PARP-1 Val762Ala polymorphism, CagA+ H. pylori infection and risk for gastric cancer in Han Chinese population

Mol Biol Rep. 2009 Jul;36(6):1461-7. doi: 10.1007/s11033-008-9336-y. Epub 2008 Aug 21.

Abstract

Introduction: PARP-1 plays important role in the BER (base excision repair) and maintenance of genomic integrity. Previous study found the Val762Ala genetic variant in the PARP-1 gene contributed to susceptibility of some cancers and decreased PARP-1 enzyme activity in response to oxidative damage. Helicobacter pylori (H. pylori) infection was thought to be one of the major causes of gastric cancer. In this study, we investigated the association between the PARP-1 Val762Ala polymorphism, CagA(+) H. pylori infection, and the risk for gastric cancer.

Methods: This hospital-based, case-control study was performed involving 556 individuals (236 cases with gastric cancer and 320 controls without evidence of neoplasm and gastrointestinal disease) using a PCR-RFLP method. Chi-square test and logistic regression analysis were used to count OR and 95% CI.

Results: 762Ala/Ala genotype was overrepresented in the cases (16.9%) compared with controls (10.3%), (OR, 1.942; 95% CI, 1.157-3.257, P = 0.011). Multivariate analysis showed that two factors were significantly associated with risk of gastric cancer, including CagA(+) H. pylori infection (OR, 2.562; 95% CI, 1.174-5.240, P = 0.037), PARP-1 762AA genotype (OR, 1.772; 95% CI, 1.065-3.867; P = 0.042). Stratification analysis indicated that among Cag(+) H. pylori positive subjects, 762Ala/Ala carriers had higher risk for developing gastric cancer compared with 762Val/Val carrier (OR, 2.337; 95% CI, 1.148-4.758; P = 0.017).

Conclusion: PARP-1 762Ala/Ala could be a risk factor for gastric cancer in Han Chinese population; PARP-1 762Val/Ala polymorphism and Cag(+) H. pylori infection jointly contribute to higher risk for gastric cancer.

MeSH terms

  • Amino Acid Substitution
  • Analysis of Variance
  • Case-Control Studies
  • China / epidemiology
  • Genetic Predisposition to Disease / epidemiology
  • Genotype
  • Helicobacter Infections / epidemiology
  • Helicobacter Infections / genetics*
  • Humans
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Risk
  • Stomach Neoplasms / epidemiology
  • Stomach Neoplasms / genetics*

Substances

  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases