Ghatak Souvik, Yadav Ravi Prakash, Lalrohlui Freda, Chakraborty Payel, Ghosh Soumee, Ghosh Sudakshina, Das Madhusudan, Pautu Jeremy L, Zohmingthanga John, Senthil Kumar Nachimuthu
Department of Biotechnology, Mizoram University, Aizawl, Mizoram, India.
Department of Zoology, University of Calcutta, Kolkata, West Bengal, India.
Helicobacter. 2016 Dec;21(6):523-535. doi: 10.1111/hel.12308. Epub 2016 Mar 23.
The aim of this study was to evaluate the risk of gastric cancer associated with individual or combined glutathione S-transferases (GSTs) polymorphism and their interaction with environmental factors.
Genotyping by PCR was carried out for 80 cases and controls each for GSTM1, GSTT1, and GSTP1 polymorphism and mapped for gene-environment association studies. The samples were subjected to pathogen detection and GSTP1 expression for analyzing their association with different genotypes. Logistic regression analyses were conducted to compute the influence of both genetic and environmental factors for gastric cancer. MDR analysis was performed to assess the risk of gastric cancer by studying the gene-gene and gene-environment effect on the basis of GST genotyping and GSTP1 gene expression.
Infection with Helicobacter pylori and CagA+ strains was more frequent in patients with GSTM1/T1 null genotype. Intake of high fermented fat and smoked meat was found to be significantly associated with gastric cancer. The G/G, A/G (rs1695), and T/T (rs1138272) were found to be significantly associated with low expression of GSTP1 gene in cancer tissue.
Presence of H. pylori with CagA genotype showed significant individual effect with GSTT1 polymorphism as well as strong synergistic effect in gastric cancer risk. Majority of the gastric cancer samples showed significant negative expression in G/G, A/G (rs1695), and T/T (rs1138272) genotypes. This study shows that GST gene polymorphism was significantly relevant for determining the individual susceptibility to gastric cancer.
本研究旨在评估个体或联合谷胱甘肽S-转移酶（GSTs）多态性与胃癌风险的相关性及其与环境因素的相互作用。
对80例病例和80例对照进行GSTM1、GSTT1和GSTP1多态性的PCR基因分型，并绘制基因-环境关联研究图谱。对样本进行病原体检测和GSTP1表达分析，以分析它们与不同基因型的关联。进行逻辑回归分析以计算遗传和环境因素对胃癌的影响。基于GST基因分型和GSTP1基因表达，进行多因素降维分析（MDR）以评估胃癌风险，研究基因-基因和基因-环境效应。
GSTM1/T1基因缺失型患者感染幽门螺杆菌和CagA+菌株更为常见。发现高发酵脂肪和烟熏肉的摄入与胃癌显著相关。在癌组织中，发现G/G、A/G（rs1695）和T/T（rs1138272）与GSTP1基因的低表达显著相关。
CagA基因型幽门螺杆菌的存在与GSTT1多态性在胃癌风险中显示出显著的个体效应以及强烈的协同效应。大多数胃癌样本在G/G、A/G（rs1695）和T/T（rs1138272）基因型中显示出显著的阴性表达。本研究表明，GST基因多态性与确定个体对胃癌的易感性显著相关。
