MDM2 gene SNP309 T/G and p53 gene SNP72 G/C do not influence diffuse large B-cell non-Hodgkin lymphoma onset or survival in central European Caucasians.
BACKGROUND
SNP309 T/G (rs2279744) causes higher levels of MDM2, the most important negative regulator of the p53 tumor suppressor. SNP72 G/C (rs1042522) gives rise to a p53 protein with a greatly reduced capacity to induce apoptosis. Both polymorphisms have been implicated in cancer. The SNP309 G-allele has recently been reported to accelerate diffuse large B-cell lymphoma (DLBCL) formation in pre-menopausal women and suggested to constitute a genetic basis for estrogen affecting human tumorigenesis. Here we asked whether SNP309 and SNP72 are associated with DLBCL in women and are correlated with age of onset, diagnosis, or patient's survival.


METHODS
SNP309 and SNP72 were PCR-genotyped in a case-control study that included 512 controls and 311 patients diagnosed with aggressive NHL. Of these, 205 were diagnosed with DLBCL.


RESULTS
The age of onset was similar in men and women. The control and patients group showed similar SNP309 and SNP72 genotype frequencies. Importantly and in contrast to the previous findings, similar genotype frequencies were observed in female patients diagnosed by 51 years of age and those diagnosed later. Specifically, 3/20 female DLBCL patients diagnosed by 51 years of age were homozygous for SNP309 G and 2/20 DLBCL females in that age group were homozygous for SNP72 C. Neither SNP309 nor SNP72 had a significant influence on event-free and overall survival in multivariate analyses.


CONCLUSIONS
In contrast to the previous study on Ashkenazi Jewish Caucasians, DLBCL in pre-menopausal women of central European Caucasian ethnicity was not associated with SNP309 G. Neither SNP309 nor SNP72 seem to be correlated with age of onset, diagnosis, or survival of patients.
Bittenbring
Joerg
J
Internal Medicine I and Josè Carreras Research Center, University of Saarland Medical School, Homburg-Saar, Germany. injbit@uniklinikum-saarland.de
Parisot
Frédérique
F
Wabo
Alain
A
Mueller
Monika
M
Kerschenmeyer
Lynn
L
Kreuz
Markus
M
Truemper
Lorenz
L
Landt
Olfert
O
Menzel
Alain
A
Pfreundschuh
Michael
M
Roemer
Klaus
K
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D016022:Case-Control Studies; D004252:DNA Mutational Analysis / Q000379:methods; D015342:DNA Probes; D005260:Female; D016158:Genes, p53; D005858:Germany / Q000208:ethnology; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D016019:Survival Analysis; D044465:White People / Q000235:genetics*
D015342:DNA Probes; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2