Abstract
BackgroundSeveral 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.MethodsA 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.ResultsAC 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.ConclusionThe 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.
Highlights
Several studies have reported the role of Cytochrome P450 2A6 (CYP2A6) genetic polymorphisms in smoking and lung cancer risk with some contradictory results in different populations
Cytochrome P450 2A6 (CYP2A6), one of the forms of CYP expressed in the human respiratory tract, is the main enzyme involved in the metabolic activation of tobacco-specific nitrosamines to their carcinogenic forms [2]
It was found in one case of lung cancer; a non-smoker male diagnosed as adenocarcinoma (Fig. 2)
Summary
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. Cytochrome P450 2A6 (CYP2A6), one of the forms of CYP expressed in the human respiratory tract, is the main enzyme involved in the metabolic activation of tobacco-specific nitrosamines to their carcinogenic forms [2]. The existence of a CYP2A6 genetic polymorphism was suggested by evidence that there was extensive inter individual difference in the capacity of coumarin 7-hydroxylation [4, 5]. Detecting the alleles of CYP2A6 can help us to describe different smoking behaviors and smoking-related diseases among individuals [6]. CYP2A6*6, CYP2A6*7, CYP2A6*9, CYP2A6*10, CYP2A6*11, &, CYP2A6*13 are known to lead to reduced enzymatic activities while 5 variants (CYP2A6*2, CYP2A6*4, CYP2A6*5, CYP2A6*12, & CYP2A6*20) produce no functional enzyme [2, 9,10,11,12]
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