Genome wide association identified colorectal cancer susceptibility loci and colorectal cancer risk in Lynch syndrome

Abstract

Background Recent genome-wide association studies (GWAS) have identified several common low-risk variants for colorectal cancer. Although some of the GWAS were enriched for young onset and family history positive colorectal cancer cases, it is not clear if these variants modify colorectal cancer risk for people with Lynch syndrome. In a case-unaffected sibling analysis of population and clinic based sibships, a study by Poynter et al. (2007) found a stronger association for risk variants in the 8q24 region (rs10505477 and rs6983627) with microsatellite instability (MSI)-high tumors. MSI-high tumors are characteristic of Lynch syndrome. Therefore we hypothesize that these variants may also influence colorectal cancer risk in Lynch syndrome. Recently Wijnen et al. (2009) have reported on some of the GWAS risk variants in Dutch Lynch syndrome families and although they did not find an association between rs6983627 and colorectal cancer risk, other risk variants in 8q24 and 9p24 have yet to be characterized in Lynch syndrome.