Characterization of gene-environment interactions for colorectal cancer susceptibility loci.

Publication Type:

Journal Article


Cancer research, Volume 72, Issue 8, p.2036-44 (2012)


2012, Center-Authored Paper, Collaborative Data Services Core Facility, Consortium Authored Paper, Epidemiology Core Facility, Mar 2012, March 2012, Nutrition Assessment Core Facility, Public Health Sciences Division, Shared Resources, Specimen Processing Core Facility


Genome-wide association studies (GWAS) have identified over a dozen loci associated with colorectal cancer (CRC) risk. Here we examined potential effect-modification between single nucleotide polymorphisms (SNPs) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case-control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at 8q23.3 (EIF3H/UTP23); rs6983267 at 8q24 (MYC); rs10795668 at 10p14 (FLJ3802842); rs3802842 at11q23 (LOC120376); rs4444235 at 14q22.2 (BMP4); rs4779584 at15q13 (GREM1); rs9929218 at16q22.1 (CDH1); rs4939827 at18q21 (SMAD7); rs10411210 at19q13.1 (RHPN2); and rs961253 at 20p12.3 (BMP2)] and select major CRC risk factors (sex, body mass index, height, smoking status, aspirin/non-steroidal anti-inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red meat, processed meat, vegetables, fruit, and fiber). The strongest statistical evidence for a gene-environment interaction across studies was for vegetable consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and UTP23 genes (nominal p-interaction =1.3x10-4; adjusted p-value 0.02). The magnitude of the main effect of the SNP increased with increasing levels of vegetable consumption. No other interactions were statistically significant after adjusting for multiple comparisons. Overall, the association of most CRC susceptibility loci identified in initial GWAS appears to be invariant to the other risk factors considered; however, our results suggest potential modification of the rs16892766 effect by vegetable consumption.