GSTP1 A313G, GSTM1 , and GSTT1 gene polymorphisms influence clinical outcome in advanced non-small cell lung cancer patients receiving first-line platinum-based chemotherapy: an updated meta-analysis with trial sequential analysis

// Qiang Xiao 1 , Quan Zhou 2 , Mu Mei 1 , Wenjun Pei 1 , Yeqiang Zou 1 , Erdong Chen 1 , Susu Dong 1 , Yafen Tan 1 , Tianli Wang 1 and Wei Du 3 1 Department of Respiratory Medicine, The First People’s Hospital of Changde City, Hunan Province, P.R. China 2 Department of Science and Education, The First People’s Hospital of Changde City, Hunan Province, P.R. China 3 Department of Pathology, The First People’s Hospital of Changde City, Hunan Province, P.R. China Correspondence to: Tianli Wang, email: wtl195@163.com Wei Du, email: dw417@sina.com Keywords: GSTP1; GSTM1; GSTT1; advanced non-small cell lung cancer; chemotherapy Received: April 07, 2017      Accepted: December 27, 2017      Published: January 02, 2018 ABSTRACT The GSTP1 A313G, GSTM1 and GSTT1 gene polymorphisms reportedly correlate with prognosis in advanced non-small cell lung cancer (NSCLC) patients receiving first-line platinum-based chemotherapy, but the results are inconsistent. An updated meta-analysis and trial sequential analysis (TSA) were performed to further examine the correlation and determine whether currently available evidence is sufficient and conclusive. A total of 25 studies covering 4410 advanced NSCLC patients were included. For the GSTP1 A313G polymorphism, the G allele was associated with a better treatment response under four genetic models and better overall survival (OS) under the homozygote model (HR = 0.550, 95% CI = 0.337–0.898, P = 0.017). The GSTM1 null genotype was also correlated with a better response (OR = 1.654, 95%CI = 1.290–2.120, P = 0.000) but not better OS. However, the GSTT1 gene variant had no significant effect on clinical outcome. The TSA results indicated that the evidence of the effect was sufficient for GSTP1 A313G under three genetic models (dominant, heterozygote, and allele), for GSTM1 , and for GSTT1 , but the correlations were not confirmed for the homozygote and recessive models of GSTP1 A313G . Our study suggest the GSTP1 313G and GSTM1 null genotypes correlate with a better clinical outcome for advanced NSCLC patients receiving platinum-based chemotherapy.