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Polymorphisms in key regulator genes of the intrinsic apoptosis pathway in risk and clinical presentation of diffuse large B‐cell lymphoma

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To the Editor Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for 30–40% of the newly diagnosed cases. Apoptosis is an important mechanism… Click to show full abstract

To the Editor Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for 30–40% of the newly diagnosed cases. Apoptosis is an important mechanism involved in lymphomagenesis, in which the pro-apoptotic B-cell lymphoma 2-associated X (Bax) and the anti-apoptotic Bcell lymphoma 2 (Bcl2) are the most active proteins [1]. It is already well established that the ability to induce apoptosis is variable in humans [2]. A single nucleotide polymorphism (SNP) located in the 5′-untranslated region of the BAX gene with a G→A substitution at 248 nucleotide position (rs4645878) has its allele ‘G’ associated with lower transcriptional activity when compared with ‘A’ allele [3]. Regarding BCL2 gene, a C→A substitution at 717 nucleotide position (rs2279115), located on the promoter region of the gene, has its AA genotype associated with increased Bcl2 expression in comparison with CC genotype [4]. Wang et al. [5] found excesses of the GA+AA genotype of BAX c. 248G>A and the AA genotype of BCL2 c.938C>A (rs2279115) SNPs in a mixed group of NHL patients compared to controls in China. The authors also found that the above mentioned genotypes were associated with dimension and stage of the tumour, respectively. Because DLBCL has a distinct behaviour in comparison with other types of NHL [6], and genetic variations in genes related to cellular homeostasis might have a crucial role in DLBCL development [7], the identification of BAX c. 248G>A and BCL2 c. 717C>A genotypes in patients with de novo DLBCL and controls was considered necessary to test whether SNPs influence the risk and clinical presentation of this aggressive NHL. The case group comprised 153 de novo DLBCL patients at diagnosis (median age: 56 years, range: 17–89 years, 70 males, 83 females, 140 Caucasians, 13 non-Caucasians), considering that 101 patients presented systemic symptoms seen at the Haematology and Haemotherapy Centre from December 2007 to June 2014. The diagnosis of DLBCL was established in accord with the World Health Organization criteria. R-IPI was calculated in each case as previously reported [8], and 16 patients were of very good R-IPI, 76 of good R-IPI, and 61 of poor R-IPI. The control group comprised 240 blood donors (median age: 49 years, range: 23–60 years, 124 males, 116 females,

Keywords: lymphoma; dlbcl; large cell; diffuse large; cell lymphoma

Journal Title: Hematological Oncology
Year Published: 2017

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