Jeng Jen-Eing, Tsai Jung-Fa, Chuang Lee-Yea, Ho Mei-Shang, Lin Zu-Yau, Hsieh Min-Yuh, Chen Shin-Chern, Chuang Wan-Lung, Wang Liang-Yen, Yu Ming-Lung, Dai Chia-Yen, Chang Jan-Gowth
Department of Clinical Laboratory, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Neoplasia. 2007 Nov;9(11):987-92. doi: 10.1593/neo.07781.
BACKGROUND/AIMS: Host genetic factor and hepatic fibrosis may predispose to risk for hepatocellular carcinoma (HCC). This study aimed to assess the association between tumor necrosis factor (TNF) alpha polymorphism and hepatic fibrosis, and risk for HCC.
One hundred eight pairs of gender-matched and age-matched patients with HCC and unrelated healthy controls were genotyped for TNF308.2 and TNF238.2 alleles with polymerase chain reaction and direct sequencing.
The frequency of TNF308.1/TNF308.2 genotype in cases was higher than that in controls [odds ratio (OR) = 4.37]. Multivariate analysis indicated that TNF308.2 allele (OR = 3.23), hepatitis B surface antigen (OR = 17.17), and antibodies to hepatitis C virus (OR = 45.52) were independent risk factors for HCC. Surrogate markers for significant fibrosis implied that cases with the TNF308.2 allele have more advanced liver fibrosis. Moreover, multivariate analysis indicated that cirrhosis with Child-Pugh grade C, low serum albumin, and low platelet count were independent risk factors for carrying the TNF308.2 allele.
TNF308.2 allele carriage and chronic hepatitis B virus/hepatitis C virus infection are independent risk factors for HCC. Carriage of the TNF308.2 allele correlates with disease severity and hepatic fibrosis, which may contribute to a higher risk for HCC.
背景/目的：宿主遗传因素和肝纤维化可能易患肝细胞癌（HCC）。本研究旨在评估肿瘤坏死因子（TNF）α基因多态性与肝纤维化及HCC风险之间的关联。
采用聚合酶链反应和直接测序法对108对性别和年龄匹配的HCC患者及无关健康对照进行TNF308.2和TNF238.2等位基因基因分型。
病例组中TNF308.1/TNF308.2基因型的频率高于对照组[比值比（OR）=4.37]。多因素分析表明，TNF308.2等位基因（OR = 3.23）、乙肝表面抗原（OR = 17.17）和丙肝病毒抗体（OR = 45.52）是HCC的独立危险因素。显著纤维化的替代标志物表明，携带TNF308.2等位基因的病例肝纤维化程度更严重。此外，多因素分析表明，Child-Pugh C级肝硬化、低血清白蛋白和低血小板计数是携带TNF308.2等位基因的独立危险因素。
携带TNF308.2等位基因和慢性乙型肝炎病毒/丙型肝炎病毒感染是HCC的独立危险因素。携带TNF308.2等位基因与疾病严重程度和肝纤维化相关，这可能导致HCC风险更高。
