MDM2 gene SNP309 T/G and p53gene SNP72 G/C do not influence diffuse large B-cell non-Hodgkin lymphoma onset or survival in central European Caucasians

Abstract

BackgroundSNP309 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.MethodsSNP309 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.ResultsThe 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.ConclusionIn 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.

Diffuse large B-cell lymphoma with combinedTP53mutation andMIR34Amethylation: Another “double hit” lymphoma with very poor outcome?

“…However, in both studies only a limited amount of cases are investigated and none of them address the prognostic impact of MIR34A methylation. For the MDM2 SNP309 our observations are in line with previous studies [44, 45], which also show that the outcome in DLBCL is independent of the GG-phenotype.…”

MDM2 phenotypic and genotypic profiling, respective to TP53 genetic status, in diffuse large B-cell lymphoma patients treated with rituximab-CHOP immunochemotherapy: a report from the International DLBCL Rituximab-CHOP Consortium Program

“…Similarly, increased MDM2 expression was not shown in the homozygous (G/G) or heterozygous (G/T) for SNP309 tumor cells among 108 patients in this study, and SNP309 T→G did not correlate with significantly poorer survival. Although similar results have been shown in other reports, 48,49 the lack of significance may be attributable to a small number of patients, similar estrogen levels in the SNP309 groups, oscillation of MDM2 pulses, and the possibility that an endogenous MDM2 level could not be distinguished by IHC (which scores a fraction of positive cells but not the intensity).…”

Single-nucleotide Polymorphisms in the p53 Signaling Pathway

“…This was shown to result in the enrichment of individuals with the G-allele in premenopausal women with these cancers, when compared with either postmenopausal women or men with the same cancers. Subsequently, similar trends have been observed in melanoma and osteosarcoma patients (Firoz et al 2009;Toffoli et al 2009), whereas other studies suggest these trends will not be seen in every cancer and could be restricted to specific racial and ethnic backgrounds Bittenbring et al 2008;). …”