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. 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. 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. 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.
Cytochrome P450 CYP1A1 helps detoxify the potential carcinogens in tobacco smoke, it was reported that polymorphisms in the coding gene result in variation in the expression and activity levels which alter metabolism and clearance of carcinogens and therefore modify cancer risk. In this work, we aimed to identify CYP1A1 gene polymorphisms associated with lung cancer in Egyptian population and to examine the interaction effect with Tobacco smoking in modulating disease risk. A case–control study was conducted on 150 unrelated lung cancer patients and 150 unrelated control subjects. Genomic DNA was extracted and sequencing analysis of CYP1A1 gene was performed on ABI PRISM 3100 genetic analyzer. Three variants in CYP1A1 gene were identified in heterozygous forms in lung cancer patients I462V, T461N and I286T. A combined variant T461N/ I462V associated with lung cancer and those who carried this variant were 2-times more likely to develop lung cancer (OR = 2.03, 95% CI = 1.81-2.29, P = 0.04), specially the non-small cell type (NSCLC) (OR = 2.20, 95% CI = 1.93–2.50, P = 0.02). Wild type was more frequent among smoker controls (83.3%) compared to smoker lung cancer patients (54.8%), P = 0.03. Association studies to examine the interaction effect of identified variants with Tobacco smoking in modulating disease risk showed no significant associations. Identified polymorphisms showed no significant implication on the stage or the prognosis of the disease. Our findings support that CYP1A1 polymorphisms play a role in the pathogenesis of lung cancer. In Egyptian population, CYP1A1 I462V, T461N and I286T variants were identified among lung cancer patients and combined T461N/ I462V was a risk variant for NSCLC in non smokers.
Introduction : Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and death. The most common cause of COPD is smoking. There is evidence suggesting that genetic factors influence COPD susceptibility and variants in several candidate genes have been significantly...
Aim of the study: Complement factor H (CFH) has been known to inhibit the complement pathway and to contribute to tumour growth by suppressing the anti-tumour cell mediated response in cell lines from several malignancies. We examined the association of Try402His single nucleotide polymorphism...
1 October 2012 in Journal of Bronchology & Interventional Pulmonology
Background: Airway smooth muscle contraction causes bronchial constriction and is the main cause of bronchospasm in response to stimulants in asthma patients. In this pilot study, we tested the possibility of using a commercially available neurotoxin—botulinum toxin A (BTX-A)—to reduce bronchial hyperreactivity in dogs. Methods: Two bronchoscopic sessions were conducted in 6 healthy mongrel dogs. In the first session, BTX-A (concentration 10 U/mL) was injected in small aliquots submucosally in 1 caudal lobe and its subsegments, leaving the other side as control. During the second bronchoscopy conducted 2 weeks later, the airway calibers of the treated and untreated sides were measured in each animal before and after instillation of methacholine in the airways to induce bronchial hyperreactivity (concentration 25 mg/mL). Results: The mean pretreatment diameter was 3.356 (±1.294) mm and 2.765 (±0.603) mm in the treated and untreated airways, respectively. After provocation with methacholine, the diameter of the treated airways was 1.985 (±0.888) mm versus 0.873 (±0.833) mm in the untreated airways (P=0.000). Local injection of BTX-A in the airway resulted in reduction of bronchial hyperreactivity by 58.6% (P=0.001). There were no complications resulting from the submucosal injection of BTX-A in the airways. Conclusions: Endobronchial injection of BTX-A reduces bronchial hyperreactivity in the airways of healthy dogs.
Introduction: TGF-b1 is a cytokine with many different effects on cell proliferation, differentiation and inflammation and can protect against the development of COPD. This work aims to study the association between COPD and the TGF-b1 gene genotypes. Material and methods: The study...