Glutathione S-transferases genes variants and chemotherapy efficacy in gastrointestinal cancer patients: a meta-analysis based on 50 pharmacogenetic studies

Background: The role of glutathione s-transferase genes (GSTP1, GSTM1 and GSTT1) variants and the GSTP1 expression level on chemotherapy efficacy of gastrointestinal cancer (GIC) patients were inconsistent. Methods: A meta-analysis about GSTP1, GSTM1 and GSTT1 variants and the GSTP1 expression level on chemotherapy efficacy of GIC patients was performed using data from PubMed, PMC, EMBASE, Web of Science, and Wanfang database. Results: Our meta-analysis enrolled 50 publications including 6518 patients. We found that patients with GIC harboring GSTP1 (IIe105Val) Val locus had higher objective response rates (ORR) than the IIe/IIe genotypic patients (odds ratio (OR) = 1.580, 95% confidence interval (CI) = 1.159-2.154, P = 0.004). Significant associations were found between the Ile105Val variant and overall survival of Caucasian GIC patients (IIe/Val vs. IIe/IIe: OR = 0.797 (0.674-0.944), P = 0.009). Caucasian GIC patients and gastric cancer patients with GSTT1 null genotype had worse response rates compared to GSTT1 present patients (OR = 0.530 (0.356-0.789), P = 0.002; OR = 0.643 (0.463-0.895), P = 0.009, respectively). Conclusion: This meta-analysis illustrates that GSTP1 IIe105Val and GSTT1 null/present variants could be useful predictors of chemotherapy efficacy in patients with gastrointestinal cancer.