Ola Khorshid

Tumor necrosis factor alpha-308 and Lymphotoxin alpha+252 genetic polymorphisms and the susceptibility to non-Hodgkin lymphoma in Egypt.

Genetic polymorphism within the regulatory regions of tumor necrosis factor-alpha (TNF-α) and Lymphotoxin-alpha (LT-α) may be involved in the development of lymphoid malignancies. The aim of the current study was to investigate the effect of TNFα-308 and LTα+252 genetic polymorphism on susceptibility to non-Hodgkin lymphoma (NHL) in Egypt. Genotyping of the studied genes by restriction fragment length polymorphism polymerase chain reaction was conducted on 84 NHL and 100 healthy controls and revealed that TNFα-308 homotype (AA) was significantly higher in NHL patients and conferred sixfold increased risk of NHL (OR=5.9, 95%CI=2.3-16.1). Moreover, TNFα/LTα high-producer haplotypes were significantly higher in NHL patients and conferred increased risk of NHL (OR=4.59, 95%CI=2.19-9.42).

Association of cytotoxic T-lymphocyte antigen 4 genetic polymorphism, hepatitis C viral infection and B-cell non-Hodgkin lymphoma: an Egyptian study

Abstract Genetic and environmental factors are involved in the pathogenesis of non-Hodgkin lymphoma (NHL). The present study aimed to investigate the association between cytotoxic T-lymphocyte antigen 4 (CTLA-4) genetic polymorphism, hepatitis C virus (HCV) infection and B-cell NHL risk in Egypt. Genotyping of CTLA-4 single nucleotide polymorphisms (SNPs) was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay for 181 adult patients with B-NHL and 200 controls. Our study revealed that CTLA-4 + 49 A/G polymorphism conferred increased risk of B-NHL (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.36–2.565). The prevalence of HCV infection in individuals harboring the mutant genotype + 49 A/G and − 318 C/T SNPs was higher in patients with B-NHL and was associated with increased risk of B-NHL (OR = 2.79, 95% CI = 1.24–6.93 for + 49 A/G and OR = 3.9, 95% CI = 1.01–15.98 for − 318 C/T). In conclusion, some SNPs of CTLA-4 are genetic risk factors for B-NHL. Moreover, this study identified an association of CTLA-4 + 49 A/G and − 318 C/T promoter polymorphisms with HCV infection.

Aberrant expression of miRNAs predicts recurrence and survival in stage-II colorectal cancer patients from Egypt

BackgroundPatients with stage II CRC have a varying survival outcome. Therefore, it is critical to identify prognostic biomarkers that can define more aggressive forms of the disease. We assessed the expression levels of five miRNAs that have been previously addressed in relation to the development and progression of solid and hematological tumors.MethodsWe measured the expression levels of miR-21, miR-137, miR-145, miR-320 and miR-498in stage II CRC patients from Egypt (124 tissues and 41 blood samples) by quantitative real time PCR (qPCR). The results were correlated with relevant clinicopathological factors, response to treatment and survival rates of the patients.ResultsmiR-137, miR-145 and miR-320 were significantly reduced in 39.5%, 48.4% and 52.4%; respectively whereas miR-21 and miR-498 were significantly overexpressed in 48.4% and 40.3% of the CRC tissues compared to the control group. In patients’ blood, miR-137, miR-145 and miR-320 were significantly reduced in 46.3%, 46.3% and 51.2%; respectively whereas mir-21 and miR-498 were significantly overexpressed in 46.3% and 43.9% of the cases, respectively. The concordance between tissue and blood was weak for miR-320 and miR-145 (kappa 40-65%), intermediate for miR-498 and miR-137 (kappa 65-75%) and strong for miR-21 (kappa 75-85%). In univariate analysis performance status, over-expression of miR-21 and miR-498 and reduced miR-137, miR-145, and miR-320 associated significantly with reduced DFS and OS. However, in multivariate analysis, miR-498 and miR-320 were independent prognostic factors for DFS whereas miR-21 was independent prognostic factors for OS.ConclusionsmiRNAs play an important role in the development and progression of stage II CRC. A five markers panel (miR-21, miR-498, miR-137, miR-145 and miR-320) can predict recurrence and survival in stage II CRC patients from Egypt.

TSC gene expression in the newly diagnosed Egyptian acute leukemia patients

TSC (tuberous sclerosis) complex is the major negative regulator of mTOR which activates cell cycle progression leading to uncontrolled growth. Acute leukemias are very heterogeneous as a group of hematological malignancies; they arise as a result of pled up genetic alterations. To study TSC gene expression in acute leukemia patients. Sixty-two Egyptian de no novo adult acute leukemia patients were assessed using SYBR green quantitative PCR as well as 22 controls. Correlation of TSC gene expression with response rate, other prognostic factors, and RFS was assessed. TSC1/TSC2 showed higher gene expression in acute leukemias compared to controls. TSC1 was significantly higher in T-ALL while TSC2 was significantly higher in B-ALL. Expression did not show significant correlation to known prognostic factors. TSC1/TSC2 overexpression might be implicated in the process of leukemogenesis.

Association of IL-2-330T/G and IL-10-1082A/G genetic polymorphisms with B NHL in a cohort of Egyptians

Objective: Polymorphisms in the interleukin (IL)-2 and IL-10 genes are known to be associated with susceptibility to different immune-dysregulated disorders and cancers such as non-Hodgkin lymphoma (NHL). To explore the possible association between IL-2-330T/G and IL-10-1082A/G single-nucleotide polymorphisms and the susceptibility to B-cell NHL (B-NHL) in Egyptians, we conducted a case-control study. Materials and Methods: Genotyping of the studied genetic variations was done for 100 B-NHL patients as well as 100 age- and sex-matched healthy controls. Results: The IL-2 variant allele occurred at a significantly higher rate in patients than controls and was associated with susceptibility to B-NHL [odds ratio (OR): 1.91, 95% confidence interval (CI): 1.28-2.85]. It was also associated with advanced performance status score. IL-2 polymorphism conferred an almost threefold increased risk of diffuse large B-cell lymphoma (OR: 2.64, 95% CI: 1.35-5.15) and a fourfold increased risk of indolent subtypes (OR: 4.34, 95% CI: 1.20-15.7). The distribution of IL-10-1082A/G genotypes in our patients was close to that of the controls. Co-inheritance of the variant genotypes of IL-2 and the common genotype of IL-10 conferred an almost sixfold increased risk (OR: 5.75, 95% CI: 1.39-23.72), while co-inheritance of the variant genotypes of IL-2 and IL-10 conferred fivefold increased risk of B-NHL (OR: 5.43, 95% CI: 1.44-20.45). The variant genotypes of IL-2-330T/G and IL-10-1082A/G had no effect on the disease-free survival of B-NHL patients. Conclusion: The present study highlights the possible involvement of the IL-2-330T/G genetic polymorphism in the susceptibility to B-NHL in Egypt, especially indolent subtypes. Moreover, IL-10-1082A/G is not a molecular susceptibility marker for B-NHL in Egyptians.

Micro-RNAs in stage II colorectal cancer: Is there any role?

566 Background: Patients with stage II CRC have a varying survival outcome. Therefore, it is critical to identify new prognostic biomarkers that can help to identify more aggressive forms of the disease. The aim of this study was to identify the potential prognostic value of miRNAs in patients with stage II CRC. Methods: The study included 124 patients with stage II CRC who attended the NCI - Medical Oncology clinics, received treatment and followed-up during the period from January 2004 to December 2014. The expression levels of the five studied miRNAs were examined by qRT-PCR analysis. Additionally, blood samples were drawn from 41 patients recruited in the study in the last 3 years of recruitment to assess the level of miRNAs in blood. Results: In tumor tissues of 124 patients, miR-137, miR-145 and miR-320 were significantly under-expressed in 39.5%, 38.4% and 52.4% of cases, respectively while miR-21 and miR-498 were significantly over-expressed in 48.4% and 40.3%, respectively. On the other hand, ass...

Association of Caspase 8 and Caspase 10 Genetic Polymorphisms with B-cell Non Hodgkin's Lymphoma in Egypt: A Case-Control Study

Background and purpose: Non-Hodgkin lymphomas are closely related diseases with distinctive morphologic, immunophenotypic, genetic, and clinical features. Genetic susceptibility studies of NHL are mandatory to identify at risk populations and to clarify important disease mechanisms. Caspase genes play a key role in regulation of apoptotic cell death, and dysregulation of this signaling pathway has been shown to participate in tumorigenesis. The current study aimed at defining the role of Caspase 8-D302H, Caspase 8-652 6N ins/del and Caspase 10-I522L genetic polymorphisms as risk factors for NHL and their possible role as genetic prognostic markers. Methods: The present study included 100 Egyptian B-cell NHL patients and 100 healthy controls. Genotyping of the studied genes was performed by polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) technique. Data was analyzed using SPSS statistical package version 15. Results: The study revealed that CASP8-D302H mutant genotypes were significantly higher in NHL patients when compared to the controls and conferred increased risk of NHL. For CASP8-652 6N ins/del and Casp10- I522L, there was no statistical difference in the distribution of the different genotypes between NHL cases and the controls. Furthermore, there were no statistical differences between NHL patients harboring the wild or mutant genotypes of the studied genes as regards their response to therapy. Conclusions: CASP8-D302H genetic polymorphism represents a genetic risk factor for NHL in Egyptian population. Hopefully, better understanding of the functional consequences of caspase genes polymorphism would provide a foundation for future studies of the possible role of these genes in lymphomagenesis.