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Effect of polymorphisms in XPD on clinical outcomes of platinum-based chemotherapy for Chinese non-small cell lung cancer patients.

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Date
2012-01
Authors
Wu, Wenting
Li, Huan
Wang, Huibo
Zhao, Xueying
Gao, Zhiqiang
Qiao, Rong
Zhang, Wei
Qian, Ji
Wang, Jiucun
Chen, Hongyan
Wei, Qingyi
Han, Baohui
Lu, Daru
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Abstract
PURPOSE: Xeroderma pigmentosum group D (XPD) codes for a DNA helicase involved in nucleotide excision repair that removes platinum-induced DNA damage. Genetic polymorphisms of XPD may affect DNA repair capacity and lead to individual differences in the outcome of patients after chemotherapy. This study aims to identify whether XPD polymorphisms affect clinical efficacy among advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. EXPERIMENTAL DESIGN: 353 stage III-IV NSCLC patients receiving platinum-based chemotherapy as the first-line treatment were enrolled in this study. Four potentially functional XPD polymorphisms (Arg(156)Arg, Asp(312)Asn, Asp(711)Asp and Lys(751)Gln) were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or PCR-based sequencing. RESULTS: Variant genotypes of XPD Asp(312)Asn, Asp(711)Asp and Lys(751)Gln were significantly associated with poorer NSCLC survival (P = 0.006, 0.006, 0.014, respectively, by log-rank test). The most common haplotype GCA (in order of Asp(312)Asn, Asp(711)Asp and Lys(751)Gln) also exhibited significant risk effect on NSCLC survival (log-rank P = 0.001). This effect was more predominant for patients with stage IIIB disease (P = 2.21×10(-4), log-rank test). Increased risks for variant haplotypes of XPD were also observed among patients with performance status of 0-1 and patients with adenocarcinoma. However, no significant associations were found between these polymorphisms, chemotherapy response and PFS. CONCLUSIONS: Our study provides evidence for the predictive role of XPD Asp(312)Asn, Asp(711)Asp and Lys(751)Gln polymorphisms/haplotype on NSCLC prognosis in inoperable advanced NSCLC patients treated with platinum-based chemotherapy.
Type
Journal article
Subject
Humans
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Cisplatin
Carboplatin
Antineoplastic Combined Chemotherapy Protocols
Prognosis
Disease-Free Survival
Treatment Outcome
Drug Administration Schedule
Multivariate Analysis
Gene Frequency
Genotype
Haplotypes
Polymorphism, Single Nucleotide
Adult
Aged
Aged, 80 and over
Middle Aged
Asian Continental Ancestry Group
China
Female
Male
Xeroderma Pigmentosum Group D Protein
Permalink
https://hdl.handle.net/10161/17976
Published Version (Please cite this version)
10.1371/journal.pone.0033200
Publication Info
Wu, Wenting; Li, Huan; Wang, Huibo; Zhao, Xueying; Gao, Zhiqiang; Qiao, Rong; ... Lu, Daru (2012). Effect of polymorphisms in XPD on clinical outcomes of platinum-based chemotherapy for Chinese non-small cell lung cancer patients. PloS one, 7(3). pp. e33200. 10.1371/journal.pone.0033200. Retrieved from https://hdl.handle.net/10161/17976.
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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