

Impact: The reported GxE interactions may explain the increased risk of colorectal cancer in certain population subgroups.

Keywords

Humans, Gene-Environment Interaction, Red Meat, Meat, Risk Factors, Colorectal Neoplasms

DOI

10.1158/1055-9965.EPI-23-0717

PMID

38112776

PMCID

PMC11343583

PubMedCentral® Posted Date

9-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

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