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Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement

BACKGROUND: Base 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...

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Autores principales: Li, Dan-Juan, Xiao, Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526237/
https://www.ncbi.nlm.nih.gov/pubmed/28743242
http://dx.doi.org/10.1186/s12885-017-3487-y
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author Li, Dan-Juan
Xiao, Dong
author_facet Li, Dan-Juan
Xiao, Dong
author_sort Li, Dan-Juan
collection PubMed
description BACKGROUND: Base 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. METHODS: Crude 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. RESULTS: A 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)). CONCLUSIONS: Our 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-017-3487-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-55262372017-08-02 Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement Li, Dan-Juan Xiao, Dong BMC Cancer Research Article BACKGROUND: Base 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. METHODS: Crude 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. RESULTS: A 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)). CONCLUSIONS: Our 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-017-3487-y) contains supplementary material, which is available to authorized users. BioMed Central 2017-07-25 /pmc/articles/PMC5526237/ /pubmed/28743242 http://dx.doi.org/10.1186/s12885-017-3487-y Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Li, Dan-Juan
Xiao, Dong
Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement
title Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement
title_full Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement
title_fullStr Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement
title_full_unstemmed Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement
title_short Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement
title_sort association between the xrcc1 polymorphisms and clinical outcomes of advanced nsclc treated with platinum-based chemotherapy: a meta-analysis based on the prisma statement
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526237/
https://www.ncbi.nlm.nih.gov/pubmed/28743242
http://dx.doi.org/10.1186/s12885-017-3487-y
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