Abstract
BackgroundMDM2 gene polymorphisms 285G/C and 344 T/A are two single nucleotide polymorphisms (SNPs) recently identified as important variants that could influence the expression of MDM2 gene through the modulation of transcription factors binding on the SNP309T/G. The 285C variant seems to present a geographically distinct distribution in humans and to be associated with a low cancer risk. In the present report, we studied the distribution of the three SNPs in a population with low liver cancer incidence.MethodsA group of 119 patients with hepatocellular carcinoma (HCC, 63.45 ± 12.59 year, 26–80) and another of 103 non-HCC controls (56 ± 10.82 year, 22–79) were enrolled to investigate association between MDM2 polymorphisms and susceptibility to develop HCC. The three studied SNPs (285G/C, 309 T/G and 344 T/A) were genotyped using polymerase chain reaction and sequencing techniques.ResultsGenotypes and alleles distributions of the three studied polymorphisms of MDM2 were not significantly different between cases and controls. An increased risk of HCC development was found in case of 309G allele presence albeit without reaching the significance (29.8% vs 22.3%, OR = 1.48, 95% CI, 0.96-2.27, p = 0.073). In addition, neither 285C nor 344A MDM2 variants were significantly associated with an increased risk of HCC (p = 0.688 and p = 1 respectively). Remarkably, we found that the supposedly Caucasian-specific 285C variant was present in 1% of the Moroccan population.ConclusionsThis is the first study of the MDM2 SNP285G/C and SNP344T/A polymorphisms in association with HCC development. In contrast with previous studies, showing that females carrying SNP285C variant have a significantly reduced risk of developing breast, ovarian and endometrial cancer, no significant modulation of HCC risk was found in a North-African population.
Highlights
MDM2 gene polymorphisms 285G/C and 344 T/A are two single nucleotide polymorphisms (SNPs) recently identified as important variants that could influence the expression of MDM2 gene through the modulation of transcription factors binding on the SNP309T/G
It is well established that HCC results from a complex tumorigenic process that occurs on a background of genetic and epigenetic alterations where environment and lifestyle
Individual susceptibility to HCC has been already studied in various populations and germinal variants of several genes were earmarked as associated with susceptibility [13,14,15]
Summary
MDM2 gene polymorphisms 285G/C and 344 T/A are two single nucleotide polymorphisms (SNPs) recently identified as important variants that could influence the expression of MDM2 gene through the modulation of transcription factors binding on the SNP309T/G. Beside the TP53 gene and its Arg72Pro polymorphism, MDM2 gene, a negative regulator of the former with the SNP 309 T > G in the promoter region, is associated with hepatocellular carcinoma [16] This SNP was described for the first time by Bond et al (2004), to be associated with accelerated tumor formation, and studied in a multitude of cancers [17,18]. Seven different studies, including one survey on the Moroccan population, were evaluated [16] This meta-analysis confirms the predisposing effect of MDM2 309G variant to HCC [19]. Another polymorphism on MDM2, 344 T > A SNP was identified in 2004 as accelerating tumor formation [17]. A G > C SNP located 24 base pair upstream the 309G > T SNP was described concomitantly by Knappskog et al and Paulin et al This 285C variant was found to antagonize the binding effect of SNP309T on Sp1 transcription factor [20,21]
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