863 Stool DNA Markers for the Detection of Neoplasia in Patients With Longstanding Inflammatory Bowel Disease

Introduction: First-degree relatives (FDR) of patients with colorectal cancer (CRC) have been shown to have a 2-to 3-fold increased risk of developing CRC compared with the overall population.It is likely that CRC susceptibility in these individuals results from common variants in low-penetrance genes.Very little is known about the relevance of genetic variants in the development of colorectal adenomas according to the family history of CRC.Trying to address this issue we carried out a case-control study comprising 750 FDR of patients with nonsyndromic CRC (cases), and 750 sex-aged-and histological lesion-matched individuals with no family history of CRC (controls).We aimed to evaluate the role of certain SNPs associated with CRC risk in the development of adenomas and family history of CRC.Methods: Cases and controls were selected from the Spanish CRC screening registries in Aragon and The Canary Islands.All subjects underwent at least one colonoscopy and diagnosis was confirmed by histological study.Genomic DNA from participants was genotyped by the MassArray™(Sequenom) platform for a panel of 99 SNPs previously associated with CRC risk.Results: Average age of participants was 54.5 +/-9.4 years with a slight predominance of women (51.7%).In 57% of patients, no preneoplastic lesions were found.By contrast, 288 patients (144 cases,144 controls) showed non advanced adenomas(NAA), and 354 patients (177cases,177controls) had advanced adenomas(AA).Concerning gene analysis, 2SNPs (rs10505477, rs6983267) located in the gen CASC8 were associated with the development of adenomas.Thus, the rs10505477G and the rs6983267T alleles were significantly associated with a reduced risk of adenomas in controls (log-additive models, OR:0.67, 95%CI:0.54-0.83,and OR:0.66, 95%CI:0.54-0.84,respectively).However, such a protective effect was not observed in cases.In the stratified analysis by histological lesion, the rs10505477G and the rs6983267T variants were significantly associated with a reduced risk of both, NAA and AA in controls, although this effect was stronger on the risk of developing NAA (OR:0.63,95%CI:0.47-0.84 for rs10505477, and OR:0.64, 95%CI:0.47-0.86 for rs6983267).Finally, 2 SNPs (rs10795668, rs11255841) located in the non-coding LINC00709 gene were significantly associated with a reduced risk of NAA in both, cases (recessive models, OR:0.22,95%CI:0.06-0.72 for rs10795668, and OR:0.08, 95%CI:0.03-0.61for rs11255841) and controls (dominant models, OR:0.50, 95%CI:0.34-0.75 for rs10795668G, and OR:0.52, 95%CI:0.35-0.78 for rs11255841), suggesting their possible implication in early stages of CRC development.Conclusions: Family history of CRC and some specific variants associated with CRC risk (rs10505477, rs6983267, rs10795668, and rs11255841) are involved in the development of colorectal adenomas or specific histological subtypes.