He Yongchao, Zhang Hongwei, Yin Jianhua, Xie Jiaxin, Tan Xiaojie, Liu Shijian, Zhang Qian, Li Chengzhong, Zhao Jun, Wang Hongyang, Cao Guangwen
Department of Epidemiology, the 1st Affiliated Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
Carcinogenesis. 2009 Nov;30(11):1916-22. doi: 10.1093/carcin/bgp226. Epub 2009 Oct 1.
Genetic predisposition of nuclear factor-kappa B (NF-kappaB)-signaling pathways linking inflammation to hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) remains unresolved. We conducted a case-control study to determine the associations of the polymorphisms within the promoter regions of NFKB1 encoding NF-kappaB1 and NFKBIA encoding IkappaBalpha with the development of HCC. A total of 404 healthy controls, 482 non-HCC subjects with HBV infection and 202 patients with HCC were included. NFKB1 -94ATTG2 allele and GG allele in the 3'-untranslated region of NFKBIA were more prevalent in HCC patients than in the healthy controls. NFKBIA -826CT and NFKBIA -881AG allelic carriages were more prevalent in HCC patients than in the non-HCC subjects with HBV infection. The estimated haplotype frequency of NFKBIA promoter -881G-826T-519C was significantly higher in the patients with HCC than in the HBV-infected subjects without HCC (odds ratio = 3.142, P = 0.002). As compared with the HBV-infected subjects without HCC, NFKBIA -826 T and NFKBIA -881AG allelic carriages were only associated with HCC risk in the subjects with HBV genotype C. The association of NFKBIA -881AG allelic carriage with HCC risk was not affected by liver cirrhosis (LC) status, alanine aminotransferase level and hepatitis B e antigen status. By multivariate regression analysis, NFKB1 -94ATTG2, NFKBIA -826T, NFKBIA -881AG and HBV genotype C were independently associated with an increased risk of HCC. In conclusion, NFKB1 -94ATTG2 allele and haplotype -881G-826T-519C in NFKBIA promoter were associated with hepatocarcinogenesis. NFKBIA -826T and -881AG were associated with the risk of HCC in the subjects infected with HBV genotype C.
将炎症与乙型肝炎病毒（HBV）诱导的肝细胞癌（HCC）联系起来的核因子-κB（NF-κB）信号通路的遗传易感性仍未得到解决。我们进行了一项病例对照研究，以确定编码NF-κB1的NFKB1和编码IκBα的NFKBIA启动子区域内的多态性与HCC发生之间的关联。总共纳入了404名健康对照者、482名HBV感染的非HCC受试者和202名HCC患者。NFKB1 -94ATTG2等位基因和NFKBIA 3'-非翻译区的GG等位基因在HCC患者中比在健康对照者中更常见。NFKBIA -826CT和NFKBIA -881AG等位基因携带者在HCC患者中比在HBV感染的非HCC受试者中更常见。NFKBIA启动子-881G-826T-519C的估计单倍型频率在HCC患者中显著高于未患HCC的HBV感染受试者（优势比=3.142，P = 0.002）。与未患HCC的HBV感染受试者相比，NFKBIA -826 T和NFKBIA -881AG等位基因携带者仅在HBV基因型C的受试者中与HCC风险相关。NFKBIA -881AG等位基因携带者与HCC风险的关联不受肝硬化（LC）状态、丙氨酸转氨酶水平和乙肝e抗原状态的影响。通过多变量回归分析，NFKB1 -94ATTG2、NFKBIA -826T、NFKBIA -881AG和HBV基因型C与HCC风险增加独立相关。总之，NFKB1 -94ATTG2等位基因和NFKBIA启动子中的单倍型-881G-826T-519C与肝癌发生相关。NFKBIA -826T和-881AG与HBV基因型C感染受试者的HCC风险相关。
