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O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)密码子Leu84Phe和密码子Ileu143Val多态性对克什米尔山谷食管癌风险无影响。

Lack of influence of MGMT codon Leu84Phe and codon Ileu143Val polymorphisms on esophageal cancer risk in the Kashmir Valley.

作者信息

Shah Mohd A, Shaff Sheikh M, Lone Ghulam Nabi, Jan Syed Mudassar

机构信息

Department of Clinical Biochemistry, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India.

出版信息

Asian Pac J Cancer Prev. 2012;13(7):3047-52.

Abstract

The enzyme encoded by the MGMT gene is involved in the repair of alkylated lesions formed in DNA by carcinogenic nitrosamines. Since dietary items consumed by the Kashmiri population contain high concentrations of these agents, it is biologically plausible that MGMT polymorphic variants may be associated with their risk of esophageal cancer. The present study was performed to assess whether non-synonymous SNPS at codon Leu84Phe and codon Ileu143Val of the MGMT gene, close to the active site of the protein, might be linked to predisposition of Kashmiris to esophageal cancer. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism on 92 cases and 77 healthy controls. Codon 84 and codon 143 SNPs of the MGMT gene were not associated with any increase in risk. While the frequency of the Phe allele at codon 84 in cases was (0.16), slightly higher than controls (0.12), the difference was not statistically significant. Similarly, the frequency of Valine allele in cases at codon 143 (0.08) and controls (0.09) was nearly equal. Moreover, no significant association of MGMT genotypes with the clinicopatholgic variables of esophageal cancer patients was observed. In conclusion, MGMT variants at codon 84 and codon143 may not be involved in the susceptibility of the Kashmiri population to esophageal cancer.

摘要

MGMT基因编码的酶参与修复由致癌亚硝胺在DNA中形成的烷基化损伤。由于克什米尔人群食用的食物中含有高浓度的这些物质,MGMT基因多态性变体可能与其患食管癌的风险相关,这在生物学上是合理的。本研究旨在评估MGMT基因中靠近蛋白质活性位点的第84位密码子Leu84Phe和第143位密码子Ileu143Val处的非同义单核苷酸多态性(SNPs)是否可能与克什米尔人患食管癌的易感性有关。通过聚合酶链反应-限制性片段长度多态性方法对92例患者和77名健康对照进行基因分型。MGMT基因的第84位密码子和第143位密码子的SNPs与风险增加无关。虽然病例组中第84位密码子的Phe等位基因频率为(0.16),略高于对照组(0.12),但差异无统计学意义。同样,病例组中第143位密码子的Valine等位基因频率(0.08)与对照组(0.09)几乎相等。此外,未观察到MGMT基因型与食管癌患者临床病理变量之间存在显著关联。总之,第84位密码子和第143位密码子的MGMT变体可能不参与克什米尔人群患食管癌的易感性。

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