Jain Meenu, Kumar Shaleen, Rastogi Neeraj, Lal Punita, Ghoshal Uday C, Tiwari Anu, Pant Mohan C, Baiq Mirza Q, Mittal Balraj
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow-226014, India.
Cancer Lett. 2006 Oct 8;242(1):60-7. doi: 10.1016/j.canlet.2005.10.034. Epub 2005 Dec 7.
Glutathione S-transferases(GSTs) are detoxification enzymes that provide critical defense against carcinogens. Our hypothesis was that altered frequencies of GST genotypes and environmental exposures might be associated with increased susceptibility for the development of esophageal cancer. A total of 100 esophageal cancer patients and 137 age and gender matched healthy controls were analyzed for GST polymorphisms. Frequencies of GSTT1 null, GSTM1 null and GSTP1 genotypes did not differ between patients and controls. However, a two-fold risk was observed for GSTM1 null genotype in adenocarcinoma (OR(odds ratio) 2.1; 95% CI(confidence intervals)=0.53-8.6). Further, we used a case only design to study gene-environment interactions in esophageal cancer. In patients with smoking habits, GSTM1 null and GSTP1 ile/ile genotype were at higher risk for esophageal cancer (OR 1.5; 95% CI=0.50-4.4 and OR 1.3; 95% CI=0.40-3.5), respectively. A moderate risk for cancer was observed from alcohol usage along with GSTM1 null(OR 1.3; 95% CI=0.50-3.6) and GSTP1 val/val genotypes(OR 1.2; 95% CI=0.20-5.7). Interaction of GST genotypes with occupational exposure did not affect risk for esophageal cancer. These findings suggest that genetic polymorphisms of GSTT1, GSTM1, and GSTP1 are not associated with higher risk of esophageal cancer. However, interaction of smoking or alcohol with GSTM1 null or GSTP1 ile/ile moderately increases the risk for esophageal cancer in North Indian population.
谷胱甘肽S-转移酶（GSTs）是一种解毒酶，可对致癌物提供关键防御。我们的假设是，GST基因型频率的改变和环境暴露可能与食管癌发生易感性增加有关。对100例食管癌患者和137例年龄及性别匹配的健康对照者进行了GST多态性分析。患者和对照者之间GSTT1缺失、GSTM1缺失和GSTP1基因型的频率没有差异。然而，在腺癌中观察到GSTM1缺失基因型的风险增加了两倍（优势比（OR）2.1；95%置信区间（CI）=0.53-8.6）。此外，我们采用病例对照设计研究食管癌中的基因-环境相互作用。在有吸烟习惯的患者中，GSTM1缺失和GSTP1 ile/ile基因型患食管癌的风险较高（OR分别为1.5；95%CI=0.50-4.4和OR 1.3；95%CI=0.40-3.5）。饮酒与GSTM1缺失（OR 1.3；95%CI=0.50-3.6）和GSTP1 val/val基因型（OR 1.2；95%CI=0.20-5.7）一起观察到患癌的中度风险。GST基因型与职业暴露的相互作用不影响食管癌风险。这些发现表明，GSTT1、GSTM1和GSTP1的基因多态性与食管癌的高风险无关。然而，在北印度人群中，吸烟或饮酒与GSTM1缺失或GSTP1 ile/ile的相互作用会适度增加患食管癌的风险。
