The Impact of GST Genetic Polymorphisms on the Response to Oxaliplatin-Based Chemotherapy and Survival Prognosis in Gastric Cancer Patients

Abstract Purpose The majority of gastric cancer (GC) cases are diagnosed at advanced stages, with chemotherapy serving as the primary treatment modality. However, the efficacy of this approach is significantly influenced by individual genetic variations. A nuanced understanding of genetic associations can aid in predicting treatment response and survival outcomes in patients. Consequently, this study seeks to investigate the relationship between polymorphisms in glutathione S-transferase (GST) family genes, specifically GSTP1, GSTM1, and GSTT1, and both survival rates and treatment response to oxaliplatin-based chemotherapy among GC patients in Northwest China. Patients and Methods: A total of 185 histologically confirmed GC cases were included in the study. All patients received either S-1 plus oxaliplatin (SOX) or oxaliplatin plus capecitabine (XELOX) chemotherapy regimen. GSTP1 genotypes were detected using PCR restriction fragment length polymorphism (PCRRFLP), while GSTM1 and GSTT1 genotypes were identified through multiplex PCR (M-PCR). The response to chemotherapy was evaluated based on the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) documented. Logistic regression analysis was employed to assess the relationship between genetic polymorphisms and chemotherapy response, and survival outcomes were estimated using the Kaplan-Meier method, with differences in survival rates analyzed via the log-rank test. Cox proportional hazard models were utilized to compute hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). Results Patients with GC carrying the GSTP1(AG + GG) genotype exhibited a significantly higher chemotherapy response rate compared to those with the GSTP1(AA) genotype (OR = 0.388, P = 0.028). Multivariate logistic regression analysis further substantiated that the GSTP1 (AG + GG) genotype was independently linked to an improved chemotherapy response (OR = 0.301, P = 0.021). Moreover, patients with the GSTP(AG + GG) genotype demonstrated a notably lower risk of disease progression (HR = 1.645, log-rank P = 0.003) and mortality (HR = 1.705, log-rank P = 0.007) relative to those with the AA genotype. In contrast, no significant associations were found between GSTM1 or GSTT1 gene polymorphisms and either the therapeutic response to chemotherapy or survival outcomes. However, a combined analysis of GSTP1(AG + GG) /GSTM1-genotypes revealed a statistically significant enhancement in chemotherapy response (OR = 6.000, P = 0.011). Furthermore, patients carrying these genotypes exhibited significantly better OS (HR = 2.116, P = 0.035) and prolonged PFS (HR = 1.946, P = 0.019) compared to other genotype combinations. Conclusion This study found that GC patients with the GSTP1(AG + GG) genotype demonstrated an enhanced response to oxaliplatin-based chemotherapy and improved survival outcomes, suggesting that GSTP1 genotype status may serve as a valuable predictive biomarker for treatment response. Future pharmacogenomic research should further explore this relationship, potentially enabling more personalized and effective therapeutic strategies in GC treatment.