P53 codon72 and MDM2 SNP309 polymorphisms in hepatocellular carcinoma and comparison of them with tumor characteristics

Background and aims: The p53 tumor suppressor pathway plays an important role in cancer development. Murine double minute 2 (MDM2) gene is playing critical role in regulating tumor suppressor function of this pathway. A single nucleotide polymorphism (SNP) in the MDM2 in the intronic promoter, SNP309 was shown to be associated with both hereditary and sporadic cancers in humans. In addition, the wild-type p53 gene exhibits a polymorphism at codon 72 in exon 4, that causes a substitution of proline for arginine (Arg72Pro) and this substitution was shown to be related with different types of cancers in humans. In this study, we aim to determine the frequency and the association of MDM2 SNP309 and p53 Arg72Pro polymorphism in patients with hepatocellular carcinoma.Material and Methods: We conducted 128 control and 128 patients with hepatocellular carcinoma in our study. The MDM2 and p53 gene promoter region was amplified by polymerase chain reaction (PCR) and the SNP309 and Arg72Pro genotype determined by restriction enzyme digestion of the amplified DNA fragment. SPSS 15.0 (USA) statistic programme was used to determine the association between genotypes and hepatocellular carcinoma risk and charecteristics of tumors.Results: The MDM2 G/G and p53 Pro/Pro genotypes were more frequent in HCC group than in non-HCC group (p: 0.009 and p: 0.037, respectively). Logistic regrssion for the presence of HCC revealed that the odds ratio (OR) for MDM2 G/G over T/T was 2.76 (p: 0.036), and that of p53 Pro/Pro over Arg/Arg was 3.04 (p: 0.016). Combined, MDM2 G/G and p53 Pro/Pro had a synergistic effect on HCC risk, with an OR of 11.7 (p: 0.027).Conclusion: Our findings suggest that P53 codon72 Pro/Pro genotype and having G allel in MDM2 SNP309 position are potentially genetic risk factors for hepatocellular carcinoma in patients with chronic hepatitis and cirhosis. p53 codon72 Pro/Pro genotype and the G allele of MDM2 SNP309 could serve as an important genetic marker to identify a higher risk of hepatocellular carcinoma in patients with chronic hepatitis and cirhosis.