Effect of genetic polymorphisms related to DNA repair and the xenobiotic pathway on the prognosis and survival of gastric cancer patients

Background: A number of association studies have focused on the effect of polymorphisms related to DNA repair or the xenobiotic pathway, on the susceptibility to gastric cancer (GC). Here, the possible association between common polymorphisms in the X-ray repair cross-complementing groups (XRCC) 1, and glutathione-S-transferase (GST) genes and various clinicopathological characteristics, including overall survival, in GC patients were evaluated. Patients and Methods: XRCC1 Arg399Gln, and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were determined in 130 GC patients. Results: XRCC1 codon 194 Trp carriers (Trp/Trp + Arg/Trp) held a significantly higher risk of venous invasion (OR=3.76, 95%CI=1.05-13.51, p=0.043). A similar trend was also found for the XRCC1 codon 194 TrplTrp genotype (OR=2.15, 95% CI=0.87-5 34, p=0.099). The frequencies of the XRCC1 codon 399 Gln/Gln and Arg/Gln genotypes tended to be lower in lymphatic invasion-positive GC (XRCC1 codon 399 Gln/Gln: OR=0.27, 95% CI=0.06-1.15, p=0.075, Gln/Gln + Arg/Gln: OR=0.46, 95% CI=0.20-1.06, p=0.069), while the frequencies of the XRCC1 codon 194 Trp/Trp genotype tended to be higher in lymphatic invasion-positive GC (XRCC1 codon 194 Trp/Trp: OR=7.70, 95% CI=0.95-62.60, p=0.056). The patients with the GSTT1 null genotype showed significantly better overall survival than the patients with the GSTT1 present genotype (p=0.019). Conclusion: XRCC1 codon 194 Trp carrier status is correlated with more aggressive biological behavior of GC, such as venous invasion, and the GSTT1 null genotype is associated with better survival in GC patients.