Clinical Medicine College of Southeast University, Nanjing 210009, China.
Acta Biochim Biophys Sin (Shanghai). 2010 May 15;42(5):311-7. doi: 10.1093/abbs/gmq023.
Platinum-based chemotherapeutics are the most common regimens for advanced non-small-cell lung cancer (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 singlenucleotide polymorphisms (SNPs) in human mutS homolog 2 (hMSH2) and the human mutL homolog 1 (hMLH1) were associated with the tumor response in advanced NSCLC patients received platinum-based chemotherapy in Chinese population. Totally, 96 patients with advanced NSCLC were routinely treated with cisplatin- or carboplatin-based chemotherapy. The three-dimensional (3D), polyacrylamide gel-based DNA microarray method was used to evaluate the genotypes of hMSH2 gIVS12-6T/ C and hMLH1-1151T/A with peripheral lymphocytes. We found that there was a significantly increased chance of treatment response to platinum-based chemotherapy with the hMSH2 gIVS12-6T/C polymorphism. The 3D polyacrylamide gel-based DNA microarray method is 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，在临床治疗中很难确定铂类耐药性。遗传因素被认为是药物疗效的重要决定因素。在这项研究中，我们调查了人类错配修复蛋白 2（hMSH2）和人类错配修复蛋白 1（hMLH1）中的单核苷酸多态性（SNPs）是否与接受铂类化疗的中国晚期 NSCLC 患者的肿瘤反应有关。总共 96 例晚期 NSCLC 患者常规接受顺铂或卡铂为基础的化疗。采用三维（3D）、聚丙烯酰胺凝胶 DNA 微阵列法评估外周血淋巴细胞中 hMSH2 gIVS12-6T/C 和 hMLH1-1151T/A 的基因型。我们发现 hMSH2 gIVS12-6T/C 多态性与铂类化疗的治疗反应有显著增加的机会。基于 3D 聚丙烯酰胺凝胶的 DNA 微阵列法准确、高通量且廉价，特别适合于人群中 SNP 基因分型的大规模应用。
