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谷胱甘肽S-转移酶P1(GSTP1)基因c.341C>T多态性增加口腔鳞状细胞癌风险。

GSTP1 c.341C>T gene polymorphism increases the risk of oral squamous cell carcinoma.

作者信息

Rajesh Deepa, Balakrishna Sharath, Azeem Mohiyuddin S M, Suresh T N, Moideen Kutty A V

机构信息

Department of Cell Biology and Molecular Genetics, Sri Devaraj Urs Academy of Higher Education and Research, Kolar, India.

Department of Otorhinolaryngology, Sri Devaraj Urs Medical College, Kolar, India.

出版信息

Mutat Res Genet Toxicol Environ Mutagen. 2018 Jul;831:45-49. doi: 10.1016/j.mrgentox.2018.04.006. Epub 2018 Apr 30.

Abstract

Glutathione S Transferases (GST) are anti-oxidant enzymes involved in detoxification of cellular and exogenous carcinogens and oxidative products of reactive oxygen species. Genetic polymorphisms can attenuate the detoxification capacity of GST and consequently increase the susceptibility to carcinogenesis. There are eight classes of GST enzymes of which pi subtype is the predominant form expressed in the oral mucosa. c.341C > T single nucleotide polymorphism (rs1138272) in GSTP1 gene, is a functional variation that reduces the enzymatic activity of GST pi. We carried out a 1:2 case-control study involving 270 individuals to determine the association of c.341C > T variation with the risk of oral squamous cell carcinoma. GSTP1 c.341C > T variation was genotyped by PCR-RFLP method. GST pi expression in the tumour sample was determined by immunohistochemistry. Tobacco consumption was the major risk factor among cancer patients. The odds ratio for the risk of oral squamous cell carcinoma in individuals with the minor allele was 4.5 (0.95 CI = 2.3-8.9; P = 0.000004). The genotype was found to follow dominant mode of inheritance (OR 4.4 [0.95 CI = 2.1-9.2]; P = 0.00006). Our results support the conclusion that c.341C > T variation in GSTP1 increases the risk of OSCC in patients habituated to tobacco consumption.

摘要

谷胱甘肽S转移酶(GST)是抗氧化酶,参与细胞内和外源性致癌物以及活性氧氧化产物的解毒过程。基因多态性可减弱GST的解毒能力,从而增加致癌易感性。GST酶有八类,其中pi亚型是口腔黏膜中表达的主要形式。GSTP1基因中的c.341C>T单核苷酸多态性(rs1138272)是一种功能性变异,可降低GST pi的酶活性。我们开展了一项1:2病例对照研究,涉及270名个体,以确定c.341C>T变异与口腔鳞状细胞癌风险的关联。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对GSTP1的c.341C>T变异进行基因分型。通过免疫组织化学法测定肿瘤样本中GST pi的表达。吸烟是癌症患者的主要危险因素。携带次要等位基因的个体患口腔鳞状细胞癌的比值比为4.5(95%置信区间=2.3-8.9;P=0.000004)。发现该基因型遵循显性遗传模式(比值比4.4[95%置信区间=​2.1-9.2];P=0.00006)。我们的结果支持以下结论:GSTP1基因中的c.341C>T变异会增加有吸烟习惯患者患口腔鳞状细胞癌的风险。

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