Publications by authors named "Eman R Radwan"

3 Publications

  • Page 1 of 1

Variability of contribution of vitamin D receptor gene polymorphisms to outcome of HLA-matched sibling allogeneic bone marrow transplantation.

Leuk Lymphoma 2018 12 4;59(12):2963-2972. Epub 2018 Jul 4.

d Medical Oncology Department , NCI, Cairo University , Cairo , Egypt.

Graft-versus-host disease (GVHD) remains one of the major complications of hematopoietic stem cell transplantation (HSCT). Several etiological factors were investigated. Among these, vitamin D and hence its receptor (VDR) gene polymorphisms have gained much interest; however, the results are still controversial. Using PCR-RFLP, we genotyped VDR polymorphisms FokI (rs10735810), ApaI (rs7975232), and Taq1 (rs731236) in 80 patient/donor pairs according to DNA availability. No association was encountered between VDR polymorphisms and GVHD. Neither was there any impact on survival. Only grade II-IV acute GVHD was associated with inferior overall (p = .01), but not disease-free survival. The controversy between our results and the literature may be attributed to marked variability in the relative distribution of VDR genotypes in different populations. Also different environmental factors, including exposure to sun, may ensure vitamin D sufficiency nullifying the impact of VDR polymorphisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2018.1459608DOI Listing
December 2018

The impact of cytokine gene polymorphisms on the outcome of HLA matched sibling hematopoietic stem cell transplantation.

Cytokine 2018 10 24;110:404-411. Epub 2018 May 24.

Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt; Bone Marrow Transplantation Unit, Nasser Institute Hospital for Research and Treatment, Cairo, Egypt.

Graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell transplantation (HSCT); cytokines are recognized as important mediators in its pathogenesis. In this study we investigated the role of cytokine gene polymorphisms on HSCT outcome. A total of 106 patient and 98 donors were genotyped by polymerase chain reaction sequence specific primers (PCR-SSP) based assay for tumor necrosis factor-α-308 (TNFα -308), interleukin (IL)-6-174, IL-10-1082, -819, -592, Interferon-γ+874 (IFN-γ+874), and transforming growth factor-β1 (TGF-β1) codon10 and 25 polymorphisms. Except one in each category, all patients and donors were TNFα -308 high producers and the majority were IL-6-174 high producers (93.3% and 90.8% respectively); a pattern that would alleviate any potential biological impact. Patient's IFN-γ+874 showed significant association with the development of chronic GVHD. Patients with IFN-γ +874 high producer showed an 8 folds likelihood to develop chronic GVHD as compared to those with IFN-γ+874 low producer predicted phenotype (95% CI: 1.59-40.2, p = 0.01). Patient's TGFβ1-codon 10 and 25 high/intermediate producers showed a lower incidence of acute GVHD though it did not achieve statistical significance (p = 0.065) on account of the low frequency of this genotype in our patients and donors (11.4 and 8.2% respectively). Other factors contributing to risk of GVHD included older age for both acute and chronic (p = 0.01 and 0.02 respectively) with age 24 as the best discriminating cutoff; CD34+ cell dose for chronic GVHD (p = 0.045) with a dose of 8 × 10/kg as the best discriminating cutoff; and conditioning regimen with Flu/Bu associated with the lowest incidence of acute GVHD (p = 0.003) and no impact on chronic GVHD. In conclusion the current study further indicates a potential role of some cytokine gene polymorphisms in the development of GVHD. The relative distribution of high and low producer genotypes in different ethnic groups contributes to their biological impact in different populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2018.05.003DOI Listing
October 2018

Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia.

Haematologica 2011 Jul 1;96(7):1049-54. Epub 2011 Apr 1.

Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.

Acute lymphoblastic leukemia is the major pediatric cancer in developed countries. To date most association studies of acute lymphoblastic leukemia have been based on the candidate gene approach and have evaluated a restricted number of polymorphisms. Such studies have served to highlight difficulties in conducting statistically and methodologically rigorous investigations into acute lymphoblastic leukemia risk. Recent genome-wide association studies of childhood acute lymphoblastic leukemia have provided robust evidence that common variation at four genetic loci confers a modest increase in risk. The accumulated experience to date and relative lack of success of initial efforts to identify novel acute lymphoblastic leukemia predisposition loci emphasize the need for alternative study designs and methods. The International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium includes 12 research groups in Europe, Asia, the Middle East and the Americas engaged in studying the genetics of acute lymphoblastic leukemia. The initial goal of this consortium is to identify and characterize low-penetrance susceptibility variants for acute lymphoblastic leukemia through association-based analyses. Efforts to develop genome-wide association studies of acute lymphoblastic leukemia, in terms of both sample size and single nucleotide polymorphism coverage, and to increase the number of single nucleotide polymorphisms taken forward to large-scale replication should lead to the identification of additional novel risk variants for acute lymphoblastic leukemia. Ethnic differences in the risk of acute lymphoblastic leukemia are well recognized and thus in assessing the interplay between inherited and non-genetic risk factors, analyses using different population cohorts with different incidence rates are likely to be highly informative. Given that the frequency of many acute lymphoblastic leukemia subgroups is small, identifying differential effects will realistically only be possible through multi-center pooled analyses. Here, we review the rationale for identifying genetic risk variants for acute lymphoblastic leukemia and our proposed strategy for establishing the International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2011.040121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3128225PMC
July 2011