Single nucleotide polymorphisms associated with susceptibility for development of colorectal cancer: Case-control study in a Basque population
Autoři:
Iker Alegria-Lertxundi aff001; Carmelo Aguirre aff002; Luis Bujanda aff004; Francisco Javier Fernández aff005; Francisco Polo aff006; José M. Ordovás aff007; M. Carmen Etxezarraga aff010; Iñaki Zabalza aff012; Mikel Larzabal aff013; Isabel Portillo aff014; Marian M. de Pancorbo aff002; Leire Palencia-Madrid aff002; Ana M. Rocandio aff001; Marta Arroyo-Izaga aff001
Působiště autorů:
Department of Pharmacy and Food Sciences, Faculty of Pharmacy, University of the Basque Country, UPV/EHU, Vitoria-Gasteiz, Spain
aff001; BIOMICs Research Group, University of the Basque Country, UPV/EHU, Vitoria-Gasteiz, Spain
aff002; Pharmacovigilance Unit, Galdakao-Usansolo Hospital, Osakidetza, Spain
aff003; Department of Gastroenterology, Donostia University Hospital / BioDonostia Institute, Biomedicine Research Networking Center - CIBER of Hepatic and Digestive Diseases (CIBERehd), University of the Basque Country, UPV/EHU, San Sebastian, Spain
aff004; Department of Gastroenterology, Galdakao-Usansolo Hospital, Osakidetza, Galdakao, Spain
aff005; Department of Gastroenterology, Basurto University Hospital, Osakidetza, Bilbao, Spain
aff006; Nutrition and Genomics Laboratory, Jean Mayer Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, United States of America
aff007; IMDEA Food, Madrid, Spain
aff008; Nutritional Genomics and Epigenomics Group, Madrid Institute for Advanced Studies (IMDEA) Food Institute, Madrid, Spain
aff009; Department of Pathology, Basurto Hospital, Osakidetza, Bilbao, Spain
aff010; Department of Physician and Surgeon Specialities, University of the Basque Country, Leioa, UPV/EHU, Spain
aff011; Department of Pathology, Galdakao-Usansolo Hospital, Osakidetza, Galdakao, Spain
aff012; Department of Pathology, Donostia University Hospital / BioDonostia Institute, Biomedicine Research Networking Center - CIBER of Hepatic and Digestive Diseases (CIBERehd), San Sebastian, Spain
aff013; Colorectal Cancer Screening Programme, The Basque Health Service, Bilbao, Spain
aff014
Vyšlo v časopise:
PLoS ONE 14(12)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0225779
Souhrn
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.
Klíčová slova:
Alcohol consumption – Colorectal cancer – Gene expression – Genetic loci – Introns – Molecular genetics – Physical activity – Variant genotypes
Zdroje
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