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Association between common polymorphisms in ERCC gene and prognosis of osteosarcoma in patients treated with chemotherapy: a meta-analysis.

ABSTRACT: Purpose:Some previous studies have sought to investigate the roles of excision repair cross complementation group 1 (ERCC1), ERCC2, ERCC4, and ERCC5 gene polymorphisms in the prognosis of osteosarcoma patients. However, their results were inconclusive. Here, we performed a meta-analysis to determine the strength of the association between eight polymorphisms in the ERCC genes (rs11615, rs3212986, rs2298881, rs13181, rs1799793, rs1800067, rs2296147, and rs1047768) and prognosis of osteosarcoma patients treated with chemotherapy. Materials and methods:We retrieved the relevant studies from PubMed, Embase, and Web of Science in human osteosarcoma published prior to July 2017. Primary outcomes included overall survival (OS) and event-free survival, expressed by hazard ratios (HRs) with their corresponding 95% CIs. STATA software (version 12.0) was utilized to perform data synthesis. Results:A total of 13 eligible follow-up studies involving 2,303 patients met all the inclusion criteria, conducted in two populations of ethnic descent: 11 Asians and two Caucasians. In the present meta-analysis, we demonstrated that the homozygous variant genotypes in ERCC2 rs1799793 and ERCC5 rs2296147 were significantly associated with OS in osteosarcoma (TT vs GG for rs1799793: HR = 0.62, 95% CI = 0.41-0.93, Pheterogeneity = 0.310, I2 = 15.3%, P = 0.020; TT vs CC for rs2296147: HR = 0.42, 95% CI = 0.23-0.78, Pheterogeneity = 0.708, I2 = 0.0%, P = 0.006). In addition, no evidence of association was observed between prognosis in osteosarcoma and ERCC1 rs11615, ERCC1 rs3212986, ERCC1 rs2298881, ERCC2 rs13181, ERCC4 rs1800067, and ERCC5 rs1047768 polymorphisms. Conclusion:Our meta-analysis indicated that TT genotype in the ERCC2 rs1799793 and ERCC5 rs2296147 might prolong the survival time of patients with osteosarcoma, suggesting that the rs1799793 and rs2296147 polymorphisms can be used as predictors for prognosis of osteosarcoma patients treated with chemotherapy.

SUBMITTER: Li C

PROVIDER: S-EPMC6011878 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Association between common polymorphisms in ERCC gene and prognosis of osteosarcoma in patients treated with chemotherapy: a meta-analysis.

Li Chunpu C Yu Xin X Guo Dongmei D Liu Guanhua G Zhang Kaigang K Teng Qingliang Q Lin Hai H

OncoTargets and therapy 20180618

<h4>Purpose</h4>Some previous studies have sought to investigate the roles of excision repair cross complementation group 1 (ERCC1), ERCC2, ERCC4, and ERCC5 gene polymorphisms in the prognosis of osteosarcoma patients. However, their results were inconclusive. Here, we performed a meta-analysis to determine the strength of the association between eight polymorphisms in the ERCC genes (rs11615, rs3212986, rs2298881, rs13181, rs1799793, rs1800067, rs2296147, and ...[more]

PMID: 29950854

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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.

Project description:BackgroundLung cancer is still the most lethal malignancy in the world, according to the report of Cancer Statistics in 2021. Platinum-based chemotherapy combined with immunotherapy is the first-line treatment in lung cancer patients. However, the 5-year survival rate is always affected by the adverse reactions and drug resistance caused by platinum-based chemotherapy. DNA damage and repair system is one of the important mechanisms that can affect the response to chemotherapy and clinical outcomes in lung cancer patients.ObjectiveThe objective of this study is to find the relationship between the polymorphisms of DNA repair genes with the prognosis of platinum-based chemotherapy in lung cancer patients.Patients and methodsWe performed genotyping in 17 single nucleotide polymorphisms (SNPs) of Excision Repair Cross-Complementation group (ERCC) genes and X-ray Repair Cross-Complementing (XRCC) genes of 345 lung cancer patients via Sequenom MassARRAY. We used Cox proportional hazard models, state, and plink to analyze the associations between SNPs and the prognosis of lung cancer patients.ResultsWe found that the ERCC5 rs873601 was associated with the overall survival time in lung cancer patients treated with platinum-based chemotherapy (p = 0.031). There were some polymorphisms that were related to the prognosis in specific subgroups of lung cancer. Rs873601 showed a great influence on the prognosis of patients more than 55 years, Small Cell Lung Cancer (SCLC), and smoking patients. Rs2444933 was associated with prognosis in age less than 55 years, SCLC, metastasis, and stage III/IV/ED patients. Rs3740051 played an important role in the prognosis of SCLC and metastasis patients. Rs1869641 was involved in the prognosis of SCLC patients. Rs1051685 was related to the prognosis in non-metastasis patients.ConclusionThe ERCC5 rs873601 (G>A) was a valuable biomarker for predicting the prognosis in lung cancer patients treated with platinum-based chemotherapy.

Dataset Information

Association between common polymorphisms in ERCC gene and prognosis of osteosarcoma in patients treated with chemotherapy: a meta-analysis.

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Association between common polymorphisms in <i>ERCC</i> gene and prognosis of osteosarcoma in patients treated with chemotherapy: a meta-analysis.

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