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Genetic variants of DNA repair genes predict the survival of patients with esophageal squamous cell cancer receiving platinum-based adjuvant chemotherapy.

dc.contributor.author Wei, Qingyi
dc.contributor.author Zhou, Fei
dc.contributor.author Zhu, Meiling
dc.contributor.author Wang, Mengyun
dc.contributor.author Qiu, Lixin
dc.contributor.author Cheng, Lei
dc.contributor.author Jia, Ming
dc.contributor.author Xiang, Jiaqing
dc.date.accessioned 2019-02-01T15:23:46Z
dc.date.available 2019-02-01T15:23:46Z
dc.date.issued 2016-05-31
dc.identifier 10.1186/s12967-016-0903-z
dc.identifier.issn 1479-5876
dc.identifier.issn 1479-5876
dc.identifier.uri https://hdl.handle.net/10161/18009
dc.description.abstract Adjuvant chemotherapy in patients with resected esophageal squamous cell cancer (ESCC) remains controversial for its uncertain role in improving overall survival (OS). Nucleotide excision repair (NER) removes DNA-adducts in tumor cells induced by the platinum-based chemotherapy and thus may modulate efficacy of the treatment. The present study evaluated if single nucleotide polymorphisms (SNPs) of NER genes were prognostic biomarkers in ESCC patients treated with platinum-based adjuvant chemotherapy (PAC).The analysis included 572 patients, for whom six SNPs of NER genes [i.e., XPC (rs1870134 and rs2228001), ERCC2/XPD rs238406 and ERCC5/XPG (rs2094258, rs2296147 and rs873601)] were detected with the TaqMan assay. Kaplan-Meier analyses and Cox proportional hazards models were used to evaluate their associations with disease free survival (DFS) and OS of these ESCC patients receiving PAC. Receiving operating characteristic curve analysis was used to evaluate the role of the risk genotypes in the DFS and OS.We found that ERCC5/XPG rs2094258 and rs873601 and ERCC2/XPD rs238406 SNPs were independently associated with poorer DFS and OS of ESCC patients [ERCC5/XPG rs2094258: CT+TT vs. CC: adjusted hazards ratio (adjHR) = 1.68 and P = 0.012 for DFS; adjHR = 1.99 and P = 0.0001 for OS; ERCC5/XPG rs873601: GA+GG vs. AA: adjHR = 1.59 and P = 0.024 for DFS; adjHR = 1.91 and P = 0.0005 for OS; ERCC2/XPD rs238406: TT vs. GG+GT: adjHR = 1.43 and P = 0.020 for DFS; adjHR = 1.52 and P = 0.008 for OS]. These HRs increased as the number of risk genotypes increased in the combined analysis. The model combining the risk genotypes with clinical characteristics or the TNM stage system was better in predicting outcomes in ESCC patients with PAC.SNPs of ERCC2/XPD and ERCC5/XPG may independently and jointly predict survival of ESCC patients treated with PAC in this study population. Further validation in other study populations is warranted.
dc.language eng
dc.publisher Springer Nature
dc.relation.ispartof Journal of translational medicine
dc.relation.isversionof 10.1186/s12967-016-0903-z
dc.subject Humans
dc.subject Carcinoma, Squamous Cell
dc.subject Esophageal Neoplasms
dc.subject Platinum
dc.subject Prognosis
dc.subject Disease-Free Survival
dc.subject Chemotherapy, Adjuvant
dc.subject Multivariate Analysis
dc.subject ROC Curve
dc.subject Demography
dc.subject DNA Repair
dc.subject Polymorphism, Single Nucleotide
dc.subject Asian Continental Ancestry Group
dc.subject Genetic Association Studies
dc.subject Kaplan-Meier Estimate
dc.title Genetic variants of DNA repair genes predict the survival of patients with esophageal squamous cell cancer receiving platinum-based adjuvant chemotherapy.
dc.type Journal article
dc.date.updated 2019-02-01T15:23:43Z
pubs.begin-page 154
pubs.issue 1
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Population Health Sciences
pubs.organisational-group Basic Science Departments
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group Medicine
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 14
duke.contributor.orcid Wei, Qingyi|0000-0002-3845-9445


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