NF-κB1和NF-κBIα基因多态性与HBsAg阳性原发性肝癌易患性的关系

Relationship between polymorphism of NF-κB1 and NF-κBIα and susceptibility to hepatitis B virus-associated hepatocellular carcinoma:a case-control study

目的:探讨NF-κB1和NF-κBIα基因多态性与乙肝表面抗原(HBsAg)阳性原发性肝细胞癌(hepatocellular carcino-ma,HCC)易患性之间的关系。方法:采用限制性片段长度多态性-聚合酶链反应(RFLP-PCR)方法检测乙肝表抗阳性HCC患者、慢性肝炎患者(CHB)、健康对照组的NF-κB1和NF-κBIα基因多态性。应用多因素Logistic回归综合分析年龄、性别、吸烟、饮酒及各位点基因型与肝癌易感性之间的关系。结果:HCC组中NF-κB1 ATTG2/ATTG2基因型频率明显高于健康对照组(OR=2.21,95%CI 1.25～3.88);以同时携带各位点野生型携带者为参照,健康对照组中同时携带NF-κB1 ATTG2/AT-TG2基因型和NF-κBIαGG基因型的个体患肝癌的危险性明显增高(OR=2.94,95%CI 1.03～8.44);携带NF-κB1 ATTG2/ATTG2基因型的肝炎患者患肝癌的危险性增高(OR=2.31,95%CI 1.22～4.38);多因素分析结果显示:男性患肝癌的危险性是女性的2.01倍(95%CI 1.19～3.41);吸烟者患肝癌的危险性是不吸烟者的1.79倍(95%CI 1.04～3.07);饮酒者患肝癌的危险性是不饮酒者的2.58倍(95%CI 1.50～4.43);NF-κB1 ATTG2/ATTG2基因型携带者患肝癌的危险性是野生型NF-κB1 ATTG1/ATTG1携带者的2.17倍(95%CI 1.23～3.85)。结论:NF-κB1 ATTG2/ATTG2基因型是原发性肝癌的危险因素,与NF-κBIα的GG基因型之间存在交互作用;性别、吸烟、饮酒也是肝癌的危险因素。

Objective：To explore the association between polymorphisms of NF-κB1 and NF-κBIα and the risk of hepatitis B virus-associated heptocellular carcinoma （HCC）. Methods： The genetic polymorphisms of NF-κB1 and NF-κBIα were detected using restriction fragment length polymorphism polymerase chain reaction （RFLP-PCR） in patients with the hepatitis B virus associated HCC, patients with chronic hepatitis B and healthy controls. Multivariate Logistic regression model was used to assess the association of the age, sex, smoking history, alcohol drinking, and site of genetic polymorphisms with the susceptibility to HCC. Results： The frequency of NF-κB1 （ATTG2/ATTG2） genotype was significantly higher in HCC group than in healthy controls （odd ratio [OR] =2.21, 95% CI 1.25-3.88）. Compared to the people who carried NF-κB1 （ATTG1/ ATTG1） and NF-κBIα （AA） genotype spontaneously, healthy controls who carried NF-κB1 （ATTG2/ATTG2） and NF-κBIα （GG） genotype had an increased risk for HCC （OR 2.94, 95% CI 1.03 8.44）. Chronic hepatitis B patients who carried NF-κB1 （ATTG2/ATTG2） genotype had an increased risk for HCC （OR= 2. 31, 95% CI 1. 22-4. 38）. Multivariate analysis showed increased risk in male HCC patients with chronic hepatitis B（OR=2.01, 95% CI 1.19 3.41）, in those who carried NF- κB1 （ATTG2/ATTG2） genotype （OR=2.17, 95%CI 1.23 3.85）, in those who had a smoking history （OR=1. 79, 95% CI 1.04-3.07）, and in those who had a drinking history （OR = 2. 58,95% CI 1. 50-4. 43）. Conclusion： Genotype NF-κB1 （ATTG2/ATTG2） is a risk factor of HCC, and it has a synergistic effect with NF-κBIα （GG） genotype in contributing to hepatocarcinogenesis. Smoking and alcohol drinking are also risk factors for HCC.