Increased risk of developing hepatocellular carcinoma associated with carriage of the TNF2 allele of the-308 tumor necrosis factor-α promoter gene

Increased risk of developing hepatocellular carcinoma associated with carriage of the TNF2 allele of the-308 tumor necrosis factor-α promoter gene
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DOI:
10.1023/b:caco.0000036173.99930.75
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发表时间:
2004-09-01
影响因子:
2.3
通讯作者:
Guo, HR
Guo, HR
中科院分区:
医学4区
文献类型:
--
作者:
Hol, SY;Wang, YJ;Guo, HR

文献摘要

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背景和目的:肿瘤坏死因子-α(TNF-α)是一种内源性肿瘤促进因子。在启动子区的位置-308处的TNF-α的遗传多态性,包括TNF 1(-308G)和TNF 2(-308A)等位基因,已被发现与对各种类型的癌症的易感性相关。方法:收集74例肝癌患者和289例健康对照者,采用聚合酶链反应-电泳技术检测TNF-α基因启动子-308位点基因型,并进行相关性分析(比值比[OR] = 3.5; 95%可信区间[CI]:[2.1,6.0]),从TNF 1/TNF 1、TNF 1/TNF 2到TNF 2/TNF 2基因型,观察到发生HCC的风险显著增加的趋势(p < 0.01)。在调整性别、年龄和B和C型肝炎标志物后,与TNF 2等位基因携带相关的HCC发生的OR为5.3(95%CI:[2.3,12.1]; p < 0.01)。结论:TNF 2等位基因携带是HCC的一个重要预测因子,与B和C型肝炎无关,因此它可以用作HCC易感性的生物标志物。
Background and Aims: Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that may act as an endogenous tumor promoter. A genetic polymorphism of TNF-alpha at position -308 of the promoter region, which includes TNF1 (-308G) and TNF2 (-308A) alleles, has been found to be associated with susceptibility to various types of cancer. We conducted a study to evaluate the association between this polymorphism and hepatocellular carcinoma (HCC).Methods: We recruited 74 HCC patients and 289 healthy controls, and determined their -308 TNF-alpha promoter genotypes through polymerase chain reaction followed by electrophoresis.Results: Carriage of the TNF2 allele was associated with an increased risk of HCC (odds ratio [OR] = 3.5; 95% confidence interval [CI]:[2.1, 6.0]), and a trend toward a significant increase in the risk of developing HCC was observed from TNF1/TNF1, TNF1/TNF2, to TNF2/TNF2 genotypes (p < 0.01). After adjustment for gender, age, and markers of hepatitis B and C, the OR of developing HCC associated with TNF2 allele carriage was 5.3 (95% CI: [2.3, 12.1]; p < 0.01).Conclusions: Carriage of the TNF2 allele is a significant predictor of HCC independent of hepatitis B and C, and therefore it may be used as a biomarker for susceptibility to HCC.