Impact of cell death pathway genes Fas 21377AA and FasL 2844CC polymorphisms on the risk of developing non-small cell lung cancer

Background: The signalling pathway Fas and FasL system plays a fundamental role in the regulation of apoptotic cell death and any disturbance of this pathway has been shown to promote immune escape and tumorigenesis. Many types of cancers show reduced expression of FAS and elevated FasL expression. The Fas21377G/A, and FasL2844T/C polymorphisms might be associated with increased risk of lung cancer. Objective: The interplay between genetic polymorphisms could participate in cancer development. This study aimed to examine the contribution of Fas21377AA and FasL2844CC genotypes to risk of developing lung cancer. Subjects and methods: A case-control study was conducted on 20 non small cell lung cancer (NSCLC) cases and 40 controls. Genotyping of Fas 21377AA and FasL 2844CC Single nucleotide polymorphisms (SNPs) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were done to all subjects. Results: The distribution of Fas and FasL genotypes showed a higher frequency of Fas AA genotype among patients compared to controls with an increased risk of lung cancer (OR 5.28; CI:1.35–20.65, P value .01). No statistically significant difference was found between patients and controls groups in respect to FasL genotypes. Gene to gene interaction between Fas and FasL genotypes showed significant differences between the patients and controls groups. As regards the combination between FasL TT+CT & Fas AA, FasL CC & Fas GG+GA and FasL CC & Fas AA genotypes where patients carrying FasL CC or Fas AA genotypes have increased risk to develop lung cancer, (OR 10.28, 95% CI; 1.68–62.74, P value .01), (OR 72, 95% CI; 5.55–132.99, P value .001) and (OR 9, 95% CI; 1.5–53.86, P value .01) respectively. The FasL-CC genotype showed 2.25 folds increased risk to develop lung cancer in non-smoker patients, P = .008. No correlation was found between the pathological types, the stage of lung cancer and the Fas and FasL genotypes. Conclusion: The interaction of the cell death pathway genes Fas and FasL polymorphisms could be associated with the risk of lung cancer, in the same respect Fas AA genotype could also potentiate this risk. Keywords: Cell death pathway genes, Fas FasL polymorphisms, Non small cell lung cancer, PCR-RFL

Association of genetic polymorphisms CYP2A6*2 rs1801272 and CYP2A6*9 rs28399433 with tobacco-induced lung Cancer: case-control study in an Egyptian population

Abstract Background Several studies have reported the role of CYP2A6 genetic polymorphisms in smoking and lung cancer risk with some contradictory results in different populations. The purpose of the current study is to assess the contribution of the CYP2A6*2 rs1801272 and CYP2A6*9 rs28399433 gene polymorphisms and tobacco smoking in the risk of lung cancer in an Egyptian population. Methods A case-control study was conducted on 150 lung cancer cases and 150 controls. All subjects were subjected to blood sampling for Extraction of genomic DNA and Genotyping of the CYP2A6 gene SNPs (CYP2A6*2 (1799 T > A) rs1801272 and CYP2A6*9 (− 48 T > G) rs28399433 by Real time PCR. Results AC and CC genotypes were detected in CYP2A6*9; and AT genotype in CYP2A6*2. The frequency of CYP2A6*2 and CYP2A6*9 were 0.7% and 3.7% respectively in the studied Egyptian population. All cancer cases with slow metabolizer variants were NSCLC. Non-smokers represented 71.4% of the CYP2A6 variants. There was no statistical significant association between risk of lung cancer, smoking habits, heaviness of smoking and the different polymorphisms of CYP2A6 genotypes. Conclusion The frequency of slow metabolizers CYP2A6*2 and CYP2A6*9 are poor in the studied Egyptian population. Our findings did not suggest any association between CYP2A6 genotypes and risk of lung cancer

The role of BRCA1-IRIS in the development and progression of triple negative breast cancers in Egypt: possible link to disease early lesion

Abstract Background Breast cancer is the most globally diagnosed female cancer, with the triple negative breast cancer (TNBC) being the most aggressive subtype of the disease. In this study we aimed at comparing the effect of BRCA1-IRIS overexpression on the clinico-pathological characteristics in breast cancer patients with TNBC or non-TNBC in the largest comprehensive cancer center in Egypt. Methods To reach this goal, we conducted an observational study at the National Cancer Institute (NCI), Cairo University (Cairo, Egypt). The data on all diagnosed breast cancer patients, between 2009 and 2012, were reviewed. BRCA1-IRIS expression measured using real time RT/PCR in these patients’ tumor samples was correlated to tumor characteristics, such as to clinico-pathological features, therapeutic responses, and survival outcomes. Results 96 patients were enrolled and of these 45% were TNBC, and 55% were of other subtypes (hereafter, non-TNBC). All patients presented with invasive ductal carcinomas. No significant difference was observed for risk factors, such as age and menopausal status between the TNBC and the non-TNBC groups except after BRCA1-IRIS expression was factored in. The majority of the tumors in both groups were ≤5 cm at surgery (p = 0.013). However, in the TNBC group, ≤5 cm tumors were BRCA1-IRIS-overexpressing, whereas in the non-TNBC group they were BRCA1-IRIS-negative (p = 0.00007). Most of the TNBC patients diagnosed with grade 1 or 2 were BRCA1-IRIS-overexpressing, whereas non-TNBCs were IRIS-negative (p = 0.00035). No statistical significance was measured in patients diagnosed with grade 3 tumors. Statistically significant difference between TNBCs and non-TNBCs and tumor stage with regard to BRCA1-IRIS-overexpression was observed. Presence of axillary lymph node metastases was positively associated with BRCA1-IRIS overexpression in TNBC group, and with BRCA1-IRIS-negative status in the non-TNBC group (p = 0.00009). Relapse after chemotherapy (p < 0.00001), and local recurrence/distant metastasis after surgery (p = 0.0028) were more pronounced in TNBC patients with BRCA1-IRIS-overexpressing tumors compared to non-TNBC patients. Finally, decreased disease-free survival in TNBC/BRCA1-IRIS-overexpressing patients compared to TNBC/BRCA1-IRIS-negative patients, and decreased overall survival in TNBC as well as non-TNBC patients was driven by BRCA1-IRIS overexpression. Conclusions TNBC/BRCA1-IRIS-overexpressing tumors are more aggressive than TNBC/BRCA1-IRIS-negative or non-TNBC/BRCA1-IRIS-overexpressing or both negative tumors. Further studies are warranted to define whether BRCA1-IRIS drives the early TNBC lesions growth and dissemination and whether it could be used as a diagnostic biomarker and/or therapeutic target for these lesions at an early stage setting