Clinical significance of SOD2 and GSTP1 gene polymorphisms in Chinese patients with gastric cancer

Abstract

BACKGROUND: Excessive reactive oxygen species (ROS) accumulation is a common phenomenon in carcinogenesis. However, the rationale behind ROS involvement in gastric cancer is unclear. In this study, the authors investigated the clinical significance of the single nucleotide polymorphisms (SNPs) of 2 ROS metabolic process-related genes: superoxide dismutase 2 (SOD2) and glutathione Stransferase p (GSTP1). METHODS: In total of 929 patients with gastric cancer who had definitive clinicopathologic and follow-up data were collected. SOD2 reference SNP 4880 (rs4880) and GSTP1 rs1695 genotyping were examined in DNA samples extracted from paraffin-embedded tumor tissue. Association of the 2 SNPs with each clinicopathologic feature was analyzed using the Pearson chisquare test and the independent Student t test. Gastric cancer-specific overall survival was analyzed using Kaplan-Meier curves and log-rank tests. Multivariate Cox regression analyses of these SNPs also were performed. RESULTS: The SOD2 rs4880 CT þ CC genotypes were significantly associated with a high level of lymph node metastasis (P ¼ .023), whereas the GSTP1 rs1695 GA þ GG genotypes were significantly associated with larger tumor size (>5 cm long; P ¼ .048). Kaplan-Meier and Cox regression data indicated that the SOD2 rs4880 CT þ CC genotypes alone (hazard ratio, 1.299; 95% confidence interval, 1.053-1.603; P ¼ .015) and the GSTP1 rs1695 GA þ GG combined genotypes (hazard ratio, 1.496; 95% CI, 1.078-2.074; P ¼ .016) were independent predictors for overall survival. CONCLUSIONS: The current data, based on a large cohort (n ¼ 929) of Chinese patients with gastric cancer, suggested that the presence of SOD2 rs4880 and GSTP1 rs1695 genotypes may contribute to cancer progression as well as tumor aggressiveness. The components of ROS metabolism pathways may be potential therapeutic targets for this aggressive malignancy.

Dideoxy single allele-specific PCR - DSASP new method to discrimination allelic

“…However, García-González et al (2012), who studied the SNP rs1695 in 557 patients originating from southern Europe as GC, observed no association of this SNP with susceptibility to gastric cancer in this population (García-González et al 2012). The analysis of SNP rs1695 in 60 samples of GC patients from Northern Brazil by ASP method showed a positive association between the polymorphism in question and the development of intestinal-type gastric cancer, corroborating the findings of Xu et al (2012) and Araújo et al (2014). The same samples analyzed by Araújo et al (2014) using the ASP method were used to validate the DSASP method.…”

“…Haplotype SNPs rs1695, rs4891, rs762803 and rs749174 of the GSTP1 gene exhibited an association with lung cancer susceptibility in smokers in the overall population and in the studied subgroups but not the MPO SNP rs7208693 (Gu et al 2014). Xu et al (2012) studied 929 diagnostic GC patients in China and found a positive association between the SNPs rs1695 of the GSTP1 gene and rs4880 of the SOD2 gene to gastric carcinogenesis in this population. However, García-González et al (2012), who studied the SNP rs1695 in 557 patients originating from southern Europe as GC, observed no association of this SNP with susceptibility to gastric cancer in this population (García-González et al 2012).…”

Glutathione S-transferase A1 mediates nicotine-induced lung cancer cell metastasis by promoting epithelial-mesenchymal transition

“…Polymorphisms associated with the altered expression of these genes may affect the metabolism of carcinogens and chemotherapeutic agents (23), resulting in an increased risk of various malignances (24)(25)(26)(27)(28)(29)(30). Previous studies have demonstrated that GSTA1 overexpression protects tumor cells from doxorubicin and reactive oxygen species-induced apoptosis (31)(32)(33)(34).…”

Lack of Association Between Superoxide Dismutase Gene Polymorphism and Malignant Lymphoproliferative Disorders

“…The positive correlations between the polymorphisms and other kinds of cancers have been reported by previous researchers. For example, in recent studies on Chinese populations, the association between SOD2 polymorphisms and the risk of gastric cancer and its progression revealed a positive association (19,31). In contrast with the mentioned studies, there are several reports, which failed to confirm any association between SOD polymorphisms with the onset of malignancies.…”