p53基因第72密码子多态与中国人群肝细胞癌遗传易感性的研究

p53 gene codon 72 polymorphism and genetic susceptibility to hepatocellular carcinoma in Chinese population

目的探讨p53基因第72密码子多态(Arg72Pro)与中国人群肝细胞癌(HCC)遗传易感性的关系。方法采用聚合酶链反应限制性片段长度多态方法,检测507例HCC患者与541例对照组肝正常组织p53Arg72Pro基因型分布及差异。结果HCC组及对照组Pro等位基因频率分别为445%及403%,Pro型的HCC发病风险是Arg型的119倍(95%CI=100～141,P=0053)。与Arg/Arg纯合子相比,Arg/Pro杂合子的HCC风险增加至121倍(95%CI=082～178,P=0341),而Pro/Pro纯合子的HCC风险显著增加至179倍(95%CI=106～301,P=0029)。将Arg/Arg、Arg/Pro和Pro/Pro视为不同的等级,经趋势Armitage检验,存在等位基因剂量效应关系(P=0046)。结论Pro增加HCC发病风险,并呈等位基因剂量效应关系,表明Pro/Pro基因型是中国人的HCC遗传易感因素。

Objective To investigate the possible association between the p53 Arg72Pro polymorphism and susceptibility to hepatocellular carcinoma (HCC) in Chinese population. Methods Genomic DNA of the normal liver tissues was extracted from 507 patients with HCC confirmed by histopathological examination and 541 patients with benign liver diseases. PCR-based restriction fragment length polymorphism (RFLP) method was used to determine the p53 Arg72Pro genotypes. Odds ratios (ORs) for HCC and 95% confidence intervals (CIs) from unconditional logistic regression models were used to evaluate the relative risks. Potential HCC risk factors were included in the logistic regression models as covariates in the multivariate analyses on genotype and HCC risk.Results The frequencies for Pro and Arg alleles were 0.445 and 0.555 respectively in the HCC cases, and 0.403 and 0.597 respectively in the controls. The Pro allele was marginally significantly associated with the presence of HCC (P=0.053) and had an increased risk for HCC (OR=1.19, 95% CI=1.00-1.41) as compared to the Arg allele. Carriers of the Pro, or the “risk” allele, had a 1.33-fold increased risk (95% CI=0.92-1.92, P=0.133) of HCC compared to the Arg-only carriers. Compared to Arg/Arg homozygote, Arg/Pro heterozygote had a 1.21-fold increased risk (95% CI=0.82-1.78, P=0.341), whereas Pro/Pro homozygote had a 1.79-fold increased risk (95% CI=1.06-3.01, P=0.029) of HCC (Armitage′s trend test, P=0.046).Conclusion The Pro allele of p53 Arg72Pro is associated with the presence of HCC and Pro/Pro homozygote is potentially one of the risk genetic risk factorss for HCC in Chinese populationa.