Independent and Additive Interactive Effects Among Tumor Necrosis Factor-α Polymorphisms, Substance Use Habits, and Chronic Hepatitis B and Hepatitis C Virus Infection on Risk for Hepatocellular Carcinoma
Independent and Additive Interactive Effects Among Tumor Necrosis Factor-α Polymorphisms, Substance Use Habits, and Chronic Hepatitis B and Hepatitis C Virus Infection on Risk for Hepatocellular Carcinoma
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DOI：
10.1097/md.0b013e3181c10477
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发表时间：
2009-11-01
期刊：
影响因子：
1.6
通讯作者：
Chang, Jan-Gowth
中科院分区：
文献类型：
--
作者：
Jeng, Jen-Eing;Tsai, Huey-Ru;Chang, Jan-Gowth
我们进行了一项病例对照研究，以评估肿瘤坏死因子（TNF）-α多态性、物质使用习惯和慢性B肝炎病毒（HBV）/丙型肝炎病毒（HCV）感染对肝细胞癌（HCC）风险的作用。我们招募了200对性别和年龄匹配的HCC患者和无关的健康对照。采用聚合酶链反应和直接测序法检测TNF-α基因多态性。检测血清B型肝炎表面抗原（HBsAg）和抗-HCV抗体（抗-HCV）。多因素分析显示TNF308.2等位基因与物质使用习惯相关，TNF308.2等位基因与物质使用习惯相关。（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。至少有2种药物使用习惯与肝癌风险相关。物质使用习惯越多，HCC的OR越高（p（趋势）= 0.0001）。TNF 308.2等位基因、物质使用习惯和慢性HBV/HCV感染之间存在加性交互作用。多因素分析显示TNF308.2等位基因（p = 0.001）、吸烟（p = 0.0001）2和饮酒（p = 0.0001）是咀嚼槟榔习惯的独立危险因素。此外，携带TNF 308.2等位基因和/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（均为p = 0.0001）。总之，TNF308.2等位基因、物质使用习惯和慢性HBV/HCV感染对HCC的风险有独立和叠加的交互作用。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的高风险。
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)2 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.