Mdm2 Snp309 G allele displays high frequency and inverse correlation with somatic P53 mutations in hepatocellular carcinoma
Author
Acun T.
Terzioǧlu-Kara, E.
Konu, O.
Ozturk, M.
Yakicier, M. C.
Date
2010Source Title
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Print ISSN
1386-1964
Publisher
Elsevier
Volume
684
Issue
1-2
Pages
106 - 108
Language
English
Type
ArticleItem Usage Stats
147
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views
99
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Abstract
Loss of function of the p53 protein, which may occur through a range of molecular events, is critical in hepatocellular carcinoma (HCC) evolution. MDM2, an oncogene, acts as a major regulator of the p53 protein. A polymorphism in the MDM2 promoter, SNP309 (T/G), has been shown to alter protein expression and may thus play a role in carcinogenesis. MDM2 SNP309 is also associated with HCC. However, the role of SNP309 in hepatocarcinogenesis with respect to TP53 mutations is unknown. In this study, we investigated the distribution of the MDM2 SNP309 genotype and somatic TP53 (the p53 tumor suppressor gene) mutations in 99 human HCC samples from Africa, Europe, China and Japan. Samples exhibited striking geographical differences in their distribution of SNP309 genotypes. The frequency and spectrum of p53 mutations also varied geographically; TP53 mutations were frequent in Africa, where the SNP309 T/T genotype predominated but were rare in Europe and Japan, where the SNP309 G allele was present more frequently. TP53 mutations were detected in 18% (4/22) of SNP309 T/G and G/G and 82% (18/22) of SNP309 T/T genotype holders; this difference was statistically highly significant (P-value = 0.0006). Our results indicated that the presence of the SNP309 G allele is inversely associated with the presence of somatic TP53 mutations because they only coincided in 4% of HCC cases. This finding suggests that the SNP309 G allele may functionally replace p53 mutations, and in addition to known etiological factors, may be partly responsible for differential HCC prevalence. © 2009 Elsevier B.V. All rights reserved.
Keywords
Hepatocellular carcinomaMDM2 SNP309
Polymorphism
TP53
guanine
protein MDM2
protein p53
thymine
Africa
allele
article
China
controlled study
Europe
gene frequency
gene mutation
genetic association
genetic polymorphism
genetic variability
genotype
human
human cell
Japan
liver carcinogenesis
liver cell carcinoma
major clinical study
molecular mechanics
prevalence
priority journal
promoter region
protein expression
race difference
single nucleotide polymorphism
Alleles
Carcinoma, Hepatocellular
Gene Frequency
Genes, p53
Humans
Liver Neoplasms
Mutation
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins c-mdm2
Tumor Suppressor Protein p53
Permalink
http://hdl.handle.net/11693/22433Published Version (Please cite this version)
http://dx.doi.org/10.1016/j.mrfmmm.2009.11.008Collections
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