Dataset Information

Polymorphisms of CCNB1 Associated With the Clinical Outcomes of Platinum-Based Chemotherapy in Chinese NSCLC Patients.

ABSTRACT: As a crucial cell cycle regulator and G2/M phase promotor, CCNB1 played an essential role in progression of chemotherapy related cell death. Platinum-based chemotherapy is still the first-line chemotherapy regimen for most advanced NSCLC patients. We aim to investigate the correlation of CCNB1 polymorphisms to the efficiency of platinum-based chemotherapy in Chinese advanced NSCLC patients. We enrolled 972 patients with advanced NSCLC, and extracted DNA from their peripheral blood for genotyping CCNB1 four tagSNPs which selected from the Hapmap database. We analyzed the association of CCNB1 four tagSNPs with efficiency of platinum-based chemotherapy. We found that rs2069429 and rs2069433 of CCNB1 were associated with the OS of advanced NSCLC patients. Patients with GG genotype of rs2069429 had longer OS than non-GG patients (HR=0.81, 95%CI=0.68-0.95, p=0.009); and patients with AA genotype of rs2069433 had longer OS than non-AA patients (HR=0.78, 95%CI=0.61-0.98, p=0.036). And the haplotype GAAA of CCNB1 was a putative factor in subgroup patients with clinical stage IV. The association of CCNB1 polymorphisms and toxicities after platinum-based chemotherapy was assessed. Rs2069433 and rs350104 were related with gastrointestinal toxicity of platinum-based chemotherapy. The patients with GG genotype of rs2069433 (p=0.013) and/or non-GG genotype of rs350104 (p=0.042) may have a severe gastrointestinal toxicity after chemotherapy, and then clinician may can reduce the dosage of chemotherapy agents to avoid sever toxicities in these patients. In summary, CCNB1 polymorphisms may contribute to the clinical efficiency of platinum-based chemotherapy in advanced NSCLC patients, and it is helpful for the personalized treatment.

SUBMITTER: Liu D

PROVIDER: S-EPMC5688932 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Polymorphisms of CCNB1 Associated With the Clinical Outcomes of Platinum-Based Chemotherapy in Chinese NSCLC Patients.

Liu Di D Xu Wen W Ding Xi X Yang Yang Y Su Bo B Fei Ke K

Journal of Cancer 20171017 18

As a crucial cell cycle regulator and G2/M phase promotor, CCNB1 played an essential role in progression of chemotherapy related cell death. Platinum-based chemotherapy is still the first-line chemotherapy regimen for most advanced NSCLC patients. We aim to investigate the correlation of CCNB1 polymorphisms to the efficiency of platinum-based chemotherapy in Chinese advanced NSCLC patients. We enrolled 972 patients with advanced NSCLC, and extracted DNA from their peripheral blood ...[more]

PMID: 29151966

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Project description:BackgroundBase excision repair (BER) pathway is a DNA repair pathway that is important in carcinogenesis and in response to DNA-damaging chemotherapy. XRCC1 is one of important molecular markers for BER. So far, the role of XRCC1 polymorphisms with clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy is inconclusive. To explore the relationship between XRCC1 polymorphisms and platinum-based chemotherapy in advanced NSCLC patients, we performed this meta-analysis.MethodsCrude odds ratios (ORs), Cox proportional hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were adopted to assess the strength of association between XRCC1 polymorphisms and response rate, Overall survival (OS) and progression free survival (PFS) of advanced NSCLC treated with platinum-based chemotherapy. Q test and I 2 test were used for the assessment of heterogeneity. Subgroup analyses were conducted when heterogeneity exists. Begg's funnel plots and Egger's linear regression test were used to estimate publication bias. Sensitivity analysis was performed to evaluate the stability of the result.ResultsA total of 19 studies including 2815 individuals were eligible for the analysis, results showed XRCC1 194Arg allele was negatively associated with the objective response rate relative to 194Trp, and results of homozygous model, dominant model and heterozygous model suggested a gene dosage effect negative correlation between 194Arg allele and objective response rate(ArgArg vs TrpTrp: OR = 0.64(95%CI: 0.44-0.91); ArgArg + TrpArg vs TrpTrp: OR = 0.79(95%CI: 0.57-1.11); TrpArg vs TrpTrp: OR = 1.05(95%CI: 0.73-1.51)). XRCC1 399Gln may indicate favorable overall survival (GlnGln + GlnArg vs ArgArg: HR = 0.65(95%CI: 0.43-0.98)) and favorable PFS (GlnGln vs ArgArg: HR = 0.72(95%CI: 0.48-0.97)) in Asian patients; while in Caucasian patients, XRCC1 399Gln indicated poorer overall survival (GlnGln vs ArgArg: HR = 2.29(95%CI: 1.25-3.33)).ConclusionsOur results indicated that in NSCLC patients treated with platinum-based regimen, XRCC1 194Arg allele suggest poor objective response rate, the GlnGln genotype of XRCC1 399 suggest poorer overall survival in Caucasian patients, and longer PFS in Asian patients.

Dataset Information

Polymorphisms of CCNB1 Associated With the Clinical Outcomes of Platinum-Based Chemotherapy in Chinese NSCLC Patients.

Publications

Polymorphisms of <i>CCNB1</i> Associated With the Clinical Outcomes of Platinum-Based Chemotherapy in Chinese NSCLC Patients.

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