Mdm2 SNP309 G-variant is associated with invasive growth of human urinary bladder cancer.
OBJECTIVE
Human mouse double minute 2 (Mdm2) is essential in degrading p53 by acting as an ubiquitin ligase and therefore plays a vital role in cell cycle and survival. The G-variant of the Mdm2 SNP309, which is located within the promoter of the Mdm2 gene, increases expression of Mdm2 and thereby inhibits the p53 pathway. Several studies have investigated the influence of this SNP on disease risk and onset of various malignancies. The impact of Mdm2 SNP309 on bladder cancer is still to be established due to inconsistent data.


METHODS
In a case-control study we determined the distribution of Mdm2 SNP309 genotypes in 111 patients with an early-onset bladder cancer (diagnosis <45 years of age), in 113 consecutive bladder cancer patients and in a control group consisting of 140 patients without any malignancy.


RESULTS
There was no significant association between the allelic distribution of the Mdm2 SNP309 and tumor risk, early onset, gender or grade of the tumor. According to tumor stage we found a significant difference in the distribution of the Mdm2 SNP309 between patients with noninvasive and invasive (≥pT1) tumor growth (p = 0.016). In patients with invasive tumors a significant increase of the G allele was found (T/T vs. T/G + G/G; p = 0.023; OR 2.203, 95% CI 1.111-4.369).


CONCLUSIONS
These data indicate that the G-variant of the Mdm2 SNP309 might influence the development of a more aggressive tumor phenotype in patients with bladder cancer without affecting the overall tumor risk.
Department of Internal Medicine I, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany.
Florian
F
Hitzenbichler
Christine G
CG
Stoehr
Michael
M
Rogenhofer
Wolf F
WF
Wieland
Petra
P
Ruemmele
Arndt
A
Hartmann
Robert
R
Stoehr
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2