MDM2 SNP309 genotype is associated with ferritin and LDH serum levels in children with stage 4 neuroblastoma.
BACKGROUND
MDM2 SNP309, characterised by a T-to-G substitution in the MDM2 promoter, is associated with higher gene expression compared to wild type and was recently found to be a negative prognostic factor for patients with stage 4 neuroblastoma (NB), but not for children with localised disease. This polymorphism was not associated with any clinical or genetic tumour characteristics, including MYCN amplification and 1p chromosome deletion.


METHODS
To better define the involvement of MDM2 SNP309 in NB, we explored its association with the main biochemical tumour markers, namely urinary concentrations of vanillyl mandelic acid (VMA) and homovanillic acid (HVA) and blood concentrations of ferritin and lactate dehydrogenase (LDH). A cohort of 497 NB children, enrolled in the Italian Neuroblastoma Registry between January 1985 and December 2005 and previously investigated for the prognostic role of MDM2 SNP309, was considered for this study.


RESULTS
VMA and HVA concentrations as well as HVA/VMA ratio were not affected by the MDM2 SNP309 genotype. Ferritin and LDH concentrations were significantly lower in TT than in TG/GG only in patients with stage 4 disease (P = 0.007 and 0.015, respectively). No association emerged in patients with localised disease. These findings were not affected by confounding from clinical or biological characteristics.


CONCLUSIONS
The association between MDM2 SNP309 and both ferritin and LDH in patients with stage 4 disease confirms the prognostic role of this polymorphism. The results suggest that the MDM2 SNP309 genotype can impact on tumour responses to hypoxia and might play an important role in the alteration of energetic metabolism in NB cells.
Parodi
Stefano
S
Epidemiology and Biostatistics Section, Scientific Directorate, G. Gaslini Children's Hospital, Genova, Italy. stefanoparodi@ospedale-gaslini.ge.it
Perfumo
Chiara
C
Garaventa
Alberto
A
Inga
Alberto
A
Mazzocco
Katia
K
Defferrari
Raffaella
R
Tonini
Gian Paolo
GP
Fronza
Gilberto
G
Haupt
Riccardo
R
D014408:Biomarkers, Tumor / Q000097:blood / Q000652:urine; D002648:Child; D005293:Ferritins / Q000097:blood*; D005838:Genotype; D006801:Humans; D000860:Hypoxia; D045022:Lactate Dehydrogenases / Q000097:blood*; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*
D014408:Biomarkers, Tumor; D005293:Ferritins; D045022:Lactate Dehydrogenases; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2