CYP2E1 DraⅠ基因遗传多态性与青海省胃癌人群易感性的相关性研究

Correlation between genetic polymorphisms of CYP2E1 DraⅠ and susceptibility of gastric cancer in Qinghai province

背景与目的：胃癌是青海省最常见的恶性肿瘤和致死病因之一，生活环境中的前致癌物质需要经过体内代谢酶代谢并转化为致癌物质，CYP2E1是人体内重要的I相代谢酶，已知CYP2E1在不同人种、不同地区存在基因多态性，本研究旨在探讨CYP2E1 DraI基因遗传多态性与青海地区人群胃癌易感性的相关性。方法：采用病例对照分子流行病的研究方法，并用数字表法随机选取世居青海的胃癌患者120例（胃癌组）和与之匹配的同期世居青海的健康体检者120例（对照组），应用PCR-RFLP技术对两组人群CYP2E1 DraI位点的不同基因型及等位基因进行检测，分析其在两组间的分布特征。结果：CYP2E1基因DraI位点各不同基因型（包括C／C、C／D、D／D）在胃癌组和对照组中的分布频率分别为58．33％、35．00％、6．67％和58．33％、38．34％、3．33％，两组差异无统计学意义（P分别=1．00、0．59、0．24）；CYP2E1基因DraI位点的等位基因（C和D）在胃癌组和对照组中的分布频率为75．83％、24．17％和77．50％、22．50％，两组差异无统计学意义钟=0．19，P=0．67）；CYP2E1基因DraI多态性位点突变基因型（C／D、D／D）与高／高中分化胃腺癌的发生相关（X^2=4．49，P=0．03，0R=3．5，95％CI：1．04-11．80），是青海地区发生高／高中分化胃腺癌的危险因素；CYP2E1 DraI野生纯合子（C／C）与低分化胃腺癌的发生相关（X^2=3．97，P=0．049，0R=0．54，95％CI：0．29-1．00），是发生低分化胃腺癌的危险因素。结论：CYP2E1 DraI基因遗传多态性与青海地区人群不同分化程度胃腺癌易感性存在一定相关性，携带CYP2E1 DraI野生型纯合子（C／C）者易发生低分化胃腺癌，携带突变纯合子（D／D）和突变杂合子（C／D）者易发生高分化及高中分化肖腺癌。

Background and purpose： Gastric cancer is the most common malignant tumor and the leading cause of death in Qinghai province. The possible chemical procarcinogens in our living environment must be activated and transformed ultimately into carcinogens by CYP2E1 of cytochrome, one of the most important I phase metabolic enzymes in human body, and also the genetic polymorphisms of CYP2E1 are reportedly in different ethnic groups and in different regions. The aim of this study was to investigate the correlation between genetic polymorphisms of CYP2E1 Dra I and the susceptibility of gastric cancer in Qinghai province. Methods： A case control study was performed with the molecular epidemiological methods. A total of 120 gastric cancer cases （as the gastric cancer group） and 120 healthy people （as the control group） were randomly selected from affiliated hospital of Qinghai University from Jan. 2010 to Apr. 2012, and all of the individuals were living in Qinghai province. The genotypes and alleles ofCYP2E1 Dra I in both of the above groups were detected by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）, and then the outcome was analyzed statistically, Results： The distribution frequency of CYP2E1 Dra I genotypes （including C/C, C/D, D/D） was 58.33%, 35.00% and 6.67% in the patient group respectively, 58.33%, 38.34% and 3.33% in the control group respectively, which showed no significant differences between the two groups （the value of P were 1.00, 0.59 and 0.24, respectively）. The distribution frequency of CYP2E1 Dra I alleles （including C and D） was 75.83% and 24.17% in the patient group respectively, meanwhile, 77.50% and 22.50% in the control group respectively, which also showed no significant difference between the two groups （3（2=0.19, P=0.67）. Interestingly, the mutant genotypes （C/D, D/D） of CYP2E1 Dra I were associated with the well and well-moderately differentiated gastric adenocarcinoma in a way （;（2=4.49 and P=0.03; OR=3.5 and 95%CI： 1.04-11.80）, and it was also demonstrated that the mutant genotypes （C/D, D/D） were the risk factors for the oncogenesis of well and well- moderately differentiated gastric adenocarcinoma; The wild homozygote （C/C） of CYP2E1 Dra I was related to poorly differentiated gastric adenocarcinoma （;（2=3.97 and P=0.049; OR=0.54 and 95%CI： 0.29-1.00 ）, and it was still revealed that the wild homozygote （C/C） of CYP2E1 Dra I was the risk factor for the tumorigenesis of poorly differentiated gastric adenocarcinoma. Conclusion： The genetic polymorphisms of CYP2E1 Dra I are to some extent associated with the susceptibility of different differentiated gastric adenocarcinoma in Qinghai province, furthermore, carriers of wild homozygote （C/C） of CYP2E1 Dra I are relatively prone to the risk factor to the occurrence of poorly differentiated gastric adenocarcinoma, and carriers of mutant homozygote （D/D） and mutant heterozygote （C/D） are also liable to occur the well/well-moderated differentiated gastric adenocarcinoma in Qinghai province.