Polymorphisms in XRCC1 and XPG and response to platinum-based chemotherapy in advanced non-small cell lung cancer patients.
Platinum-based chemotherapeutics is the most common regimens for advanced NSCLC patients. However, it is difficult to identify platinum resistance in clinical treatment. Genetic factors are thought to represent important determinants of drug efficacy. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in Xeroderma pigmentosum group G (XPG) and X-ray repair cross complementing group 1 (XRCC1) were associated with the tumor response in non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy in Chinese population. Totally 82 patients with advanced NSCLC were routinely treated with cisplatin or carboplatin-based chemotherapy, and clinical response was evaluated after 2-3 cycles. And 3D (three dimensions) polyacrylamide gel-based DNA microarray method was used to evaluate the genotypes of XRCC1 194 Arg/Trp, XRCC1 399Arg/Gln, XPG 46His/His and XPG 1104His/Asp in DNA from peripheral lymphocytes. We found that there was a significantly increased chance of treatment response to platinum-based chemotherapy with the XRCC1 194Arg/Trp genotype (odds ratio 0.429; 95% CI 0.137-1.671; P=0.035). The polymorphism of XPG 46His/His was found to be associated with clinical response in NSCLC patients P=0.047, not detected between chemotherapy response and SNPs of XRCC1 399Arg/Gln or XPG 1104His/Asp (P=0.997 0.561, respectively). Our study showed that the polymorphic status of XRCC1 194Arg/Trp might be a predictive marker of treatment response for advanced NSCLC patients and those of XPG His46His was associated with susceptibility of chemotherapy. The 3D polyacrylamide gel-based DNA microarray method was accurate, high-throughput and inexpensive, especially suitable for a large scale of SNP genotyping in population.
Sun
Xinchen
X
Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, China.
Li
Fan
F
Sun
Ning
N
Shukui
Qin
Q
Baoan
Chen
C
Jifeng
Feng
F
Lu
Cheng
C
Zuhong
Lu
L
Hongyan
Cheng
C
YuanDong
Cao
C
Jiazhong
Ji
J
Yingfeng
Zhou
Z
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016190:Carboplatin / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D002945:Cisplatin / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics*; D000076105:X-ray Repair Cross Complementing Protein 1; D000099250:DNA Excision Repair Protein ERCC-5
D000970:Antineoplastic Agents; D016190:Carboplatin; D002945:Cisplatin; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D000076105:X-ray Repair Cross Complementing Protein 1; D000099250:DNA Excision Repair Protein ERCC-5; C000619371:XRCC1 protein, human