Su Shih-Chi, Hsieh Ming-Ju, Chou Ying-Erh, Fan Wen-Lang, Yeh Chao-Bin, Yang Shun-Fa
From the Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung (S-CS, W-LF); Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou (S-CS); Cancer Research Center, Changhua Christian Hospital, Changhua (M-JH); Institute of Medicine (M-JH, S-FY); Department of Forensic Medicine, Chung Shan Medical University (Y-EC); Department of Medical Research (Y-EC, S-FY); Department of Emergency Medicine, Chung Shan Medical University Hospital (C-BY); and Department of Emergency Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan (C-BY).
Medicine (Baltimore). 2015 Aug;94(34):e1396. doi: 10.1097/MD.0000000000001396.
Hepatocellular carcinoma (HCC) is a common malignancy of the liver, whose heterogeneous incidence reflects genetic variations among individuals in the main risk factors. The receptor for advanced glycosylation endproducts (RAGE) is a multiligand receptor and known to be implicated in various pathogenic conditions, such as diabetes, inflammatory disorder, Alzheimer disease, and cancer. In this study, the impact of RAGE gene polymorphisms on the susceptibility to hepatocarcinogenesis was explored. Four single-nucleotide polymorphisms (SNPs), rs184003 (1704G > T), rs1800624 (-374T > A), rs1800625 (-429T > C), and rs2070600 (Gly82Ser), as well as 1 gene polymorphism of RAGE gene, a 63 bp deletion allele (-407 to -345) were analyzed between 300 cancer-free subjects and 265 HCC cases. We detected a significant association of rs1800625 with the increased risk of HCC (odds ratio [OR], 2.565; 95% confidence interval [CI], 1.492-4.409 and adjusted odds ratio [AOR], 2.568; 95% CI, 1.418-4.653). However, patients who possess at least 1 polymorphic allele of rs1800625 are less prone to develop late-stage (stage III/IV, OR, 0.502; 95% CI, 0.243-1.037; P = 0.059 and AOR, 0.461; 95% CI, 0.219-0.970; P = 0.041) and large-size tumors (OR, 0.398; 95% CI, 0.183-0.864; P = 0.017 and AOR, 0.351; 95% CI, 0.157-0.781; P = 0.010). Furthermore, individuals bearing specific haplotypes of 4 RAGE SNPs tested are more inclined to have HCC. In conclusion, our data suggest a correlation of RAGE gene polymorphism rs1800625 with the early stage of liver tumorigenesis and implicate its protective role in the progression of HCC.
肝细胞癌（HCC）是一种常见的肝脏恶性肿瘤，其发病率的异质性反映了主要风险因素中个体间的基因差异。晚期糖基化终产物受体（RAGE）是一种多配体受体，已知与多种致病情况有关，如糖尿病、炎症性疾病、阿尔茨海默病和癌症。在本研究中，探讨了RAGE基因多态性对肝癌发生易感性的影响。在300名无癌受试者和265例HCC病例之间分析了4个单核苷酸多态性（SNP），即rs184003（1704G>T）、rs1800624（-374T>A）、rs1800625（-429T>C）和rs2070600（Gly82Ser），以及RAGE基因的1个基因多态性，即63bp缺失等位基因（-407至-345）。我们检测到rs1800625与HCC风险增加显著相关（优势比[OR]，2.565；95%置信区间[CI]，1.492-4.409；调整后优势比[AOR]，2.568；9开5%CI，1.418-4.653）。然而，至少拥有1个rs1800625多态性等位基因的患者发生晚期（III/IV期，OR，0.502；95%CI，0.243-1.037；P=0.059；AOR，0.461；95%CI，0.219-0.970；P=0.041）和大尺寸肿瘤（OR，0.398；95%CI，0.183-0.864；P=0.017；AOR，0.351；95%CI，0.157-0.781；P=0.010）的倾向较小。此外，携带所检测的4个RAGE SNP特定单倍型的个体更易患HCC。总之，我们的数据表明RAGE基因多态性rs1800625与肝肿瘤发生的早期阶段相关，并暗示其在HCC进展中的保护作用。
