The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Protein Cell. 2013 Jan;4(1):71-81. doi: 10.1007/s13238-012-2067-9. Epub 2012 Dec 22.
The p53 signaling pathway works as a potent barrier to tumor progression. Two single nucleotide polymorphisms (SNPs) in the gene loci of p53 pathway, p53 codon 72 Arg72Pro and MDM2 SNP309 (T > G), have been shown to cause perturbation of p53 function, but the effect of the two SNPs on the risk of hepatocellular carcinoma (HCC) remains inconsistent. This study investigated the influence of combined p53 Arg72Pro and MDM2 SNP309 on the risk of developing HCC in patients with chronic hepatitis B virus infection, and evaluated the significance of the two combined SNPs on patient prognosis. In total, 350 HCC patients, 230 non-HCC patients, and 96 healthy controls were genotyped for the p53 Arg72Pro and MDM2 SNP309. The combined p53 Pro/Pro and MDM2 G/G genotype was significantly associated with HCC risk (P = 0.047). Multivariate analysis indicated that combined p53 Pro/Pro and MDM2 G/G genotype was an independent factor affecting recurrence and survival (P < 0.05). Patients with combined p53 Pro/Pro and MDM2 G/G genotypes had a poorer prognosis than other genotypes, P < 0.01 for both disease-free survival (DFS) and overall survival (OS). DFS and OS rates also differed significantly between Barcelona Clinic Liver Cancer (BCLC) stage A patients with combined p53 Pro/Pro and MDM2 G/G and other genotypes (P < 0.05). Thus, the combined p53 Pro/Pro and MDM2 G/G genotype is associated with increased risk of developing HCC and is an independent adverse prognostic indicator in early stage HCC.
p53 信号通路作为肿瘤进展的强大障碍。p53 通路基因座中的两个单核苷酸多态性 (SNP)，即 p53 密码子 72 位精氨酸 72 脯氨酸 (Arg72Pro) 和 MDM2 SNP309（T>G），已被证明会导致 p53 功能紊乱，但这两个 SNP 对肝细胞癌 (HCC) 风险的影响仍不一致。本研究探讨了联合 p53 Arg72Pro 和 MDM2 SNP309 对慢性乙型肝炎病毒感染患者发生 HCC 的风险的影响，并评估了这两个联合 SNP 对患者预后的意义。共对 350 例 HCC 患者、230 例非 HCC 患者和 96 例健康对照者进行了 p53 Arg72Pro 和 MDM2 SNP309 的基因分型。p53 Pro/Pro 和 MDM2 G/G 基因型的联合与 HCC 风险显著相关 (P = 0.047)。多变量分析表明，联合 p53 Pro/Pro 和 MDM2 G/G 基因型是影响复发和生存的独立因素 (P < 0.05)。具有联合 p53 Pro/Pro 和 MDM2 G/G 基因型的患者预后较差，无病生存率 (DFS) 和总生存率 (OS) 均 P < 0.01。巴塞罗那临床肝癌 (BCLC) 分期 A 患者中，具有联合 p53 Pro/Pro 和 MDM2 G/G 基因型与其他基因型的患者之间 DFS 和 OS 差异也有统计学意义 (P < 0.05)。因此，联合 p53 Pro/Pro 和 MDM2 G/G 基因型与 HCC 发生风险增加相关，并且是早期 HCC 的独立不良预后指标。
