Genome-wide gene-environment interaction analyses to understand the relationship between red meat and processed meat intake and colorectal cancer risk.

BACKGROUND

High red meat and/or processed meat consumption are established colorectal cancer (CRC) 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 CRC 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 CRC risk (per quartile red meat OR = 1.30; 95%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 CRC.

IMPACT

The reported GxE interactions may explain the increased risk of CRC in certain population subgroups.