Peng Qiliu, Lao Xianjun, Chen Zhiping, Lai Hao, Deng Yan, Wang Jian, Mo Cuiju, Sui Jingzhe, Wu Junrong, Zhai Limin, Yang Shi, Qin Xue, Li Shan
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Department of Occupational Health and Environmental Health, School of Public Health at Guangxi Medical University, Nanning, Guangxi, China.
PLoS One. 2013 Dec 23;8(12):e82773. doi: 10.1371/journal.pone.0082773. eCollection 2013.
The association between TP53 R72P and/or MDM2 SNP309 polymorphisms and hepatocellular carcinoma (HCC) risk has been widely reported, but results were inconsistent. To clarify the effects of these polymorphisms on HCC risk, an updated meta-analysis of all available studies was conducted.
Eligible articles were identified by search of databases including PubMed, Cochrane Library, EMBASE and Chinese Biomedical Literature database (CBM) for the period up to July 2013. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity.
Finally, a total of 10 studies including 2,243 cases and 3,615 controls were available for MDM2 SNP309 polymorphism and 14 studies containing 4,855 cases and 6,630 controls were included for TP53 R72P polymorphism. With respect to MDM2 SNP309 polymorphism, significantly increased HCC risk was found in the overall population. In subgroup analysis by ethnicity and hepatitis virus infection status, significantly increased HCC risk was found in Asians, Caucasians, Africans, and HCV positive patients. With respect to TP53 R72P polymorphism, no significant association with HCC risk was observed in the overall and subgroup analyses. In the MDM2 SNP309-TP53 R72P interaction analysis, we found that subjects with MDM2 309TT and TP53 Pro/Pro genotype, MDM2 309 TG and TP53 Arg/Pro genotype, and MDM2 309 GG and TP53 Pro/Pro genotype were associated with significantly increased risk of developing HCC as compared with the reference MDM2 309TT and TP53 Arg/Arg genotype.
We concluded that MDM2 SNP309 polymorphism may play an important role in the carcinogenesis of HCC. In addition, our findings further suggest that the combination of MDM2 SNP 309 and TP53 Arg72Pro genotypes confers higher risk to develop HCC. Further large and well-designed studies are needed to confirm this association.
TP53基因R72P位点和/或MDM2基因SNP309位点多态性与肝细胞癌（HCC）风险之间的关联已被广泛报道，但结果并不一致。为阐明这些多态性对HCC风险的影响，我们对所有可用研究进行了一项更新的荟萃分析。
通过检索包括PubMed、Cochrane图书馆、EMBASE和中国生物医学文献数据库（CBM）在内的数据库，确定截至2013年7月的符合条件的文章。由两名独立作者提取数据，并计算合并比值比（OR）及95%置信区间（CI）。进行Meta回归和亚组分析以确定异质性来源。
最后，共有10项研究（包括2243例病例和3615例对照）可用于MDM2基因SNP309多态性分析，14项研究（包括4855例病例和6630例对照）纳入TP53基因R72P多态性分析。关于MDM2基因SNP309多态性，在总体人群中发现HCC风险显著增加。在按种族和肝炎病毒感染状态进行的亚组分析中，亚洲人、高加索人、非洲人和丙型肝炎病毒（HCV）阳性患者的HCC风险显著增加。关于TP53基因R72P多态性，在总体和亚组分析中均未观察到与HCC风险有显著关联。在MDM2基因SNP309 - TP53基因R72P相互作用分析中，我们发现与参考的MDM2基因309TT和TP53基因Arg/Arg基因型相比，MDM2基因309TT和TP53基因Pro/Pro基因型、MDM2基因309TG和TP53基因Arg/Pro基因型以及MDM2基因309GG和TP53基因Pro/Pro基因型的受试者发生HCC的风险显著增加。
我们得出结论，MDM2基因SNP309多态性可能在HCC的致癌过程中起重要作用。此外，我们的研究结果进一步表明，MDM2基因SNP309和TP53基因Arg72Pro基因型的组合使发生HCC的风险更高。需要进一步开展大规模、设计良好的研究来证实这种关联。
