Polymorphisms in hMSH2 and hMLH1 and response to platinum-based chemotherapy in advanced non-small-cell lung cancer patients  

作　　者：Hongyan Cheng Ning Sun Xinchen Sun Baoan Chen Fan Li Jifeng Feng Lu Cheng Yuandong Cao 

机构地区：[1]Clinical Medicine College of Southeast University, Nanjing 210009, China [2]Zhongda Hospital, Southeast University, Nanjing 210009, China [3]Jiangsu Cancer Hospital, Nanjing 210009, China [4]Department of Oncology, Jiangsu Province Hospital, Nanjing 210029, China [5]State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China

出　　处：《Acta Biochimica et Biophysica Sinica》2010年第5期311-317,共7页生物化学与生物物理学报（英文版）

摘　　要：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 single- nucleotide 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 hMLHI-I151T/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 poly- acrylamide gel-based DNA microarray method is accurate, high-throughput, and inexpensive, especially suitable for a large scale of SNP genotyping in population.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 single- nucleotide 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 hMLHI-I151T/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 poly- acrylamide gel-based DNA microarray method is accurate, high-throughput, and inexpensive, especially suitable for a large scale of SNP genotyping in population.

关 键 词：single-nucleotide polymorphism gene-chip/microarray non-small-cell lung （NSCLC） chemotherapy （SNP） cancer 

分 类 号：Q346.5[生物学—遗传学] S852.43[农业科学—基础兽医学]