Nissar Saniya, Sameer Aga Syed, Rasool Roohi, Chowdri Nissar A, Rashid Fouzia
Departments of Biochemistry and Clinical Biochemistry, University of Kashmir; Department of Immunology and Molecular Medicine, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India.
Department of Immunology and Molecular Medicine, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India; Department of Basic Medical Sciences, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, KSA.
Indian J Cancer. 2019 Jul-Sep;56(3):248-253. doi: 10.4103/ijc.IJC_11_18.
Glutathione-S-transferases (GSTs) are the most important phase II enzymes of the xenobiotic pathway responsible for the detoxification of carcinogens. GSTP1 gene polymorphisms are mostly associated with a lack or an alteration of enzymatic activity toward several substrates thus resulting in increased cancer susceptibility. GSTP1 promoter methylation is also frequently associated with tumor development or poor prognosis in a wide range of tumors.
In this study, we examined the role of genetic polymorphism and promoter methylation of GSTP1 gene in the context of modulation of risk of colorectal cancer (CRC) in Kashmiri population.
This study used tissue tumor samples (114) and blood samples from (160) patients with CRC and 200 blood samples from healthy donors. GSTP1 polymorphism was studied using polymerase chain reaction (PCR)-restriction fragment length polymorphism and methylation using methylation-specific PCR.
There was no significant association between GSTP1 I105V genotypes and the CRC (P>0.05). However, we found a significant association of the Val/Val variant genotype with the dwelling and smoking status (P-value < 0.05). Overall, the homozygous variant Val/Val genotype was associated with a modestly elevated risk for CRC (OR = 1.57; 95% CI = 0.67-3.57). Methyl-specific-PCR analysis revealed 25.4% methylation of the GSTP1 promoter in CRC cases and was not found to be statistically significantly associated with clinicopathological parameters of the CRC cases (P>0.05). Also, no significant associations of any of the three genotypes with promoter hypermethylation were observed.
We conclude that promoter hypermethylation in homozygous GSTP1 mutants did not elevate the risk of CRC in Kashmiri population.
谷胱甘肽 - S - 转移酶（GSTs）是外源性物质代谢途径中最重要的Ⅱ相酶，负责致癌物的解毒。GSTP1基因多态性大多与对几种底物的酶活性缺乏或改变有关，从而导致癌症易感性增加。GSTP1启动子甲基化也经常与多种肿瘤的肿瘤发生或预后不良相关。
在本研究中，我们在克什米尔人群中研究了GSTP1基因的遗传多态性和启动子甲基化在调节结直肠癌（CRC）风险中的作用。
本研究使用了114份组织肿瘤样本和160例CRC患者的血液样本以及200份健康供体的血液样本。使用聚合酶链反应（PCR）-限制性片段长度多态性研究GSTP1多态性，使用甲基化特异性PCR研究甲基化。
GSTP1 I105V基因型与CRC之间无显著关联（P>0.05）。然而，我们发现Val/Val变异基因型与居住和吸烟状况存在显著关联（P值<0.05）。总体而言，纯合变异Val/Val基因型与CRC风险适度升高相关（OR = 1.57；95%CI = 0.67 - 3.57）。甲基特异性PCR分析显示CRC病例中GSTP1启动子甲基化率为25.4%，且未发现与CRC病例的临床病理参数有统计学显著关联（P>0.05）。此外，未观察到三种基因型中的任何一种与启动子高甲基化有显著关联。
我们得出结论，在克什米尔人群中，纯合GSTP1突变体中的启动子高甲基化并未增加CRC风险。
