MDM2 promoter polymorphism is associated with increased susceptibility to hepatocellular carcinoma in Turkish population.
BACKGROUND
The mouse double minute 2 (MDM2) gene represents one of the central nodes in the p53 pathway. A naturally occurring T/G single nucleotide polymorphism (SNP) in the intronic promoter of MDM2, SNP309 (rs2279744), was shown to influence MDM2 expression and p53 activity. SNP in the promoter region of MDM2 gene has recently been shown to be associated with accelerated tumor formation in both hereditary and sporadic cancers in humans. In this study, we aim to evaluate the association of SNP309 with the risk of hepatocellular carcinoma (HCC) development among Turkish population.


METHODS
MDM2 SNP309 polymorphism was investigated in 110 confirmed subjects with HCC and 110 cancer-free control subjects matched on age, gender, smoking and alcohol consumption by using a polymerase chain reaction-restriction fragment length polymorphism assay.


RESULTS
The allele frequencies of case subjects (T, 0.48; G, 0.52) were significantly different from those of control subjects (T, 0.65; G, 0.35) (p=0.003). The proportion of GG genotype of the SNP309 in patients with HCC (26%) was significantly higher than that in patients without HCC (14%). We observed that compared with the TT genotype, the genotypes containing G allele [TG (OR, 2.19; 95% CI, 1.18-4.07; p=0.013) or GG (OR, 3.63; 95% CI, 1.65-8.00; p=0.001)] were associated with significant increased susceptibility to HCC.


CONCLUSIONS
Our findings suggest that the MDM2 promoter SNP309 G allele is associated with presence of HCC in Turkish population.
Akkiz
Hikmet
H
Cukurova University Faculty of Medicine Department of Gastroenterology, 01330 Adana, Turkey.
Sümbül
Ahmet Taner
AT
Bayram
Süleyman
S
Bekar
Aynur
A
Akgöllü
Ersin
E
D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate; D014421:Turkey / Q000453:epidemiology
D004273:DNA, Neoplasm; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2