Abstract
The influences of glutathione s-transferase P1, M1, and T1 variants on the efficacy of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients were inconsistent in previous studies. Our meta-analysis enrolled 31 publications including 5712 patients and provided more convincing and reliable conclusions. Results showed that GSTP1 IIe105Val IIe/Val and Val/Val Asian patients were more likely to have better response rates compared to IIe/IIe patients (odds ratio (OR) = 1.592, 95% confidence intervals (CIs), 1.087–2.332, P = 0.017). The Asian patients bearing the favorable GSTM1 null genotype were more likely to have better response rates to platinum-based chemotherapy compared to those patients with the unfavorable GSTM1 present genotype (OR = 1.493 (1.192–1.870), P < 0.001). Caucasian lung cancer patients bearing GSTT1 null genotype might be more closely associated with shorter survival time and higher risks of death than the GSTT1 present patients (hazard ratio (HR) = 1.423, CI = 1.084–1.869, P = 0.011). Our meta-analysis suggested that the GSTP1 IIe105Val, GSTM1 and GSTT1 null variants might be predictive factors for the efficacy of platinum-based chemotherapy to NSCLC patients. The use of GSTP1 IIe105Val, GSTM1 and GSTT1 null polymorphisms as predictive factors of efficacy of personalized platinum-based chemotherapy to NSCLC patients requires further verification with multi-center, multi-ethnic and large-sample-size pharmacogenetic studies.
Highlights
Lung cancer is the most common cancer worldwide and the most common causes of cancer death are cancers of the lung and bronchus in both man and woman[1, 2]
29 studies were involved in GSTP1 Ile105Val; 16 studies were involved in GSTM1; and 11 studies were involved in GSTT1
The information of objective response rate (ORR), overall survival (OS) and hazard ratios (HRs), median survival time (MST), the median time to progression (TTP) and the median progression-free survival (PFS) in each study are shown in Tables 2 and 3
Summary
Lung cancer is the most common cancer worldwide and the most common causes of cancer death are cancers of the lung and bronchus in both man and woman[1, 2]. There were two meta-analyses which reported the inconsistent results for evaluating the associations between GSTP1 and GSTM1 polymorphisms and response to platinum-based chemotherapy in lung cancer[17, 40]. These two meta-analyses have not enrolled update studies and just analyzed a few studies, and may have biased conclusions. After combining all available data and derived more precise and comprehensive assessment, we have updated this system review and meta-analysis to find out the reliable associations of GSTP1 (Ile105Val), GSTM1 (null/present) and GSTT1 (null/present) variants with the efficacy and clinical outcomes of NSCLC patients treated with platinum-based chemotherapy
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