MDM2 SNP309 promoter polymorphism, an independent prognostic factor in chronic lymphocytic leukemia.
BACKGROUND
The single nucleotide polymorphism SNP309 with a change from T to G in the promoter region of the MDM2 gene is shown to increase the MDM2 protein levels and attenuate the p53 levels and associates with disease progression in several tumors.


OBJECTIVE
In this study, the role of the polymorphism was investigated with regard to the clinical outcome in B-cell chronic lymphocytic leukemia (B-CLL).


METHODS
A total of 210 patients with B-CLL were followed for up to 19 yr.


RESULTS
The overall survival (OS) of patients with at least one G-allele was significantly shorter when compared with those with two T-alleles (P = 0.024) with a more pronounced difference in patients below the median age. Age at onset of B-CLL was similar irrespective of MDM2 status. The presence of a G-allele in combination with TP53 mutations or unmutated IgVH gene status resulted in an additive risk of death.


CONCLUSIONS
In this report, with a high proportion of B-CLL patients with an advanced Binet stage and with an unmutated IgVH gene, MDM2 SNP309 was found to be independently associated with OS. The survival difference was more pronounced in younger patients.
Willander
Kerstin
K
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Ungerbäck
Jonas
J
Karlsson
Karin
K
Fredrikson
Mats
M
Söderkvist
Peter
P
Linderholm
Mats
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D007143:Immunoglobulin Heavy Chains; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2