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Polymorphisms of Homologous Recombination Genes and Clinical Outcomes of Non-Small Cell Lung Cancer Patients Treated with Definitive Radiotherapy

The repair of DNA double-strand breaks (DSBs) is the major mechanism to maintain genomic stability in response to irradiation. We hypothesized that genetic polymorphisms in DSB repair genes may affect clinical outcomes among non-small cell lung cancer (NSCLC) patients treated with definitive radio(c...

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Autores principales: Yin, Ming, Liao, Zhongxing, Huang, Yu-Jing, Liu, Zhensheng, Yuan, Xianglin, Gomez, Daniel, Wang, Li-E, Wei, Qingyi
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102071/
https://www.ncbi.nlm.nih.gov/pubmed/21647442
http://dx.doi.org/10.1371/journal.pone.0020055
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author Yin, Ming
Liao, Zhongxing
Huang, Yu-Jing
Liu, Zhensheng
Yuan, Xianglin
Gomez, Daniel
Wang, Li-E
Wei, Qingyi
author_facet Yin, Ming
Liao, Zhongxing
Huang, Yu-Jing
Liu, Zhensheng
Yuan, Xianglin
Gomez, Daniel
Wang, Li-E
Wei, Qingyi
author_sort Yin, Ming
collection PubMed
description The repair of DNA double-strand breaks (DSBs) is the major mechanism to maintain genomic stability in response to irradiation. We hypothesized that genetic polymorphisms in DSB repair genes may affect clinical outcomes among non-small cell lung cancer (NSCLC) patients treated with definitive radio(chemo)therapy. We genotyped six potentially functional single nucleotide polymorphisms (SNPs) (i.e., RAD51 −135G>C/rs1801320 and −172G>T/rs1801321, XRCC2 4234G>C/rs3218384 and R188H/rs3218536 G>A, XRCC3 T241M/rs861539 and NBN E185Q/rs1805794) and estimated their associations with overall survival (OS) and radiation pneumonitis (RP) in 228 NSCLC patients. We found a predictive role of RAD51 −135G>C SNP in RP development (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.31–0.86, P = 0.010 for CG/CC vs. GG). We also found that RAD51 −135G>C and XRCC2 R188H SNPs were independent prognostic factors for overall survival (adjusted HR = 1.70, 95% CI, 1.14–2.62, P = 0.009 for CG/CC vs. GG; and adjusted HR = 1.70; 95% CI, 1.02–2.85, P = 0.043 for AG vs. GG, respectively) and that the SNP-survival association was most pronounced in the presence of RP. Our study suggests that HR genetic polymorphisms, particularly RAD51 −135G>C, may influence overall survival and radiation pneumonitis in NSCLC patients treated with definitive radio(chemo)therapy. Large studies are needed to confirm our findings.
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spelling pubmed-31020712011-06-06 Polymorphisms of Homologous Recombination Genes and Clinical Outcomes of Non-Small Cell Lung Cancer Patients Treated with Definitive Radiotherapy Yin, Ming Liao, Zhongxing Huang, Yu-Jing Liu, Zhensheng Yuan, Xianglin Gomez, Daniel Wang, Li-E Wei, Qingyi PLoS One Research Article The repair of DNA double-strand breaks (DSBs) is the major mechanism to maintain genomic stability in response to irradiation. We hypothesized that genetic polymorphisms in DSB repair genes may affect clinical outcomes among non-small cell lung cancer (NSCLC) patients treated with definitive radio(chemo)therapy. We genotyped six potentially functional single nucleotide polymorphisms (SNPs) (i.e., RAD51 −135G>C/rs1801320 and −172G>T/rs1801321, XRCC2 4234G>C/rs3218384 and R188H/rs3218536 G>A, XRCC3 T241M/rs861539 and NBN E185Q/rs1805794) and estimated their associations with overall survival (OS) and radiation pneumonitis (RP) in 228 NSCLC patients. We found a predictive role of RAD51 −135G>C SNP in RP development (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.31–0.86, P = 0.010 for CG/CC vs. GG). We also found that RAD51 −135G>C and XRCC2 R188H SNPs were independent prognostic factors for overall survival (adjusted HR = 1.70, 95% CI, 1.14–2.62, P = 0.009 for CG/CC vs. GG; and adjusted HR = 1.70; 95% CI, 1.02–2.85, P = 0.043 for AG vs. GG, respectively) and that the SNP-survival association was most pronounced in the presence of RP. Our study suggests that HR genetic polymorphisms, particularly RAD51 −135G>C, may influence overall survival and radiation pneumonitis in NSCLC patients treated with definitive radio(chemo)therapy. Large studies are needed to confirm our findings. Public Library of Science 2011-05-25 /pmc/articles/PMC3102071/ /pubmed/21647442 http://dx.doi.org/10.1371/journal.pone.0020055 Text en Yin et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yin, Ming
Liao, Zhongxing
Huang, Yu-Jing
Liu, Zhensheng
Yuan, Xianglin
Gomez, Daniel
Wang, Li-E
Wei, Qingyi
Polymorphisms of Homologous Recombination Genes and Clinical Outcomes of Non-Small Cell Lung Cancer Patients Treated with Definitive Radiotherapy
title Polymorphisms of Homologous Recombination Genes and Clinical Outcomes of Non-Small Cell Lung Cancer Patients Treated with Definitive Radiotherapy
title_full Polymorphisms of Homologous Recombination Genes and Clinical Outcomes of Non-Small Cell Lung Cancer Patients Treated with Definitive Radiotherapy
title_fullStr Polymorphisms of Homologous Recombination Genes and Clinical Outcomes of Non-Small Cell Lung Cancer Patients Treated with Definitive Radiotherapy
title_full_unstemmed Polymorphisms of Homologous Recombination Genes and Clinical Outcomes of Non-Small Cell Lung Cancer Patients Treated with Definitive Radiotherapy
title_short Polymorphisms of Homologous Recombination Genes and Clinical Outcomes of Non-Small Cell Lung Cancer Patients Treated with Definitive Radiotherapy
title_sort polymorphisms of homologous recombination genes and clinical outcomes of non-small cell lung cancer patients treated with definitive radiotherapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102071/
https://www.ncbi.nlm.nih.gov/pubmed/21647442
http://dx.doi.org/10.1371/journal.pone.0020055
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