MDM2 SNP309T>G polymorphism and risk of hepatocellular carcinoma: a case-control analysis in a Moroccan population.
BACKGROUND
The Murine double minute 2 (MDM2) gene encodes a negative regulator of the p53 tumor suppressor protein. A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been reported to produce accelerated tumor formation. The aim of this study was to investigate whether this functional SNP is associated with an enhanced risk of liver tumorigenesis in Moroccan patients.


METHODS
The study consisted in the comparison of 96 hepatocellular carcinomas (HCC) cases and 222 controls without HCC matched for age, gender and ethnicity. PCR-RFLP and sequencing methods were used to determine the genotype at the MDM2 SNP309T>G locus.


RESULTS
Overall, our results indicate that the GG genotype of SNP309 is significantly associated with an increased risk of HCC (odds ratio, OR=2.60, 95% CI, 1.08-6.28). Interestingly, despite a wide range of confidence interval, there is a trend associating the GG genotype with a high risk of HCC in males (OR=3.31; 95% CI, 0.93-11.82) and in HCV-infected patients (OR=3.7; 95% CI, 0.82-16.45). By contrast, no association between age at diagnosis and MDM2 SNP309 genotypes was observed in HCC patients (P=0.610).


CONCLUSIONS
Our findings suggest that the MDM2 309T>G polymorphism is an important modulator of hepatocellular carcinoma development in Moroccan patients.
Ezzikouri
Sayeh
S
Laboratoire de Virologie, Institut Pasteur du Maroc, Casablanca, Morocco. sayeh.ezzikouri@pasteur.ma
El Feydi
Abdellah Essaid
AE
Afifi
Rajae
R
El Kihal
Latifa
L
Benazzouz
Mustapha
M
Hassar
Mohammed
M
Marchio
Agnès
A
Pineau
Pascal
P
Benjelloun
Soumaya
S
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006525:Hepatitis, Viral, Human; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009018:Morocco / Q000453:epidemiology; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D012737:Sex Factors
C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2