Neoplasma. 2016;63(6):961-966. doi: 10.4149/neo_2016_615.
The transcriptional activity of transforming growth factor-β (TGF-β) is increased in subjects with hepatocellular carcinoma (HCC). Recent studies have indicated that the -509C genotype in hepatitis B virus (HBV)-infected subjects and the -509T genotype in hepatitis C virus (HCV)-infected subjects can increase the transcriptional activity of the TGF-β1 gene. We conducted a meta-analysis to clarify whether these two hepatitis viruses affect the association between TGF-β1 C-509T variants and HCC susceptibility. Using data derived from 8 case-control studies available in the PubMed database (5 with Asian and 3 with Caucasian populations), including 1,427 cases and 3,735 controls [1,610 patients with chronic liver disease and 2,125 healthy controls], we calculated pooled odds ratios with corresponding 95% confidence intervals. We used dominant (TT + CT vs. CC), recessive (TT vs. CC + CT), and co-dominant (TT vs. CC and CT vs. CC) genetic models. An overall analysis showed no association between the TGF-β1 C-509T variants and HCC susceptibility for all models. In contrast, a subgroup analysis, based on the infecting hepatitis viruses, provided the following results. Among the cases and controls with chronic liver disease, the TGF-β1 C-509T variants were significantly associated with decreased HCC susceptibility for two models with HBV-infected subjects, whereas the variants were significantly associated with increased HCC susceptibility for one model with HCV-infected subjects. Among the cases and healthy controls, there was a significant association between the TGF-β1 C-509T variants and increased HCC susceptibility for two models involving HCV-infected subjects. Among the cases and the entire control group, the same results were obtained for all genetic models with HCV-infected subjects. Although further data accumulation is required, our results suggest that these two hepatitis viruses affect the association between TGF-β1 C-509T variants and HCC susceptibility in opposite manners.
转化生长因子-β（TGF-β）的转录活性在肝细胞癌（HCC）患者中增加。最近的研究表明，乙型肝炎病毒（HBV）感染患者中的-509C 基因型和丙型肝炎病毒（HCV）感染患者中的-509T 基因型可以增加 TGF-β1 基因的转录活性。我们进行了一项荟萃分析，以阐明这两种肝炎病毒是否会影响 TGF-β1 C-509T 变体与 HCC 易感性之间的关联。利用来自 PubMed 数据库的 8 项病例对照研究的数据（5 项为亚洲人群，3 项为白种人群），包括 1427 例病例和 3735 例对照[1610 例慢性肝病患者和 2125 例健康对照]，我们计算了合并的优势比及其相应的 95%置信区间。我们使用了显性（TT+CT 与 CC）、隐性（TT 与 CC+CT）和共显性（TT 与 CC 和 CT 与 CC）遗传模型。总体分析显示，所有模型中 TGF-β1 C-509T 变体与 HCC 易感性之间均无关联。相反，基于感染的肝炎病毒的亚组分析提供了以下结果。在慢性肝病患者和对照组中，对于 HBV 感染患者的两个模型，TGF-β1 C-509T 变体与 HCC 易感性降低显著相关，而对于 HCV 感染患者的一个模型，变体与 HCC 易感性增加显著相关。在 HCV 感染患者的病例和健康对照组中，对于两个模型，TGF-β1 C-509T 变体与 HCC 易感性增加之间存在显著关联。在 HCV 感染患者的病例和整个对照组中，对于所有遗传模型，都得到了相同的结果。尽管需要进一步的数据积累，但我们的结果表明，这两种肝炎病毒以相反的方式影响 TGF-β1 C-509T 变体与 HCC 易感性之间的关联。
