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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.

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    Date
    2016-05-31
    Authors
    Wei, Qingyi
    Zhou, Fei
    Zhu, Meiling
    Wang, Mengyun
    Qiu, Lixin
    Cheng, Lei
    Jia, Ming
    Xiang, Jiaqing
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    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.
    Type
    Journal article
    Subject
    Humans
    Carcinoma, Squamous Cell
    Esophageal Neoplasms
    Platinum
    Prognosis
    Disease-Free Survival
    Chemotherapy, Adjuvant
    Multivariate Analysis
    ROC Curve
    Demography
    DNA Repair
    Polymorphism, Single Nucleotide
    Asian Continental Ancestry Group
    Genetic Association Studies
    Kaplan-Meier Estimate
    Permalink
    https://hdl.handle.net/10161/18009
    Published Version (Please cite this version)
    10.1186/s12967-016-0903-z
    Publication Info
    Wei, Qingyi; Zhou, Fei; Zhu, Meiling; Wang, Mengyun; Qiu, Lixin; Cheng, Lei; ... Xiang, Jiaqing (2016). Genetic variants of DNA repair genes predict the survival of patients with esophageal squamous cell cancer receiving platinum-based adjuvant chemotherapy. Journal of translational medicine, 14(1). pp. 154. 10.1186/s12967-016-0903-z. Retrieved from https://hdl.handle.net/10161/18009.
    This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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    Scholars@Duke

    Wei

    Qingyi Wei

    Professor in Population Health Sciences
    Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally recognized epidemiologist focused on the molecular and genetic epidemiology of head and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and genetic determinants for the DNA repair deficient phenotype and
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