PloS one, 2012-03, Vol.7 (3), p.e33200-e33200
2012
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- Autor(en) / Beteiligte
- Titel
- Effect of polymorphisms in XPD on clinical outcomes of platinum-based chemotherapy for Chinese non-small cell lung cancer patients
- Ist Teil von
- PloS one, 2012-03, Vol.7 (3), p.e33200-e33200
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- 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. 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. 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. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0033200Titel-ID: cdi_plos_journals_1324393892
- Format
- –
- Schlagworte
- Adenocarcinoma, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols - therapeutic use, Apoptosis, Asian Continental Ancestry Group - genetics, Biology, Cancer, Cancer therapies, Carboplatin - administration & dosage, Carcinoma, Non-Small-Cell Lung - drug therapy, Carcinoma, Non-Small-Cell Lung - ethnology, Carcinoma, Non-Small-Cell Lung - genetics, Care and treatment, Chemotherapy, China, Cisplatin - administration & dosage, Clinical outcomes, Deoxyribonucleic acid, Disease, Disease-Free Survival, DNA, DNA damage, DNA helicase, DNA repair, Drug Administration Schedule, Epidemiology, Experimental design, Female, Gene Frequency, Genetic aspects, Genetic engineering, Genetic polymorphisms, Genetic testing, Genotype, Genotypes, Glutamine, Haplotypes, Humans, Influence, Ionization, Laboratories, Life sciences, Lung cancer, Lung diseases, Lung Neoplasms - drug therapy, Lung Neoplasms - ethnology, Lung Neoplasms - genetics, Male, Mass spectrometry, Mass spectroscopy, Medical prognosis, Medical research, Medicine, Melanoma, Middle Aged, Multiple myeloma, Multivariate Analysis, Non-small cell lung cancer, Non-small cell lung carcinoma, Nucleotide excision repair, Oncology, Patient outcomes, Patients, Platinum, Polymorphism, Single Nucleotide, Prognosis, Rankings, Repair, Respiratory diseases, Skin cancer, Small cell lung cancer, Survival, Treatment Outcome, Xeroderma pigmentosum, Xeroderma Pigmentosum Group D Protein - genetics, XPD protein