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Objectives: Excessive reactive oxygen species (ROS) accumulation is a common phenomenon in carcinogenesis.However, the rationale behind ROS involved in gastric cancer is unclear.In this study we sought to investigate the clinical significance of the single nucleotide polymorphisms (SNPs) of two ROS metabolic process related genes,superoxide dismutase 2 (SOD2) and glutathione S-transferase Pi (GSTP1).Methods: A total of 929 gastric cancer patients with definitive clinicopathologic and follow-up data were collected.SOD2 rs4880 and GSTP1 rs1695 genotyping were examined from the DNA extracted from paraffin-embedded tumor tissue.Association of the two SNPs with each clinicopathologic feature was analyzed by Pearson s chi-square test and independent Student t-test.The gastric cancer-specific overall survival was analyzed by Kaplan-Meier curve and Log-rank test.Multivariate Cox regression analyses of these SNPs were also performed.Results: SOD2 rs4880 CT+CC genotypes were significantly associated with high regional lymph node metastasis (P=0.023), whilst GSTP1 rs1695 GA+GG genotypes significantly associated with larger tumor size (>5cm in length, P=0.048).Kaplan-Meier and Cox regression data indicated that SOD2 rs4880 CT+CC (HR, 1.299;95% CI, 1.053-1.603P=0.015) alone and the GSTP1 rs1695 GA+GG combined genotypes (HR, 1.496;95% CI, 1.078-2.074, P=0.016) were independent predictors for overall survival.Conclusions: Our data based on a large cohort (n=929) of Chinese gastric cancer patients suggests that the presence of SOD2 rs4880 and GSTP1 rs1695 genotypes might contribute to cancer progression as well as tumor aggressiveness.The components of ROS metabolism pathways may be potential therapeutic targets for this aggressive malignancy.