SOD2 rs4880 CT/CC genotype predicts poor survival for Chinese gastric cancer patients received platinum and fluorouracil based adjuvant chemotherapy

Abstract

Adjuvant chemotherapy is a standard therapy for gastric cancer patients, however, treatment response is quite heterogeneous. Molecular biomarkers will be highly valuable to guide the therapy and predict the response and prognosis in these patients. The antioxidant enzymes superoxide dismutase 2 (SOD2) and glutathione S-transferase pi 1 (GSTP1) are involved in oxidative stress and drug detoxification, which modulate the efficacy of anticancer drugs. Here, we investigated the clinical associations of two functional single nucleotide polymorphisms of SOD2 and GSTP1 in stage II-III postoperative gastric cancer patients. SOD2 rs4880 and GSTP1 rs1695 were genotyped in 207 patients received postoperative platinum and fluorouracil based chemotherapy and 304 patients who did not. SOD2 rs4880 CT/CC significantly associated with decreased median overall survival time of 23 months when compared to the TT genotype (mean overall survival time of 65.2 months, P=0.002) only for patients received adjuvant chemotherapy. Stratification analysis showed SOD2 rs4880 CT/CC affected most significantly the clinical outcome for patients with tumor arising at gastric body (HR, 5.707, P=0.002), well to moderately differentiated adenocarcinoma (HR, 4.900, P<0.001), tumor of intestinal type (HR, 4.398, P<0.001), or tumor size less or equal to 5 cm (HR, 2.490, P=0.004); while GSTP1 rs1695 GA/GG was significant decreased overall survival time among patients with tumor arising at fundus or cardia (HR, 3.001, P=0.004), or mucinous or signet-ring cell carcinoma (HR, 4.750, P=0.042). The present study suggested the two polymorphisms would affect the adjuvant chemotherapy outcome in specific subtype of gastric cancer. SOD2 rs4880 could be used as a biomarker to predict the prognosis and response to therapy.

Keywords: Adjuvant chemotherapy; gastric cancer; glutathione s-transferase PI 1; prognosis; single nucleotide polymorphism; superoxide dismutase 2.

Figure 1

Kaplan-Meier survival curves of SOD2 rs4880 for overall survival in gastric cancer patients received adjuvant chemotherapy. A. SOD2 rs4880 CT/CC associated with poor overall survival in stage II patients. B. SOD2 rs4880 CT/CC associated with poor overall survival in stage III patients.