A large multi-centre, multi-national research collaboration led by the Fred Hutchinson Cancer Research Center (Washington, US) and the National Human Genome Research Institute (Maryland, US) performed genome-wide interaction analysis using large data-sets from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) to identify candidate SNPs, and then followed-up with gene expression studies of identified genes in normal and cancerous tissues.
Colorectal cancer is the third-most common cancer in men and the second most common cancer in women worldwide. Since 2007, genome-wide association studies (GWAS) have identified only a small portion of the variants which account for CRC inheritance; researchers such as Gong, Hutter and the rest of the study contributors are turning to analysis of the interactions between genes and environmental risk factors (genome-wide interaction analysis) to find additional CRC risk variants.
Consistent with previous studies, the team observed an inverse association with CRC risk for light-to-moderate drinkers but a positive association for heavy drinkers compared with non-/occasional drinkers. Using conventional logistic regression, the team identified genome-wide significant interactions between 11 SNPs at the 9q22.32/HIATL1 locus and light-to-moderate drinking. The most significant SNP was rs9409565, located in an intergenic region 28kb downstream of HIATL1. All other 10 genome-wide significant SNPs were in strong linkage disequilibrium with rs9409565 and some located within HIATL1.
Gene expression analysis of HIATL1 indicated that the SNPs identified impacted HIATL1 expression, that HIATL1 Is involved in signalling pathways related to CRC, that HIATL1 expression differs between normal and tumor CR tissue and that HIATL1 expression in colon tissue differs by alcohol consumption.
Further replication and functional studies are required to confirm findings and understand the biologic implications of the interaction, and could provide further insight into CRC etiology, identifying potentially susceptible subpopulations.