Department of Occupational and Environmental Medicine, Sungseo Hospital, Daegu, South Korea.
Department of Preventive Medicine, School of Medicine and Institute for Cancer Research, Keimyung University, Daegu, South Korea.
Med Sci Monit. 2018 May 26;24:3488-3495. doi: 10.12659/MSM.907524.
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignancies occurring worldwide and is most frequent type of liver cancer. The risk for developing HCC increases with the severity of inflammation and fibrosis. The members of the interleukin-1 (IL-1) family are primarily proinflammatory cytokines due to their ability to stimulate the expression of genes associated with inflammation and autoimmune diseases. Several studies have suggested that some proinflammatory cytokines, such as the IL-1 family (IL-1α, IL-1β, and IL-1 receptor antagonist) are involved in the pathogenesis of HCC. MATERIAL AND METHODS This study aimed to determine whether polymorphisms in the IL-1 family of genes are associated with HCC. We analyzed 178 HCC patients and 397 controls to investigate the association between polymorphisms in IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1RA) genes and HCC in the Korean population. All subjects were genotyped for the selected SNPs in IL-1α, IL-1β, and IL-1RA genes by Golden-Gate SNP Genotyping Assay. RESULTS Statistical analysis revealed a significant association at IL-1β between HCC and controls. Three individual polymorphisms (rs1143633, rs3917356, and rs1143627) were found to be associated with HCC. The SNPs of IL-1b gene (rs1143633A>G and rs1143627T>C) protected against HCC in the dominant model (p=0.027, OR=0.59, 95% CI=0.37-0.94; p=0.019, OR=0.56, 95% CI=0.34-0.91). The SNP of IL-1β gene (rs3917356G>A) increased the risk of HCC in the recessive model (p<0.001, OR=2.58, 95% CI=1.53-4.33), whereas other SNPs in IL-1α and IL-1RA showed no significant association between HCC patients and controls. CONCLUSIONS These results suggest that IL-1β in the IL-1 family contributes to HCC susceptibility.
肝细胞癌（HCC）是全球最常见的恶性肿瘤之一，也是最常见的肝癌类型。发生 HCC 的风险随着炎症和纤维化的严重程度而增加。白细胞介素-1（IL-1）家族的成员主要是前炎性细胞因子，因为它们能够刺激与炎症和自身免疫性疾病相关的基因表达。一些研究表明，一些前炎性细胞因子，如 IL-1 家族（IL-1α、IL-1β 和 IL-1 受体拮抗剂）参与了 HCC 的发病机制。
本研究旨在确定白细胞介素-1 家族基因的多态性是否与 HCC 相关。我们分析了 178 例 HCC 患者和 397 例对照，以研究白细胞介素-1α、IL-1β 和白细胞介素-1 受体拮抗剂（IL-1RA）基因的多态性与韩国人群 HCC 之间的关系。所有受试者均通过 Golden-Gate SNP 基因分型检测对 IL-1α、IL-1β 和 IL-1RA 基因中的选定 SNP 进行了基因分型。
统计分析显示，IL-1β 与 HCC 和对照组之间存在显著关联。在 HCC 中发现三个个体多态性（rs1143633、rs3917356 和 rs1143627）与 HCC 相关。IL-1b 基因的 SNP（rs1143633A>G 和 rs1143627T>C）在显性模型中对 HCC 具有保护作用（p=0.027，OR=0.59，95%CI=0.37-0.94；p=0.019，OR=0.56，95%CI=0.34-0.91）。IL-1β 基因的 SNP（rs3917356G>A）在隐性模型中增加了 HCC 的风险（p<0.001，OR=2.58，95%CI=1.53-4.33），而 IL-1α 和 IL-1RA 中的其他 SNP 与 HCC 患者和对照组之间没有显著关联。
这些结果表明，IL-1 家族中的 IL-1β 有助于 HCC 的易感性。
