Genetic polymorphism of XRCC1 Arg399Gln is associated with survival in non-small-cell lung cancer patients treated with gemcitabine/platinum
Journal
Journal of Thoracic Oncology
Journal Volume
7
Journal Issue
6
Pages
973-981
Date Issued
2012
Author(s)
Abstract
Introduction: Elevated DNA-repair capacity has been related to chemoresistance of platinum doublet chemotherapy in non-small-cell lung cancer (NSCLC). We evaluated whether single nucleotide polymorphisms of DN-repair genes excision repair cross-complementing group 1 (ERCC1), ERCC2, x-ray repair cross-complementing group 1 (XRCC1), XRCC3, and RRM1 associate with treatment outcome in NSCLC patients receiving gemcitabine plus platinum as their first-line chemotherapy. METHODS: Genotyping for eight polymorphisms in five DNA-repair genes was performed with the GenomeLab nucleotide polymorphismstream Genotyping System in 62 advanced NSCLC patients in a training set and 45 patients in a validation set treated with gemcitabine/platinum. RESULTS: In the training set, the wild-type genotype of XRCC1 Arg399Gln (G/G) was associated with decreased median overall survival (OS) (22 months, 95% confidence interval [CI], 10-34 months versus not reached, log-rank test, p = 0.005) than those carrying variant genotypes (G/A+A/A). In addition, there was a statistically significant longer median OS in patients carrying wild-type ERCC2 Asp312Asn genotype (G/G) (51 months, 95% CI, 19-82 months versus 10 months, log-rank test, p < 0.001) than those carrying heterozygous variant genotypes (G/A). In the multivariate Cox model, we found a significant effect of XRCC1 Arg399Gln (G/A+A/A versus G/G, hazard ratio [HR] 0.290; 95%CI, 0.12-0.705, p = 0.006) and ERCC2 Asp312Asn (G/A versus G/G, HR 14.04; 95% CI, 2.253-87.513, p = 0.005) polymorphisms on patients' OS. In the validation set, only XRCC1 399 CONCLUSIONS: Genetic polymorphism of XRCC1 Arg399Gln may be a candidate for contributing interindividual difference in the OS of gemcitabine/platinum- treated advanced NSCLC patients. Copyright ? 2012 by the International Association for the Study of Lung Cancer.
SDGs
Other Subjects
arginine; asparagine; aspartic acid; bevacizumab; carboplatin; cisplatin; epidermal growth factor receptor kinase inhibitor; excision repair cross complementing protein 1; gemcitabine; glutamine; lysine; methionine; oxaliplatin; ribonucleotide reductase; ribonucleotide reductase subunit M1; threonine; unclassified drug; xeroderma pigmentosum group D protein; XRCC1 protein; XRCC3 protein; adult; advanced cancer; aged; article; cancer combination chemotherapy; cancer survival; DNA repair; female; genetic variability; genotype; heterozygosity; human; lung non small cell cancer; major clinical study; male; overall survival; priority journal; single nucleotide polymorphism; treatment outcome; validation process; wild type
Publisher
Lippincott Williams and Wilkins
Type
journal article