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

Abstract

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.

Gene–Diet Interactions in Colorectal Cancer: Survey Design, Instruments, Participants and Descriptive Data of a Case–Control Study in the Basque Country

“…Regarding the susceptibility SNPs for CRC, after an updated summary of the published SNPs [71,72], 48 previously reported CRC-susceptibility SNPs were selected and analyzed. The results of these SNPs were described in the manuscript of Alegria-Lertxundi et al [27]. In summary, we have confirmed a CRC susceptibility locus and the existence of associations between modifiable factors and the rs6687758 SNP; moreover, the genetic risk score (GRS) was associated with CRC.…”

“…In those cases for which there was more than one control per case, one was randomly selected for analysis. Further details on recruitment and data collection have been described elsewhere [27].…”

“…Additionally, in both cases and controls, socio-economic level and health status (specifically health resource consumption) data were assessed with two indices that were obtained from the clinical databases developed by the Health Department of the Basque Government, namely the socioeconomic deprivation index (DI) and predictive risk modeling (PRM), respectively. The first one was estimated using the MEDEA project criteria [66], as has been described elsewhere [27], and was divided into quintiles (Q), with the first being the least disadvantaged and the fifth being the most disadvantaged. The DI was successfully assigned to 80.2% of participants, while the quality of the registered information did not permit the linking of the remaining 19.8%.…”

Food groups, diet quality and colorectal cancer risk in the Basque Country

“…Finally, the matched case-to-control ratio was 1:1, and the final data set included 308 cases who were diagnosed with CRC and 308 age- and sex-matched controls. Further details on recruitment and data collection have been described elsewhere[ 15 ]. The main advantage of the present study compared to other above-mentioned researches[ 12 - 14 ] is that we confirmed that controls were free of the disease through colonoscopy.…”

“…Assistance from the study staff was available to help the patients to understand the items on the questionnaires. The quality management applied in the present study has been described in a previous article[ 15 ].…”