Relevance of DNA repair gene polymorphisms to gastric cancer risk and phenotype

Patricia Carrera-Lasfuentes, Angel Lanas, Luis Bujanda, Mark Strunk, Enrique Quintero, Santos Santolaria, Rafael Benito, Federico Sopeña, Elena Piazuelo, Concha Thomson, Angeles Pérez-Aisa, David Nicolás-Pérez, Elizabeth Hijona, Jesús Espinel, Rafael Campo, Marisa Manzano, Fernando Geijo, Maria Pellise, Manuel Zaballa, Ferrán González-HuixJorge Espinós, Llúcia Titó, Luis Barranco, Mauro D'Amato, María Asunción García-González

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)35848-35862
Number of pages15
JournalOncotarget
Volume8
Issue number22
DOIs
Publication statusPublished - 2017
Externally publishedYes

Keywords

  • gastric cancer
  • Helicobacter pylori
  • polymorphism
  • DNA repair

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