Yoon Young Joon, Chang Hye Young, Ahn Sang Hoon, Kim Ja Kyung, Park Yong Kwang, Kang Dae Ryong, Park Jun Yong, Myoung Sung Min, Kim Do Young, Chon Chae Yoon, Han Kwang-Hyub
Department of Internal Medicine, YonseiUniversity College of Medicine, Seoul 120-752, Korea.
Carcinogenesis. 2008 Jun;29(6):1192-6. doi: 10.1093/carcin/bgn090. Epub 2008 Apr 4.
A single-nucleotide polymorphism (SNP) in the promoter region of MDM2, SNP 309, is associated with hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus infection. The effect of p53 codon 72 polymorphism Arg72Pro on HCC risk remains inconsistent. This study evaluated the association of MDM2 and p53 polymorphisms with the presence and early onset of HCC in Korean patients with chronic hepatitis B virus (HBV) infection. In total, 583 consecutive patients with chronic HBV infection were classified according to the presence (n = 287) or absence (n = 296) of HCC. The MDM2 SNP 309 and p53 Arg72Pro were genotyped using restriction fragment length polymorphism method. The MDM2 G/G and p53 Pro/Pro genotypes were more frequent in HCC group than in non-HCC group (P < 0.001 and P = 0.004, respectively). Multivariate analysis for the presence of HCC revealed that the odds ratio (OR) for MDM2 G/G over T/T was 4.89 (P < 0.001) and that of p53 Pro/Pro over Arg/Arg was 3.03 (P = 0.006). Combined MDM2 G/G and p53 Pro/Pro had a synergistic effect on HCC risk, with an OR of 20.78 (P < 0.001). The mean age of tumor onset in patients with MDM2 G/G genotype was 50.9 years compared with 55.1 with T/T genotype (P = 0.018) and that with p53 Pro/Pro was 49.7 years compared with 52.9 with Arg/Arg (P = 0.040). Thus, MDM2 SNP 309 and p53 Arg72Pro are associated with the early development of HCC in Korean patients with chronic HBV infection.
MDM2启动子区域的单核苷酸多态性（SNP），即SNP 309，与慢性丙型肝炎病毒感染患者的肝细胞癌（HCC）相关。p53密码子72多态性Arg72Pro对HCC风险的影响仍不一致。本研究评估了MDM2和p53多态性与韩国慢性乙型肝炎病毒（HBV）感染患者HCC的存在及早期发病的相关性。总共583例连续的慢性HBV感染患者根据是否存在HCC分为两组（HCC组n = 287，非HCC组n = 296）。采用限制性片段长度多态性方法对MDM2 SNP 309和p53 Arg72Pro进行基因分型。MDM2 G/G和p53 Pro/Pro基因型在HCC组中比在非HCC组中更常见（分别为P < 0.001和P = 0.004）。对HCC存在情况的多变量分析显示，MDM2 G/G相对于T/T的优势比（OR）为4.89（P < 0.001），p53 Pro/Pro相对于Arg/Arg的OR为3.03（P = 0.006）。MDM2 G/G和p53 Pro/Pro联合对HCC风险有协同作用，OR为20.78（P < 0.001）。MDM2 G/G基因型患者肿瘤发病的平均年龄为50.9岁，而T/T基因型患者为55.1岁（P = 0.018），p53 Pro/Pro基因型患者为49.7岁，而Arg/Arg基因型患者为52.9岁（P = 0.040）。因此，MDM2 SNP 309和p53 Arg72Pro与韩国慢性HBV感染患者HCC的早期发生相关。
