细胞色素P450 2E1基因与鼻咽癌易感性分析

Association between genetic polymorphism of human cytochromeP450 2E1 gene and susceptibility to nasopharyngeal carcinoma

目的：为了探讨鼻咽癌的病因发病机理，进一步揭示鼻咽癌的易感因素，本文进行了细胞色素Ｐ４５０２Ｅ１（ＣＹＰ２Ｅ１） 基因多态性与鼻咽癌易感性关系的研究。方法：采用病例－ 对照分子流行病学方法分析１０５ 例鼻咽癌患者和９３ 例正常人体细胞ＣＹＰ２Ｅ１ 基因型。结果： 发现ＲｓａＩ和ＰｓｔＩ识别的ＣＹＰ２Ｅ１ 基因纯合子突变型（Ｃ２／Ｃ２） 在鼻咽癌人群为５－７ ％ ，显著高于正常人群（１－１％ ） 分布（χ２ ＝ ４－８６ ，Ｐ＜ ０－０５） ；携带Ｃ２／Ｃ２ 基因型个体发生鼻咽癌的危险性比携带其它基因型个体高５ 倍左右。结论：ＣＹＰ２Ｅ１ 基因的多态性可能是鼻咽癌易感的因素之一。

Objective: Nasopharyngeal carcinoma(NPC) have been thought to be linked to nitrosamine exposure,while cytochrome P450 2E1(CYP2E1) is responsible for the metabolic activation of precarcinogens such as nitrosamines. The object of this paper is to investigate the possible role of CYP2E1 genetic polymorphisms in the etiology of NPC. Methods:Using the case control molecular epidemiologic method,we detected a restriction fragment length polymorphism (RFLP) of human CYP2E1 gene for the restriction endonuclease Rsa Ιand PstΙon DNA isolated from blood samples from NPC cases(105)and normal control (93). Results: Among healthy control, the allelic frequency of wild type and variant type CYP2E1 were 81%and 19%,respectively,using RsaΙand PstΙenzyme digestion, while genotype frequency of wildtype homozygotes (C1/C1), heterozygotes (C1/C2) and variant homozygotes (C2/C2) were 63 4%, 35 5%and 1 1%,respectively,for the normal control and 68 6%,25 7%and 5 7%,respectively,for the NPC cases. There was a significant difference between case and control which carried CYP2E1 gene C2/C2 genotype identified by RsaΙand PstΙ(χ2=4 86,P< 0 05). As compared with individuals who were homozygous for the wild type(C1/C1) and heterozygous CYP2E1 gene(C1/C2),those found to be homozygous for the variant form of gene were 5 fold excess risk of developing NPC (95%confident interval=0 57-41 90).Conclusion : The genetic polymorphisms of CYP2E1 gene may be one of the susceptible causes to NPC.