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Effect of GSTP1 and ABCC2 Polymorphisms on Treatment Response in Patients with Advanced Non-Small Cell Lung Cancer Undergoing Platinum-Based Chemotherapy: A Study in a Chinese Uygur Population.

ABSTRACT: BACKGROUND Gene polymorphisms are associated with sensitivity to platinum drugs. This study aimed to investigate the polymorphisms of GSTP1 rs1695 locus and ABCC2 rs717620 locus, and the sensitivity of patients with advanced non-small cell lung cancer (NSCLC) to platinum drugs in a Xinjiang Uygur population. MATERIAL AND METHODS The gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 of Uygur NSCLC patients were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between the prognosis of advanced NSCLC Uygur patients and the gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 was analyzed using progression-free survival (PFS) and overall survival (OS) as the major outcome indicators. RESULTS The median PFS of patients with advanced NSCLC was 6.9 months and the OS of Uygur patients with advanced NSCLC was 10.8 months. Kaplan-Meier survival analysis indicated that survival time of patients with GSTP1 AG + GG was significantly longer than in patients with AA gene (P<0.05), and survival time of patients with ABCC2 CT + TT was significantly longer than in patients with the CC gene (P<0.05). CONCLUSIONS Polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 can be used to predict the outcomes of Uygur patients with advanced NSCLC who have received platinum-based chemotherapy. Additionally, this information could be used to guide the individualized treatment of Uygur patients with advanced NSCLC.

SUBMITTER: Han ZG

PROVIDER: S-EPMC5414593 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Effect of GSTP1 and ABCC2 Polymorphisms on Treatment Response in Patients with Advanced Non-Small Cell Lung Cancer Undergoing Platinum-Based Chemotherapy: A Study in a Chinese Uygur Population.

Han Zhi-Gang ZG Tao Jie J Yu Ting-Ting TT Shan Li L

Medical science monitor : international medical journal of experimental and clinical research 20170426

BACKGROUND Gene polymorphisms are associated with sensitivity to platinum drugs. This study aimed to investigate the polymorphisms of GSTP1 rs1695 locus and ABCC2 rs717620 locus, and the sensitivity of patients with advanced non-small cell lung cancer (NSCLC) to platinum drugs in a Xinjiang Uygur population. MATERIAL AND METHODS The gene polymorphisms of GSTP1 rs1695 and ABCC2 rs717620 of Uygur NSCLC patients were assessed by polymerase chain reaction-restriction fragment length polymorphism (PC ...[more]

PMID: 28442702

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Project description:Background and objectiveOverexpression of COX-2 is proved to contribute to tumor promotion and carcinogenesis through stimulating cell proliferation, inhibiting apoptosis and enhancing the invasiveness of cancer cells. Apoptosis-related molecules are potential predictive markers for survival and toxicity in platinum treatment. This study aimed at investigating the association between COX-2 polymorphisms and the occurrence of grade 3 or 4 toxicity in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.Materials and methodsTwo hundred and twelve patients with inoperable stage IIIB-IV NSCLC received first-line chemotherapy between 2007 and 2009 were recruited in this study. Four functional COX-2 polymorphisms were genotyped by PCR-based restriction fragment length polymorphism (RFLP) methods.ResultsThe incidence of grade 3 or 4 hematologic toxicity was significantly higher in G allele carriers of the COX-2 rs689466 (-1195G/A) polymorphism compared with wild-type homozygotes AA (P value = 0.008; odds ratio, 2.47; 95% confidence internal, 1.26-4.84) and the significance still existed after the Bonferroni correction. Statistically significant difference was also found in grade 3 or 4 leukopenia (P value = 0.010; OR = 2.82; 95%CI = 1.28-6.20). No other significant association was observed between genotype and toxicity in the study. The haplotype analysis showed that the haplotype AGG was associated with a reduced risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 0.59; 95%CI = 0.39-0.88 and P value = 0.025; OR = 0.61; 95%CI = 0.39-0.94, respectively) while the haplotype GGG was associated with an increased risk of grade 3 or 4 hematologic and leukopenia toxicity (P value = 0.009; OR = 1.71; 95%CI = 1.14-2.56 and P value = 0.025; OR = 1.65; 95%CI = 1.06-2.57, respectively).ConclusionThis investigation for the first time suggested that polymorphism in COX-2 rs689466 may be a potent bio-marker in predicting severe hematologic toxicity in NSCLC patients after platinum-based chemotherapy.

Dataset Information

Effect of GSTP1 and ABCC2 Polymorphisms on Treatment Response in Patients with Advanced Non-Small Cell Lung Cancer Undergoing Platinum-Based Chemotherapy: A Study in a Chinese Uygur Population.

Publications

Effect of GSTP1 and ABCC2 Polymorphisms on Treatment Response in Patients with Advanced Non-Small Cell Lung Cancer Undergoing Platinum-Based Chemotherapy: A Study in a Chinese Uygur Population.

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