Abstract
BackgroundCytochrome 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.MethodsA 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.ResultsThree 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.ConclusionOur 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.
Highlights
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 modify cancer risk
The aim of this work is 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
Our results showed an estimated risk for lung cancer 6.7 times greater in Egyptian smokers than in non-smokers compared to 2.61 times in a previous study [23] and an increased risk to develop lung cancer in males by 3.5-times than in females, which might be attributed to the higher incidence of smoking habit among males
Summary
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 modify cancer risk. 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. Most lung cancer patients demonstrate chromosomal abnormalities at the site of tumor suppressor genes or have mutations in known oncogenes [1]. There is a considerable interest in variants of genes that help detoxify the carcinogens in tobacco smoke, such as members of the cytochrome P450 (CYP), glutathione S-transferase (GST) and N-acetyltransferase (NAT) gene families [3]. Mutations at the substrate recognition sites may lead to changes in enzyme specificity [5]
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