Jeng Jen-Eing, Tsai Huey-Ru, Chuang Lee-Yea, Tsai Jung-Fa, Lin Zu-Yau, Hsieh Min-Yuh, Chen Shin-Chern, Chuang Wan-Lung, Wang Liang-Yen, Yu Ming-Lung, Dai Chia-Yen, Chang Jan-Gowth
From Department of Laboratory Medicine (JEJ, JGC), and Internal Medicine (JFT, ZYL, MYH, SCC, WLC, LYW, MLY, CYD), Kaohsiung Medical University Hospital; and Department of Laboratory Medicine (JEJ, JGC), Internal Medicine (JFT, ZYL, MYH, SCC, WLC, LYW, MLY, CYD), and Biochemistry (LYC), Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; and Department of Internal Medicine (HRT), Sin-Lau Christmas Hospital, Tainan, Taiwan.
Medicine (Baltimore). 2009 Nov;88(6):349-357. doi: 10.1097/MD.0b013e3181c10477.
We conducted a case-control study to assess the roles of tumor necrosis factor (TNF)-alpha polymorphisms, substance use habits, and chronic hepatitis B virus (HBV)/hepatitis C virus (HCV) infection on the risk for hepatocellular carcinoma (HCC). We enrolled 200 pairs of sex- and age-matched patients with HCC and unrelated healthy controls. TNF-alpha polymorphisms were detected with polymerase chain reaction and direct sequencing. Serum hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV) were detected. We used a structured questionnaire to obtain information about substance use habits.Multivariate analysis indicated that TNF308.2 allele (odds ratio [OR], 3.23; p = 0.011), habitual betel quid chewing (OR, 3.70; p = 0.011), HBsAg (OR, 23.62; p = 0.0001), and anti-HCV (OR, 38.73; p = 0.0001) were independent risk factors for HCC. Having at least 2 substance use habits was associated with risk for HCC. The more substance use habits, the higher the OR for HCC (p(for trend) = 0.0001). There were additive interactions among TNF308.2 allele, substance use habits, and chronic HBV/HCV infection. Multivariate analysis indicated that TNF308.2 allele (p = 0.001), cigarette smoking (p = 0.0001), and alcohol drinking (p = 0.0001) were independent risk factors for habitual betel quid chewing. Moreover, patients harboring the TNF308.2 allele and/or those with habits of substance use had low serum albumin concentration and platelet count (each p = 0.0001). In conclusion, there are independent and additive interactive effects among the TNF308.2 allele, substance use habits, and chronic HBV/HCV infection on the risk for HCC. Substance use habits or carrying the TNF308.2 allele correlates with disease severity and hepatic fibrosis, which may contribute to higher risks for HCC.
我们开展了一项病例对照研究，以评估肿瘤坏死因子（TNF）-α基因多态性、物质使用习惯以及慢性乙型肝炎病毒（HBV）/丙型肝炎病毒（HCV）感染在肝细胞癌（HCC）风险中的作用。我们纳入了200对年龄和性别匹配的HCC患者及无关健康对照。采用聚合酶链反应和直接测序检测TNF-α基因多态性。检测血清乙型肝炎表面抗原（HBsAg）和抗HCV抗体（抗-HCV）。我们使用结构化问卷获取物质使用习惯信息。多因素分析表明，TNF308.2等位基因（比值比[OR]，3.23；p = 0.011）、习惯性嚼槟榔（OR，3.`70；p = 0.011）、HBsAg（OR，23.62；p = 0.0001）和抗-HCV（OR，38.73；p = 0.0001）是HCC的独立危险因素。具有至少2种物质使用习惯与HCC风险相关。物质使用习惯越多，HCC的OR越高（趋势p = 0.0001）。TNF308.2等位基因、物质使用习惯和慢性HBV/HCV感染之间存在相加交互作用。多因素分析表明，TNF308.2等位基因（p = 0.001）、吸烟（p = 0.0001）和饮酒（p = 0.0001）是习惯性嚼槟榔的独立危险因素。此外，携带TNF308.2等位基因的患者和/或有物质使用习惯的患者血清白蛋白浓度和血小板计数较低（各p = 0.0001）。总之，TNF308.2等位基因、物质使用习惯和慢性HBV/HCV感染在HCC风险中存在独立和相加的交互作用。物质使用习惯或携带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。
