https://scholars.lib.ntu.edu.tw/handle/123456789/161265
標題: | Genetic Polymorphism of XRCC1 Arg399Gln Is Associated With Survival in Non-Small-Cell Lung Cancer Patients Treated With Gemcitabine/Platinum | 作者: | Liao, Wei-Yu | 關鍵字: | Non-small-cell lung cancer;DNA repair;Single nucleotide polymorphism | 公開日期: | 2012 | 卷: | 7 | 期: | 6 | 起(迄)頁: | 973-981 | 來源出版物: | J. Thorac. Oncol. | 摘要: | 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 polymorphism-stream 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 polymorphisms showed significant effect on patients' OS (G/A+A/A vs. G/G, HR 0.474; 95% CI, 0.245-0.915, p = 0.026) Conclusions: Genetic polymorphism of XRCC1 Arg399Gln may be a candidate for contributing interindividual difference in the OS of gemcitabine/platinum-treated advanced NSCLC patients. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/258850 |
顯示於: | 腫瘤醫學研究所 |
檔案 | 描述 | 大小 | 格式 | |
---|---|---|---|---|
index.html | 23.18 kB | HTML | 檢視/開啟 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。