X‐ray repair cross‐complementing group 1 (XRCC1), a coordinator protein of the DNA repair complex, is thought to be involved in cancer progression. This case–control study aimed to investigate the association of two biallelic single‐nucleotide polymorphisms (SNPs; Arg399Gln, Arg194Trp) of the XRCC1 gene with its tissue expression level and breast cancer (BC) risk in Egyptian women. This study included 100 BC female patients (case group 1) and 100 healthy females (control group 2). The XRCC1 tissue expression was assessed by immunohistochemistry (IHC). Genotyping of the two XRCC1 SNPs (Arg399Gln, Arg194Trp) using real‐time polymerase chain reaction (PCR) was also conducted. The XRCC1 expression level was significantly lower in cancerous tissues than adjacent non‐cancerous tissues (p < .001). The XRCC1 399Gln/Gln genotype, 399Gln allele, the dominant, and recessive models were significantly associated with lower XRCC1 expression in breast cancerous tissues and increased risk for BC (3.390‐, 1.965‐, 2.241‐, and 2.429‐folds, respectively). The XRCC1 399Gln/Gln genotype was associated with lower incidence of advanced tumor grade (OR: 0.06; 95%CI: 0.01–0.74; p = .028). Conversely, the XRCC1 Arg194Trp polymorphism did not show any significant association with either XRCC1 expression in breast cancer tissues or BC risk in all genetic models. The XRCC1 haplotypes, 399Gln/194Arg and 399Gln/194Trp, were associated with 1.800‐ and 1.675‐folds risk for BC, respectively. The XRCC1 gene polymorphism (Arg399Gln) is associated with reduced XRCC1 tissue expression and enhanced BC risk with a well‐differentiated nature in Egyptian women. Moreover, XRCC1 haplotypes, 399Gln/194Arg and 399Gln/194Trp, were associated with increased BC risk.
Introduction: Endometrial adenocarcinoma is characterized by a good prognosis. However, the disease response shows a significant heterogeneity. Treatment of endometrial cancer (EC) is still based on clinico-pathological parameters, which have limited role in risk stratification. There is a need for more determinant markers, such as L1 Cell Adhesion Molecule (L1CAM), to identify patients at higher risk of relapse and tailor a more convenient treatment. L1CAM has a capacity to enhance cell motility and promote tumor invasion in different malignancies. In Egypt, the incidence rate of EC is growing over time. Especially in Elgharbiah governorate (home of this study). L1CAM expression and Ki-67 was reported and compared with other clinico-pathological criteria. Method: Seventy-six female patients of endometrial carcinomas were involved in this prospective study. The patients were treated and followed up at Tanta University Hospitals in the period between January 2015 to April 2019. L1CAM expression and Ki-67 was detected by immuno-histochemical exam and compared with other clinico-pathological criteria. Survival was assessed and compared by Kaplan-Meier curves and log-rank test. Results: Positive L1CAM expression was detected in 17 patients (22.4%) and was significantly correlated with unfavorable prognostic factors such as higher stage and grade ( P= 0.021 and P =0.001 respectively), lympo-vascular invasion ( P <0.001), non-endometroid type ( P <0.027) and Ki-67 ( P= 0.003). Univariate analysis revealed that: positive L1CAM; higher tumor grade; high stage; and non-endometrioid type were significantly associated with shorter disease-free survival (DFS) but no significant correlation was detected between Ki-67 and DFS. In multivariate analysis, positive L1CAM remained statistically significant with DFS [P =0.045; 95%CI (1.028:11.17); HR=3.38]. Conclusion: Our study indicates that L1CAM expression and Ki-67 are significantly associated with poor tumor characteristics. L1CAM is significantly associated with shorter disease-free survival and may be a helpful tool as a part of a simple clinical molecular classification for EC.
Background: Colorectal carcinoma (CRC) is a burden problem in a developing country like Egypt since patients are usually admitted in late stage with bad prognosis and short overall survival. Because of genetic predisposition of CRC and introduction of advanced molecular techniques, efforts are directed to screen for potential pathogenic or disease-causing variants in CRC patients Methods: DNA was isolated from formalin fixed paraffin embedded tissue sections collected from 24 CRC confirmed diagnosed patients. TruSight CRC panel (Illumina) was used for detection of different variants in 15 genes. The generated reads were obtained from Illumina Miseq were clustered into single nucleotide polymorphism (SNPs) and small insertions/deletions (Indels). Further pathogenic variants with somatic and germline mutations were identified according to the recommended criteria. Some CRC patients were subjected to anti-EGFR target therapy.Results: Most of the variants were detected in TP53 gene 140 variants (65%); 105 short deletions none of them was pathogenic, 29 missense mutations and 6 SNPs at splicing sites. Next, ERBB2 has got 17 variants (8.8%) (missense and splicing), 8 of them were damaging disease causing variants. Besides, 16 pathogenic variants were identified in 12 patients (6 in TP53 and 7 in KRAS). Some pathogenic variants were not reported before in CRC e.g. TP53 C>A, rs121912654, Val157Phe. Additionally, patients carried different KRAS wild mutations showed variable response to anti-EGFR target therapy. Conclusion:The most affected pathway in CRC was TP53 pathway followed by ERBB2, NRAS, KRAS and PIK3CA genes. Variable response to target therapy suggested dependence on the type of pathogenic variant identified, also a possible role of ERBB2 which had a significant variant frequency.NRAS. The prevalence rate of TP53 mutation in Arab population is 52.5% compared to 47.5% in matched Western population [7]. TP53 mutations have roles in determining progression, invasiveness and also metastasis of CRC. So, CRC patients with mutant TP53 have more progressive phenotype and poorer survival than those with TP53 wild type [8]. The phosphatidylinositol 3-kinase/Akt/mammalian target of
Background/Aims: It is now known beyond doubt that viral hepatitis (caused by B or C virus) along with bilharzial infestation (mostly S. mansoni) are the most important factors responsible for the vast majority of morbidity and mortality in Egypt. Based upon the concept that oxidative stress plays a key role in the development and pathogenesis of chronic liver diseases, many of the factors known to have antioxidant properties are to be investigated for purpose of evaluating their role in the defense mechanisms against all oxidant brunts associated with liver diseases. Serum MDA was assayed as a famous marker of oxidative stress, while PON1 enzyme activities were investigated as a marker of antioxidant properties. The polymorphism at 55 and 192 position known to be associated with PON1 enzyme are also investigated in Egyptian normal and chronic liver patients, in order to elucidate whether such polymorphism has any effect on the enzyme activity, and consequently the state of hepatic affection. Whether routine assay of PON1 activity in chronic liver disease patients can be introduced as a non-invasive clue marker for diagnosis and rating the stage of hepatic affection is another aim of the present work. Methods: We studied 75 patients with chronic liver disease (25 patient with chronic Bilharziasis, 25 patients with chronic hepatitis C, 25 patients with mixed hepatitis C and bilharzial cirrhosis) and 25 apparently healthy controls. Serum paraoxonase activity and levels of the lipid peroxidation marker (serum malondialdhyde) were measured spectrophotomtrically. PON1 genotyping at positions 55 and 192 were analyzed by PCR, restriction fragment length polymorphism and agarose gel electrophoresis. Results: the present work showed that chronic liver disease (viral and/or bilharzial) are associated with elevated oxidative stress (as indicated by increased MDA level) together with reduced PON1-activities, which is regarded as an antioxidant tool. The frequency of investigated polymorphism at 55 and 192 position were found to be of no statistical significance between patients and control groups. The MDA and PON1 values did correlate with standard liver function. Conclusion: The present work could introduce the assay of PON1 activity in the serum as a non-invasive, specific and reliable marker in a trial to assess the state of liver affection in chronic hepatic diseases.
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