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

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Wu, Wenting

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Li, Huan

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Wang, Huibo

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Zhao, Xueying

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Gao, Zhiqiang

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Qiao, Rong

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Zhang, Wei

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Qian, Ji

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Wang, Jiucun

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Chen, Hongyan

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Wei, Qingyi

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Han, Baohui

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Lu, Daru

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2019-02-01T15:09:37Z

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2019-02-01T15:09:37Z

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2012-01

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2019-02-01T15:09:36Z

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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.

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PONE-D-11-22211

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1932-6203

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1932-6203

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https://hdl.handle.net/10161/17976

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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.0033200

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Humans

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Carcinoma, Non-Small-Cell Lung

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Lung Neoplasms

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Cisplatin

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Carboplatin

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Antineoplastic Combined Chemotherapy Protocols

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Prognosis

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Disease-Free Survival

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Treatment Outcome

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Drug Administration Schedule

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Multivariate Analysis

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Gene Frequency

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Genotype

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Haplotypes

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Polymorphism, Single Nucleotide

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Adult

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Aged

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Aged, 80 and over

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Middle Aged

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Asian Continental Ancestry Group

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China

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Female

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Male

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Xeroderma Pigmentosum Group D Protein

dc.title

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

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Journal article

duke.contributor.orcid

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

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e33200

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3

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School of Medicine

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Duke

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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

pubs.publication-status

Published

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7

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