Sun Xinchen, Li Fan, Sun Ning, Shukui Qin, Baoan Chen, Jifeng Feng, Lu Cheng, Zuhong Lu, Hongyan Cheng, YuanDong Cao, Jiazhong Ji, Yingfeng Zhou
Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, China.
Lung Cancer. 2009 Aug;65(2):230-6. doi: 10.1016/j.lungcan.2008.11.014. Epub 2009 Jan 20.
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.
铂类化疗药物是晚期非小细胞肺癌(NSCLC)患者最常用的治疗方案。然而,在临床治疗中难以识别铂耐药性。遗传因素被认为是药物疗效的重要决定因素。在本研究中,我们调查了中国人群中接受铂类化疗的非小细胞肺癌(NSCLC)患者,其G组着色性干皮病(XPG)和X射线修复交叉互补组1(XRCC1)中的单核苷酸多态性(SNP)是否与肿瘤反应相关。总共82例晚期NSCLC患者接受了顺铂或卡铂为基础的常规化疗,在2 - 3个周期后评估临床反应。并采用基于三维(3D)聚丙烯酰胺凝胶的DNA微阵列方法评估外周血淋巴细胞DNA中XRCC1 194 Arg/Trp、XRCC1 399Arg/Gln、XPG 46His/His和XPG 1104His/Asp的基因型。我们发现,携带XRCC1 194Arg/Trp基因型的患者对铂类化疗的治疗反应机会显著增加(优势比0.429;95%可信区间0.137 - 1.671;P = 0.035)。发现XPG 46His/His多态性与NSCLC患者的临床反应相关(P = 0.047),未检测到化疗反应与XRCC1 399Arg/Gln或XPG 1104His/Asp的SNP之间存在关联(分别为P = 0.997、0.561)。我们的研究表明,XRCC1 194Arg/Trp的多态性状态可能是晚期NSCLC患者治疗反应的预测标志物,而XPG His46His的多态性与化疗敏感性相关。基于三维聚丙烯酰胺凝胶的DNA微阵列方法准确、高通量且成本低廉,特别适用于人群中大规模的SNP基因分型。