Single nucleotide polymorphisms associated with susceptibility for development of colorectal cancer: Case-control study in a Basque population

Given the significant population diversity in genetic variation, we aimed to investigate whether single nucleotide polymorphisms (SNPs) previously identified in studies of colorectal cancer (CRC) susceptibility were also relevant to the population of the Basque Country (North of Spain). We genotyped 230 CRC cases and 230 healthy controls for 48 previously reported CRC-susceptibility SNPs. Only the rs6687758 in DUPS10 exhibited a statistically significant association with CRC risk based on the crude analysis. The rs6687758 AG genotype conferred about 2.13-fold increased risk for CRC compared to the AA genotype. Moreover, we found significant associations in cases between smoking status, physical activity, and the rs6687758 SNP. The results of a Genetic Risk Score (GRS) showed that the risk alleles were more frequent in cases than controls and the score was associated with CRC in crude analysis. In conclusion, we have confirmed a CRC susceptibility locus and the existence of associations between modifiable factors and the rs6687758 SNP; moreover, the GRS was associated with CRC. However, further experimental validations are needed to establish the role of this SNP, the function of the gene identified, as well as the contribution of the interaction between environmental factors and this locusto the risk of CRC.This work was supported by two projects (from the Department of Health and Consumer Affairs, Basque Government 2011111153; and Saiotek, Basque Government S-PE12UN058), by a pre-doctoral grant from the Basque Government (PRE_2016_2_0046), by the CIBERehd and by the U.S. Department of Agriculture-Agricultural Research Service (ARS), under agreement. 581950-4-003. Neither Basque Government nor U.S. Department of Agriculture-Agricultural Research Service (ARS) had a role in the design, analysis or writing of this article. CIBERehd is funded by the Instituto de Salud Carlos III