Association between matrix metalloproteinase 2 (MMP2) promoter polymorphisms and the susceptibility to non-Hodgkin's lymphoma in Egyptians.

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases capable of extracellular matrix degradation. MMP2 is the key molecule that control invasion, tumor growth, and metastasis, and has been associated with poor prognosis in several tumors. Several epidemiological studies have focused on the associations between MMP2 promoter polymorphisms and cancer susceptibility; however, little is known about their role in hematological malignancies. The present study aimed to investigate the association of MMP2 -735C/T and -1306C/T promoter polymorphisms with B-NHL susceptibility and their clinicopathological characteristics. The study included 100 B-NHL patients and 100 healthy controls. Genotyping of MMP2 -735C/T and MMP2 -1306C/T was done by polymerase chain reaction restricted fragment length polymorphism (PCR-RFLP) technique. MMP2 -735C/T heteromutant genotype (CT) was detected in 23 % of patients, and the homomutant genotype (TT) was detected in 7 % of patients. The polymorphic allele, T allele, was associated with susceptibility to B-NHL (OR = 2.8:95 %CI = 1.48-5.28). For MMP2 -1306C/T, the frequencies of the polymorphic variants were 5 % for the heteromutant genotype (CT) and 3 % for the homomutant genotype (TT). The polymorphic allele, T allele, conferred almost fourfold increased risk of B-NHL (OR = 3.8, 95 %CI = 1.05-13.9), and the risk elevated to be almost eight folds when confined to diffuse large B-cell lymphoma (DLBCL) (OR = 7.9, 95 %CI = 1.67-32.27). MMP2 -735C/T polymorphic genotypes were correlated with advanced clinical stages of the disease (stages III and IV). In conclusion, the study revealed that the variant alleles of MMP2 -735C/T and MMP2 -1306C/T can be considered as molecular risk factors for B-NHL among Egyptians.

Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in chronic myeloid leukemia: an Egyptian study.

Methylenetetrahydrofolate reductase (MTHFR) gene plays a pivotal role in folate metabolism. Several genetic variations in MTHFR gene as MTHFR-C677T and MTHFR-A1298C result in decreased MTHFR activity, which could influence efficient DNA methylation and explain susceptibility to different cancers. The etiology of chronic myeloid leukemia (CML) is obscure and little is known about individual's susceptibility to CML. In order to assess the influence of these genetic polymorphisms on the susceptibility to CML and its effect on the course of the disease among Egyptians, we performed an age-gender-ethnic matched case-control study. The study included 97 CML patients and 130 healthy controls. Genotyping of MTHFR-C677T and -A1298C was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The results showed no statistical difference in the distribution of MTHFR-C677T and -A1298C polymorphic genotypes between CML patients and controls. The frequency of MTHFR 677-TT homozygous variant was significantly higher in patients with accelerated/blastic transformation phase when compared to those in the chronic phase of the disease. In conclusion, our study revealed that MTHFR-C677T and -A1298C polymorphisms could not be considered as genetic risk factors for CML in Egyptians. However, MTHFR 677-TT homozygous variant might be considered as a molecular predictor for disease progression.

Quantitative assessment of Wilms tumor 1 (WT1) gene transcripts in Egyptian acute lymphoblastic leukemia patients.

BACKGROUND: Accurate assessment of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) patients after initial chemotherapy is essential to evaluate the efficacy of therapeutic regimens. Wilms tumor 1 (WT1) is a pan-leukemic marker used for identification of the leukemic clone rather than the use of individual specific molecular aberration of ALL. METHODS: Using a real-time quantitative polymerase chain reaction, bone marrow samples from 41 newly diagnosed Egyptian ALL patients; 22 adults and 19 children were examined for WT1 expression. After induction therapy, WT1 expression was reestimated in 20 ALL patients. RESULTS: WT1 was overexpressed in adult and pediatric ALL patients (95.4% and 89.4%, respectively). WT1 expression at diagnosis had no statistically significant impact on disease-free survival of patients (P = 0.054). However, WT1 expression increased after induction chemotherapy in the 3 pediatric patients who had relapse. CONCLUSIONS: WT1 is a leukemia-associated molecular marker that may be used for the diagnosis and for monitoring clinical progress in ALL; it also can be used as a molecular target for adoptive immunotherapy.

A localized case-control study of extra-gastric manifestations of Helicobacter pylori infection in children.

OBJECTIVE: To study extra- gastric manifestations of H. pylori infection among children in Egypt. METHODS: This case-control study in which thirty [corrected] H pylori positive children were compared to thirty [corrected] H pylori negative children was conducted. Full history taking, clinical examination, CBC, serum iron, serum ferritin in addition to H pylori antibody testing were performed. RESULTS: Mean hemoglobin, MCV, MCH, serum iron and serum ferritin were all less in seropositive patients but these were statistically non significant. Iron deficiency (ID) was defined as serum ferritin less than 12 ng/ml; and Iron deficiency anemia (IDA) as hemoglobin less than 11 g/dL in addition to ID. Seropositive patients showed increased frequency of ID and IDA and this was statistically significant (0.003 & 0.000 respectively). There was no statistically significant difference as regards the platelet counts of the two groups or the presence of skin disorders or the gender. CONCLUSIONS: There is increased incidence of ID and IDA among H pylori positive children. This needs to be confirmed by larger therapeutic randomized controlled trials. The hematological response to eradication therapy needs to be further studied.