Deng Yan, Li Meng, Wang Jian, Xie Li, Li Taijie, He Yu, Lu Qinghua, Li Ruolin, Tan Aihua, Qin Xue, Li Shan
Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.
Tumour Biol. 2014 Jul;35(7):6383-8. doi: 10.1007/s13277-014-1863-7. Epub 2014 Mar 26.
Hepatocellular carcinoma (HCC) is one of the most deadly malignant diseases in the world. Genetic variations in cytokine genes may have an effect on the immune and inflammatory responses which are associated with HBV-HCC. The interleukin-6 (IL-6) receptor is known to be mainly expressed by hepatocytes, neutrophils, monocytes/macrophages, and some lymphocytes, which have been used as prognostic markers in a variety of inflammatory diseases such as rheumatoid arthritis, asthma, and Crohn's disease. To determine the association of IL-6 receptor (IL-6R) polymorphism with the risk of hepatocellular carcinoma (HCC) development in the Chinese population, a hospital based case-control study was designed consisting of 192 subjects with HCC and 192 healthy control subjects. Our results revealed no risk associations (p = 0.064) with rs6684439 CT genotypes. However, rs6684439 TT genotypes were associated with a significantly decreased risk of HBV-related HCC compared with the CC genotype (odds ratio (OR) = 0.469, 95 % confidence interval (CI) 0.228-0.967, p = 0.040). The data also revealed that subjects with the T allele appeared to have a lower susceptibility to HBV-related HCC than those with the C allele (OR = 0.657, 95 % CI 0.476-0.907, p = 0.011). The present study supports the view that variants in the rs6684439 SNP of IL-6R is associated with a lower risk of HBV-related HCC, and this could provide valuable clues to understanding the mechanisms underlying susceptibility to this malignant disease. Replication and further functional studies should be carried out in the future using larger samples.
肝细胞癌(HCC)是世界上最致命的恶性疾病之一。细胞因子基因的遗传变异可能会影响与乙肝相关肝细胞癌有关的免疫和炎症反应。已知白细胞介素-6(IL-6)受体主要由肝细胞、中性粒细胞、单核细胞/巨噬细胞以及一些淋巴细胞表达,这些细胞已被用作类风湿性关节炎、哮喘和克罗恩病等多种炎症性疾病的预后标志物。为了确定IL-6受体(IL-6R)基因多态性与中国人群肝细胞癌(HCC)发生风险的关联,开展了一项基于医院的病例对照研究,该研究由192例HCC患者和192例健康对照者组成。我们的结果显示,rs6684439 CT基因型不存在风险关联(p = 0.064)。然而,与CC基因型相比,rs6684439 TT基因型与乙肝相关HCC风险显著降低相关(优势比(OR)= 0.469,95%置信区间(CI)0.228 - 0.967,p = 0.040)。数据还显示,携带T等位基因的受试者比携带C等位基因的受试者对乙肝相关HCC的易感性似乎更低(OR = 0.657,95% CI 0.476 - 0.907,p = 0.011)。本研究支持以下观点:IL-6R的rs6684439单核苷酸多态性(SNP)变异与乙肝相关HCC的较低风险相关,这可为理解这种恶性疾病易感性的潜在机制提供有价值的线索。未来应使用更大样本进行重复和进一步的功能研究。