Genome-Wide Gene–Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk
AbstractBackground:. 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 G