Abstract
BackgroundThe 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.MethodsEligible 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.ResultsFinally, 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.ConclusionsWe 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.
Highlights
Liver cancer, which consists predominantly of hepatocellular carcinoma (HCC), was the sixth most common cancer worldwide and the third most common cause of cancer mortality in 2008 [1]
A total of 10 studies including 2,243 cases and 3,615 controls were available for the meta-analysis of mouse double minute 2 (MDM2) SNP309 polymorphism and 14 studies containing 4,855 cases and 6,630 controls were included for TP53 R72P polymorphism
In subgroup analysis by hepatitis virus infection status, the results showed that the MDM2 SNP309 polymorphism was associated with increased HCC risk in hepatitis C virus (HCV) positive patients (G vs. T: odds ratio (OR) = 1.481, 95%confidence interval (CI): 1.245–1.761, P = 0.000; GG vs. TT: OR = 2.198, 95%CI: 1.542–3.134, P = 0.000; TG vs. TT: OR = 1.759, 95%CI: 1.280–2.418, P = 0.001; GG vs. TG+TT: OR = 1.507, 95%CI: 1.147–1.980, P = 0.003; GG+TG vs. TT: OR = 1.926, 95%CI: 1.426–2.601, P = 0.000) but not in hepatitis B virus (HBV) positive subjects
Summary
Liver cancer, which consists predominantly of hepatocellular carcinoma (HCC), was the sixth most common cancer worldwide and the third most common cause of cancer mortality in 2008 [1]. In high-risk China, liver cancer was the third most common cancer with 402,000 new cases and the second most common cause of death from cancer with 372,000 deaths in 2008 [2]. HCC is the fastest growing cause of cancer-related deaths in men of USA [3]. HCC accounts for about 90% of all primary liver cancers, and there are marked variations among geographic regions, racial, and ethnic groups, and between men and women [4]. 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
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