Polymorphisms of homologous recombination genes and clinical outcomes of non-small cell lung cancer patients treated with definitive radiotherapy.

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Yin, Ming

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Liao, Zhongxing

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Huang, Yu-Jing

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Liu, Zhensheng

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Yuan, Xianglin

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Gomez, Daniel

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Wang, Li-E

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Wei, Qingyi

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Bernhard, Eric J

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2019-02-01T15:25:12Z

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2019-02-01T15:25:12Z

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2011-01

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2019-02-01T15:25:10Z

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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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PONE-D-11-01801

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1932-6203

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1932-6203

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https://hdl.handle.net/10161/18015

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eng

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Public Library of Science (PLoS)

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PloS one

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10.1371/journal.pone.0020055

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Humans

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Carcinoma, Non-Small-Cell Lung

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Lung Neoplasms

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Radiation Pneumonitis

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DNA-Binding Proteins

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Treatment Outcome

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Survival Analysis

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Retrospective Studies

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Recombination, Genetic

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Polymorphism, Single Nucleotide

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Middle Aged

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Female

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Male

dc.title

Polymorphisms of homologous recombination genes and clinical outcomes of non-small cell lung cancer patients treated with definitive radiotherapy.

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Journal article

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Wei, Qingyi|0000-0002-3845-9445|0000-0003-4115-4439

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e20055

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5

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Staff

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Duke

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School of Medicine

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Duke Cancer Institute

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Institutes and Centers

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Population Health Sciences

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Basic Science Departments

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Medicine, Medical Oncology

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Medicine

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Clinical Science Departments

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Published

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6

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