Role of GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms in the response to chemotherapy and overall survival of advanced non-small cell lung cancer

Abstract

ABSTRACT. We evaluated the association between GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms and treatment outcomes of advanced non-small cell lung carcinoma. Between January 2010 and December 2012, a total of 244 patients with non-small cell lung carcinoma were recruited from Yiwu Central Hospital. The GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism and the results were statistically analyzed. Conditional regression analysis, showed that individuals carrying the null GSTM1 were associated with an increased risk of response to chemotherapy when 2 W. Jia et al. Genetics and Molecular Research 15 (3): gmr.15037668 compared to the present GSTM1 (odds ratio = 1.88, 95% confidence interval (CI) = 1.01-3.47). Moreover, the GG genotype of GSTP1 IIe105Val was associated with a better response to chemotherapy compared to the AA genotype (odds ratio = 2.77, 95%CI = 1.14-6.64). The null GSTM1 genotype was associated with a lower risk of death from all causes when compared with the present GSTM1 genotype (hazard ratio = 2.16, 95%CI = 1.10-4.38). Moreover, the GG genotype of GSTP1 IIe105Val was correlated with a reduced risk of death from all causes compared with the AA genotype (hazard ratio = 2.94, 95%CI = 1.11-8.68). In conclusion, we found that the null GSTM1 and the GG genotype of GSTP1 IIe105Val were correlated with a good response to chemotherapy and improved overall survival of advanced non-small cell lung carcinoma patients.

Glutathione S-Transferase Gene Polymorphisms are Associated with an Improved Treatment Response to Cisplatin-Based Chemotherapy in Patients with Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis

“…After carefully screening the titles and abstracts, 121 studies were excluded. Finally, 23 studies met the study selection criteria for meta-analysis [ 2 , 3 , 7 – 16 , 19 – 21 , 23 – 30 ] ( Figure 1 ). Among the 23 studies, there were eight studies of non-small cell lung cancer (NSCLC) with 640 cases and 928 controls for the GSTM1 null genotype, six studies with 518 cases and 822 controls for the GSTT1 null genotype, 23 studies including 1733 cases and 1374 controls for the GSTP1 IIe105Val genotype.…”

“…These studies contained two subgroups with 20 studies including patients from East-Asia and three studies that included Caucasian patients with NSCLC. The essential information of the included 23 publications are shown in Tables 1 – 5 [ 2 , 3 , 7 – 16 , 19 – 21 , 23 – 30 ]. Three individuals reviewed the studies to avoid potential bias in data interpretation.…”

“…The Newcastle-Ottawa Scale (NOS) was used to evaluated the quality of these included studies, based on a scoring system with three components: the selection of the subjects (0–4 points); the comparability of the study groups (0–2 points); the determination of the outcome of interest (treatment response) (0–3 points). The highest NOS score for each publication was 9 points, and in this meta-analysis, two studies had a NOS score of 9 [ 11 , 31 ]; 11 studies had a NOS score of 8 [ 8 – 10 , 12 , 13 , 15 , 16 , 20 , 25 , 26 , 30 ]; eight studies had a NOS score of 7 [ 2 , 7 , 14 , 19 , 21 , 24 , 28 , 29 ]; and two studies had a NOS score of 6 [ 23 , 27 ].…”

Deletion of GSTM1 and GSTT1 Genes and Lung Cancer Survival: a Systematic Review

“…The reviewed studies show that GSTM1 deletion appears to have no effect or could imply a slightly shorter survival. Three studies showed better survival for null GSTM1 (12,13,27) but only 2 of them had statistically significant results (12,13). Regarding GSTT1 deletion, most of the studies found no effect or a tendency to present a worse survival for individuals with the gene absent.…”

“…II). Some studies showed positive results in overall survival related to GSTM1 deletion (12,13,27), and 2 of them (12, 13) showed significant results through improving the response to chemotherapy. Median survival was 2.82 months longer for GSTM1-null patients (13).…”