p53基因Arg72Pro单核苷酸多态性与山东人群乙型肝炎相关肝细胞癌高发风险研究

目的 探讨在慢性乙型肝炎背景下，p53基因第72位密码子（Arg72Pro）多态性与山东汉族人群肝细胞癌（hepatocellular carcinoma，HCC）遗传易感性的关系。方法 采用TaqMan实时荧光定量PCR方法检测280例乙型肝炎相关肝细胞癌患者、280例慢性乙型肝炎患者以及310例健康人群的外周血标本p53基因Arg72Pro的多态性，并比较其不同的基因型与肝细胞癌发生风险的关系。结果 肝细胞癌组、慢性乙型肝炎组及健康对照组的Pro等位基因频率分别为0.525、0.393和0.376，HBV感染者中Pro/Pro基因型携带者的肝细胞癌发病风险是Arg/Arg基因型携带者的3.210倍[95% CI（1.959～5.232），P＜0.001]。肝癌患者中Pro/Pro基因型患者初次诊断为HCC的平均年龄显著低于Arg/Arg基因型（P=0.042）。结论 p53 Arg72Pro多态性与山东人群肝细胞癌遗传易感性相关，值得进一步进行功能学及相关机制探讨。

Effects of p53 gene codon 72 Arg/Pro polymorphisms on susceptibility of hepatocellular carcinoma in patients with hepatitis B virus infection in Shandong Province

Objective To investigate the influence of p53 codon 72 polymorphism on the risk of developing hepatocellular carcinoma (HCC) with chronic hepatitis B virus infection of Shandong Chinese population. Methods The Arg/Pro polymorphism of p53 gene were genotyped in 560 Shandong Chinese patients with chronic hepatitis B virus infection including 280 patients with hepatocellular carcinoma, and 310 healthy subjects. TaqMan SNP Genotyping Assays (Applied Biosystems) was applied. An association between genotypes and risk of HCC development was assessed. Results The Pro allele frequencies of p53 gene in patients with HCC (0.525) were significantly higher than those without HCC (0.393) and healthy controls (0.376). The Pro genotype had a more than 3.210 fold increased risk of HCC [OR=3.210; 95% CI (1.959 ~5.232), P<0.001]. The mean age of tumor onset in HCC patients with Pro/Pro was significantly lower than that in the Arg/Arg genotype (P=0.042). Conclusion p53 Arg72Pro is associated with the development of HCC in Shandong Chinese patients with chronic HBV infection, its function and related mechanism need to be further investigated.