title: The MDM2 polymorphism SNP309 is associated with clinical characteristics and outcome in diffuse large B-cell lymphoma.
abstract: BACKGROUND
  The murine double minute 2 (MDM2) gene encodes a regulatory protein of the p53 pathway. A single nucleotide polymorphism (T to G change) at position 309 (SNP309) in the promotor region of MDM2 affects the transcription activity of MDM2 and has been found to be a negative prognostic marker in several cancers.
  
  
  METHODS
  In this study, the MDM2 SNP309 polymorphism was analysed in 201 patients with diffuse large B-cell lymphoma and analysed in relation to clinical characteristics and prognosis.
  
  
  RESULTS
  Patients homozygous for SNP309T had a significantly longer overall survival, lymphoma-specific survival and disease-free survival (P = 0.002; 0.004 and 0.006 respectively) compared to patients carrying a G allele. The longer overall survival was seen in the subgroup of patients not treated with Rituximab, however, not for Rituximab-treated patients (P = 0.01 and 0.2 respectively). The group homozygous for the T allele also had lower age at diagnosis, a tendency towards lower aaIPI and a significantly lower proportion of patients with p53 aberrations compared to the group including at least one G allele. However, the survival differences persisted even after removal of cases with known p53 aberrations from the analysis.
  
  
  CONCLUSIONS
  Polymorphism in MDM2 SNP309 could be correlated to some clinical characteristics and for patients not treated with immunotherapy, a G allele was correlated to poor survival, whereas no survival differences were found for patients treated with Rituximab. Herewith, we provide additional information about Diffuse large B-cell Lymphoma (DLBCL) biology and highlight the importance of evaluation of molecular markers in relation to treatment.
authors.affiliation: Department of Radiology, Oncology and Radiation Sciences, Section of Oncology, Uppsala University, Uppsala, Sweden.
authors.forename: Gustav
authors.initials: G
authors.lastname: Hedström
authors.forename: Ulf
authors.initials: U
authors.lastname: Thunberg
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Amini
authors.forename: Norafiza
authors.initials: N
authors.lastname: Zainuddin
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
authors.forename: Mattias
authors.initials: M
authors.lastname: Berglund
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D055815:Young Adult
chemical_list: D051736:Proto-Oncogene Proteins c-mdm2
keywords: diffuse large B-cell lymphoma; murine double minute 2; prognostic; survival