TY - JOUR
T1 - Relevance of DNA repair gene polymorphisms to gastric cancer risk and phenotype
AU - Carrera-Lasfuentes, Patricia
AU - Lanas, Angel
AU - Bujanda, Luis
AU - Strunk, Mark
AU - Quintero, Enrique
AU - Santolaria, Santos
AU - Benito, Rafael
AU - Sopeña, Federico
AU - Piazuelo, Elena
AU - Thomson, Concha
AU - Pérez-Aisa, Angeles
AU - Nicolás-Pérez, David
AU - Hijona, Elizabeth
AU - Espinel, Jesús
AU - Campo, Rafael
AU - Manzano, Marisa
AU - Geijo, Fernando
AU - Pellise, Maria
AU - Zaballa, Manuel
AU - González-Huix, Ferrán
AU - Espinós, Jorge
AU - Titó, Llúcia
AU - Barranco, Luis
AU - D'Amato, Mauro
AU - García-González, María Asunción
PY - 2017
Y1 - 2017
N2 - Variations in DNA repair genes have been reported as key factors in gastric cancer (GC) susceptibility but results among studies are inconsistent. We aimed to assess the relevance of DNA repair gene polymorphisms and environmental factors to GC risk and phenotype in a Caucasian population in Spain. Genomic DNA from 603 patients with primary GC and 603 healthy controls was typed for 123 single nucleotide polymorphisms in DNA repair genes using the Illumina platform. Helicobacter pylori infection with CagA strains (odds ratio (OR): 1.99; 95% confidence interval (CI): 1.55–2.54), tobacco smoking (OR: 1.77; 95% CI: 1.22–2.57), and family history of GC (OR: 2.87; 95% CI: 1.85–4.45) were identified as independent risk factors for GC. By contrast, the TP53 rs9894946A (OR: 0.73; 95% CI: 0.56–0.96), TP53 rs1042522C (OR: 0.76; 95% CI: 0.56–0.96), and BRIP1 rs4986764T (OR: 0.55; 95% CI: 0.38–0.78) variants were associated with lower GC risk. Significant associations with specific anatomopathological GC subtypes were also observed, most notably in the ERCC4 gene with the rs1799801C, rs2238463G, and rs3136038T variants being inversely associated with cardia GC risk. Moreover, the XRCC3 rs861528 allele A was significantly increased in the patient subgroup with diffuse GC (OR: 1.75; 95% CI: 1.30–2.37). Our data show that specific TP53, BRIP1, ERCC4, and XRCC3 polymorphisms are relevant in susceptibility to GC risk and specific subtypes in Caucasians.
AB - Variations in DNA repair genes have been reported as key factors in gastric cancer (GC) susceptibility but results among studies are inconsistent. We aimed to assess the relevance of DNA repair gene polymorphisms and environmental factors to GC risk and phenotype in a Caucasian population in Spain. Genomic DNA from 603 patients with primary GC and 603 healthy controls was typed for 123 single nucleotide polymorphisms in DNA repair genes using the Illumina platform. Helicobacter pylori infection with CagA strains (odds ratio (OR): 1.99; 95% confidence interval (CI): 1.55–2.54), tobacco smoking (OR: 1.77; 95% CI: 1.22–2.57), and family history of GC (OR: 2.87; 95% CI: 1.85–4.45) were identified as independent risk factors for GC. By contrast, the TP53 rs9894946A (OR: 0.73; 95% CI: 0.56–0.96), TP53 rs1042522C (OR: 0.76; 95% CI: 0.56–0.96), and BRIP1 rs4986764T (OR: 0.55; 95% CI: 0.38–0.78) variants were associated with lower GC risk. Significant associations with specific anatomopathological GC subtypes were also observed, most notably in the ERCC4 gene with the rs1799801C, rs2238463G, and rs3136038T variants being inversely associated with cardia GC risk. Moreover, the XRCC3 rs861528 allele A was significantly increased in the patient subgroup with diffuse GC (OR: 1.75; 95% CI: 1.30–2.37). Our data show that specific TP53, BRIP1, ERCC4, and XRCC3 polymorphisms are relevant in susceptibility to GC risk and specific subtypes in Caucasians.
KW - gastric cancer
KW - Helicobacter pylori
KW - polymorphism
KW - DNA repair
U2 - 10.18632/oncotarget.16261
DO - 10.18632/oncotarget.16261
M3 - Article
SN - 1949-2553
VL - 8
SP - 35848
EP - 35862
JO - Oncotarget
JF - Oncotarget
IS - 22
ER -