Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 140 Hanzhong Rd., Nanjing, 210029, China.
J Gastroenterol. 2013 Jan;48(1):125-31. doi: 10.1007/s00535-012-0620-1. Epub 2012 Jun 28.
The interleukin-23 receptor (IL-23R) plays an important role in the T-helper 17 cell-mediated inflammatory process and is also involved in tumor immune surveillance, which may be linked to carcinogenesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). In this study, we hypothesized that potentially functional genetic variants of the IL-23R gene may modify HCC risk.
We genotyped two single-nucleotide polymorphisms (SNPs) of IL-23R, rs6682925 and rs1884444, in a case-control study of 837 HCC cases, 899 HBV surface antigen (HBsAg)-positive controls, and 743 HBsAg-negative controls. A reporter gene assay was performed to evaluate the functional relevance of the rs6682925 SNP located at the promoter region of the IL-23R gene.
We found that the two SNPs were associated with the risk of HCC when compared with both the HBsAg-positive and -negative controls. When compared with all controls, IL-23R rs6682925 and rs1884444 both increased the HCC risk in a recessive genetic model [rs6682925 CC vs. TT/TC: odds ratio (OR) 1.35, 95 % confidence interval (CI) 1.07-1.70; rs1884444 GG vs. TT/TG: OR 1.36, 95 % CI 1.05-1.77]. Furthermore, the variant C allele of rs6682925 in the promoter region of IL-23R was associated with increased reporter gene activity.
These findings indicate that genetic variants in IL-23R may contribute to HCC development.
白细胞介素-23 受体 (IL-23R) 在 T 辅助 17 细胞介导的炎症过程中发挥重要作用，并且还参与肿瘤免疫监视，这可能与乙型肝炎病毒 (HBV) 相关的肝细胞癌 (HCC) 的发生有关。在这项研究中，我们假设 IL-23R 基因的潜在功能遗传变异可能会改变 HCC 的风险。
我们在一项病例对照研究中对 837 例 HCC 病例、899 例 HBV 表面抗原 (HBsAg) 阳性对照和 743 例 HBsAg 阴性对照进行了 IL-23R 基因的两个单核苷酸多态性 (SNP) rs6682925 和 rs1884444 的基因分型。我们进行了报告基因检测，以评估位于 IL-23R 基因启动子区域的 rs6682925SNP 的功能相关性。
我们发现，与 HBsAg 阳性和阴性对照相比，这两个 SNP 与 HCC 风险相关。与所有对照相比，IL-23R rs6682925 和 rs1884444 均以隐性遗传模式增加 HCC 风险[rs6682925 CC 与 TT/TC：比值比 (OR) 1.35，95%置信区间 (CI) 1.07-1.70；rs1884444 GG 与 TT/TG：OR 1.36，95% CI 1.05-1.77]。此外，IL-23R 启动子区域的 rs6682925 变体 C 等位基因与报告基因活性增加相关。
这些发现表明，IL-23R 中的遗传变异可能导致 HCC 的发生。
