Sharma Anita, Das Bhudev Chander, Sehgal Ashok, Mehrotra Ravi, Kar Premashish, Sardana Sarita, Phukan Rup, Mahanta Jagdish, Purkayastha Joydeep, Saxena Sunita, Kapur Sujala, Chatterjee Indranil, Sharma Joginder Kumar
Division of Molecular Diagnostics, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector 39, Noida, 201301, India.
Tumour Biol. 2013 Oct;34(5):3249-57. doi: 10.1007/s13277-013-0897-6. Epub 2013 Jun 8.
Glutathione transferases, a super family of dimeric phase II metabolic enzymes play a vital role in biotransformation of many substances. This study evaluates the influence of genetic polymorphism of GSTM1 and GSTT1 gene loci on esophageal cancer risk in Assam and Delhi from India. DNA from blood samples of esophageal cancer cases (203,112) and controls (286,150) from Assam and Delhi, respectively, were extracted. GSTM1 and GSTT1 polymorphisms were analyzed by multiplex PCR procedure. Differences in proportions were tested using Pearson's chi-square test with odds ratio (OR) and 95 % confidence interval (CI). Risk of esophageal cancer was approximately twice in individuals having homozygous GSTM1 (OR-2.1, 95 % CI, 1.44-3.13) and GSTT1 null genotypes (OR-1.7,95 % CI, 0.99-2.77) in Assam, and around three times in GSTT1 null genotype (OR-2.9, 95 % CI, 1.56-5.27) in Delhi population. GSTM1 null genotype seems to play a protective role (OR-0.7, 95 % CI, 0.39-1.27) in Delhi. A significant association of GSTM1 null genotype with esophageal cancer was observed in a younger age group in Assam (OR-2.7, 95 % CI, 1.48-5.01), and in Delhi population association was observed in smokers with GSTT1 null genotype (OR-2.5, 95 % CI, 1.04-6.07), and alcoholics having GSTM1 null genotype (OR-2.6, 95 % CI, 0.99-6.77). Significant association of GSTM1 null genotype in Assam was observed between cancer cases and controls in fermented betel nut chewers only (OR-2.8, 95 % CI, 1.19-6.72), whereas, smoking and alcohol failed to show any correlation with GSTM1/GSTT1 genotypes. Cancer development is not only due to exogenous or endogenous carcinogens but depends on their interaction with genes that are involved in the detoxification of these carcinogens.
谷胱甘肽转移酶是二聚体II相代谢酶的一个超家族，在许多物质的生物转化中起着至关重要的作用。本研究评估了印度阿萨姆邦和德里地区GSTM1和GSTT1基因座的基因多态性对食管癌风险的影响。分别从阿萨姆邦和德里地区的食管癌病例（203例）和对照（286例）的血液样本中提取DNA。通过多重PCR程序分析GSTM1和GSTT1基因多态性。使用Pearson卡方检验及比值比（OR）和95%置信区间（CI）来检验比例差异。在阿萨姆邦，GSTM1纯合子（OR = 2.1，95% CI：1.44 - 3.13）和GSTT1无效基因型（OR = 1.7，95% CI：0.99 - 2.77）的个体患食管癌的风险约为两倍；在德里人群中，GSTT1无效基因型个体的风险约为三倍（OR = 2.9，95% CI：1.56 - 5.27）。在德里，GSTM1无效基因型似乎起到了保护作用（OR = 0.7，95% CI：0.39 - 1.27）。在阿萨姆邦的年轻年龄组中，观察到GSTM1无效基因型与食管癌存在显著关联（OR = 2.7，95% CI：1.48 - 5.01）；在德里人群中，在GSTT1无效基因型的吸烟者（OR = 2.5，95% CI：1.04 - 6.07）和GSTM1无效基因型的酗酒者中观察到关联（OR = 2.6，95% CI：0.99 - 6.77）。仅在阿萨姆邦咀嚼发酵槟榔的人群中，观察到癌症病例与对照之间GSTM1无效基因型存在显著关联（OR = 2.8，95% CI：1.19 - 6.72），而吸烟和饮酒与GSTM1/GSTT1基因型未显示任何相关性。癌症的发生不仅归因于外源性或内源性致癌物，还取决于它们与参与这些致癌物解毒的基因之间的相互作用。
