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The MDM 2 polymorphism SNP 309 is associated with clinical characteristics and outcome in diffuse large B‐cell lymphoma
Author(s) -
Hedström Gustav,
Thunberg Ulf,
Amini RoseMarie,
Zainuddin Norafiza,
Enblad Gunilla,
Berglund Mattias
Publication year - 2014
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12388
Subject(s) - lymphoma , rituximab , single nucleotide polymorphism , allele , hematology , snp , medicine , biology , immunology , immunotherapy , mdm2 , cancer research , gastroenterology , oncology , genotype , gene , genetics , cancer
The murine double minute 2 ( MDM 2) gene encodes a regulatory protein of the p53 pathway. A single nucleotide polymorphism (T to G change) at position 309 ( SNP 309) in the promotor region of MDM 2 affects the transcription activity of MDM 2 and has been found to be a negative prognostic marker in several cancers. Patients and methods In this study, the MDM 2 SNP 309 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 SNP 309T 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 aa IPI 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. Conclusion Polymorphism in MDM 2 SNP 309 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.