Qiu Moqin, Liu Yingchun, Yu Xiangyuan, Qin Linyuan, Bei Chunhua, Zeng Xiaoyun, Qiu Xiaoqiang, Tang Bo, He Songqing, Yu Hongping
Department of Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical College, 15 Le qun Road, Guilin, 541001, China.
Guangxi Zhuang Autonomous Region Center for Disease Control and Prevention, 18 Jin zhou Road, Nanning, 530028, China.
Tumour Biol. 2016 Mar;37(3):3863-70. doi: 10.1007/s13277-015-4222-4. Epub 2015 Oct 17.
The p53 tumor suppressor and its negative regulator, murine double minute 2 (MDM2), play critical roles in carcinogenesis. P53 codon 72 and MDM2 309T>G polymorphisms could influence p53 and MDM2 function, respectively, and might affect cancer susceptibility. We therefore investigated the association between these two SNPs, alone or in combination, and the risk of hepatocellular carcinoma (HCC) in Chinese. In this case-control study, we genotyped p53 codon 72 and MDM2 309T>G polymorphisms in 985 HCC cases and 992 cancer-free age- and sex-matched controls and evaluated their associations with the risk of HCC. Although no significant main effects were found for these two SNPs in the single-locus analysis and stratified analysis by age, sex, smoking, drinking, and hepatitis B virus (HBV) infection, we found that individuals carrying at least one G allele of the MDM2 309T>G polymorphism had statistically significant increased risk of HCC among those with the p53 Pro/Pro genotype (adjusted odds ratio (OR) = 2.23, 95 % confidence interval (95%CI) = 1.20-4.14 for TG genotype; adjusted OR = 2.67, 95%CI = 1.32-5.42 for GG genotype), and the interaction between p53 codon 72 and MDM2 309T>G was significant (P interaction = 0.017). Our findings suggest that the interaction of p53 codon 72 and MDM2 309T>G may play an important role in the etiology of HCC. More studies with well-designed and large sample sizes are required to validate these observations.
p53肿瘤抑制因子及其负调控因子小鼠双微体2（MDM2）在肿瘤发生过程中发挥着关键作用。p53第72位密码子和MDM2 309T>G多态性可能分别影响p53和MDM2的功能，并可能影响癌症易感性。因此，我们研究了这两个单核苷酸多态性（SNP）单独或联合与中国人群肝细胞癌（HCC）风险之间的关联。在这项病例对照研究中，我们对985例HCC患者和992例年龄及性别匹配的无癌对照进行了p53第72位密码子和MDM2 309T>G多态性基因分型，并评估了它们与HCC风险的关联。尽管在单基因座分析以及按年龄、性别、吸烟、饮酒和乙型肝炎病毒（HBV）感染进行的分层分析中，未发现这两个SNP有显著的主效应，但我们发现，在p53 Pro/Pro基因型个体中，携带MDM2 309T>G多态性至少一个G等位基因的个体患HCC的风险有统计学意义的增加（TG基因型调整优势比（OR）=2.23，95%置信区间（95%CI）=1.20 - 4.14；GG基因型调整OR = 2.67，95%CI = 1.32 - 5.42），并且p53第72位密码子和MDM2 309T>G之间的相互作用显著（P相互作用=0.017）。我们的研究结果表明，p53第72位密码子和MDM2 309T>G的相互作用可能在HCC的病因学中起重要作用。需要更多设计良好且样本量大的研究来验证这些观察结果。
