广西壮族人群肝癌家族聚集与细胞色素P450 2E1基因多态性等因素关系的研究

Study on the relationship between familial clustering of hepatocellular carcinoma and polymorphism of cytochrome P450 2E1 gene in Zhuang population, Guangxi

目的探讨广西壮族人群肝癌高发家族聚集与细胞色素P450 2E1（CYP2E1）基因多态性等因素的关系。方法在广西某肝癌高发现场壮族人群中，对10个肝癌高发家族成员（共91名）和10个无癌对照家族成员（共102名），采集外周血标本，以多聚酶链反应-限制性片段长度多态性技术（PCR.RFLP），分析所有研究对象CYP2E1基因Rsa I位点基因型及等位基因的分布频率；并用ELISA法检测HBsAg。肝癌相关因素的暴露情况则应用统一问卷进行调查。结果肝癌高发家族成员CYP2E1基因RsaI位点C1／c1、c1／c2基因型频率分别为63.7％和36.3％；在对照家族成员中，相应的频率分别为48.0％和52.0％（OR=1.901，95％Ci：1.067-3.387）；两组成员Rsa I位点基因型分布的差异有统计学意义（X^2=4.797，P=0.029）。非条件logistic回归分析结果显示，当地肝癌家族聚集的主要危险因素，按其危险度由高至低排列依次为：以玉米为主食、HBsAg携带、CYP2E1 c1／c1型。结论在广西壮族人群中，肝癌的家族聚集与家族成员的CYP2E1基因Rsa I多态性的分布，有肯定的统计学关系；CYP2E1基因Rsa I多态性的分布不是引起肝癌家族聚集的惟一因素，也不是首要因素，与其他一些因素的综合作用更为重要。

Objective To study the relationship between familial clustering of hepatocellular carcinoma （HCC） and the polymorphism of cytochrome P450 2E1 gene （CYP2E1） as well as of other relevant risk factors to the cancer. Methods Peripheral blood samples were collected from 91 members of 10 HCC clustering families and 102 of 10 control families, among Zhuang population, in Guangxi. The area had been with high incidence rate of HCC. Genotypes and allele frequencies of CYP2EI Rsa I site were determined by polymerase chain reaction, combined with restriction fragment length polymorphism method （PCR-RFLP）. Serum HBsAg was tested by means of ELISA. Data on relevant risk factors of the cancer were collected as well, through a unique questionnaire. Results Frequencies of c1/c1 and c1/c2 genetypes of CYP2E1 Rsa I site were 63.7% and 36.3%, respectively, in the members of families with cancer clustering phenomena. In the members of the control families, these two rates were 48.0% and 52.0%, respectively （OR= 1.901,95% CI： 1.067-3.387）. Difference of genotypes frequencies of CYP2E1 Rsa I site between the members in these two groups was statistically significant （Z2=4.797, P=0.029）. According to the results from non-condition logistic regression analysis, the major risk factors on familial clustering of HCC could be listed as： intake of corns, HBsAg carrying status and CYP2E1 cl/cl genotype. Conclusion The relationship seemed to exist between familial clustering of HCC and the frequencies of polymorphism of cytochrome P450 2E1 gene （CYP2E1）. The frequencies of CYP2E1 Rsa I site were neither the only nor the major factor, causing the familial clustering phenomenon of cancer. More possible, it was the affect of syntheses with the involvement of multiple factors.