Signal transducer and activator of transcription 4 (STAT4) is closely related to liver diseases and affects the processes of inflammation and carcinogenesis by regulating immune responses. A single-nucleotide polymorphism rs7574865 (T > G) in STAT4 has been reported to be associated with the risk of hepatocellular carcinoma (HCC). In addition, hepatitis B virus (HBV) mutations are crucial risk factors for HBV-induced HCC. However, the effects of the interactions of STAT4 rs7574865 with HBV mutations on the risk of HCC remain unknown. Rs7574865 was genotyped in 846 healthy controls (HCs), 968 chronic hepatitis B (CHB) subjects, 316 liver cirrhosis (LC) subjects and 1021 HCC subjects using Sequenom MassArray. HBV mutations were detected via direct sequencing. Multivariate logistic regression analysis was used to evaluate the effects of the interactions of STAT4 rs7574865 with HBV mutations on the risk of HCC. We found that the rs7574865 TT genotype was significantly associated with HBeAg seroconversion (TT vs. GG, p = 0.012; TT vs. GT, p = 0.033). The rs7574865 GG genotype was significantly associated with increased risks of CHB (p = 0.048), LC (p = 0.005) and HCC (p < 0.001). The interaction term between rs7574865 and HBV C1913A significantly increased the risk of progression from CHB to HCC (p = 0.038), while the interaction term between rs7574865 and HBV T1674C significantly increased the risk of progression from LC to HCC (p = 0.023). STAT4 rs7574865 is significantly associated with the risks of CHB, LC and HCC. The interactions of rs7574865 with HBV C1913A and T1674C mutations significantly increase the risk of HCC, which have the potential to identify HBV-infected individuals who tend to progress from CHB or LC to HCC.

中文翻译：

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STAT4 rs7574865与HBV突变相互作用对肝细胞癌风险的影响

信号转导和转录激活因子4（STAT4）与肝脏疾病密切相关，通过调节免疫反应影响炎症和癌变过程。据报道， STAT4中的单核苷酸多态性 rs7574865 (T > G)与肝细胞癌 (HCC) 的风险相关。此外，乙型肝炎病毒 (HBV) 突变是 HBV 诱发的 HCC 的关键危险因素。然而， STAT4相互作用的影响具有HBV突变的rs7574865对HCC风险的影响仍然未知。使用 Sequenom MassArray 在 846 名健康对照 (HC)、968 名慢性乙型肝炎 (CHB) 受试者、316 名肝硬化 (LC) 受试者和 1021 名 HCC 受试者中对 Rs7574865 进行了基因分型。通过直接测序检测HBV突变。多变量逻辑回归分析用于评估STAT4 rs7574865 与 HBV 突变的相互作用对 HCC 风险的影响。我们发现 rs7574865 TT 基因型与 HBeAg 血清转换显着相关（TT 与 GG，p  = 0.012；TT 与 GT，p  = 0.033）。rs7574865 GG 基因型与 CHB ( p  = 0.048)、LC ( p  = 0.005) 和 HCC (p  < 0.001)。rs7574865 和 HBV C1913A 之间的相互作用项显着增加了从 CHB 进展为 HCC 的风险（p  = 0.038），而 rs7574865 和 HBV T1674C 之间的相互作用项显着增加了从 LC 进展为 HCC 的风险（p  = 0.023）。 STAT4 rs7574865 与 CHB、LC 和 HCC 的风险显着相关。rs7574865 与 HBV C1913A 和 T1674C 突变的相互作用显着增加了 HCC 的风险，这有可能识别出倾向于从 CHB 或 LC 发展为 HCC 的 HBV 感染个体。