Effect of polymorphisms in XPD on clinical outcomes of platinum-based chemotherapy for Chinese non-small cell lung cancer patients.
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 articleSubject
HumansCarcinoma, 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
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https://hdl.handle.net/10161/17976Published Version (Please cite this version)
10.1371/journal.pone.0033200Publication 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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Show full item recordScholars@Duke
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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