Genetic polymorphisms of human cytochrome P450 CYP1A1 in an Egyptian population and tobacco-induced lung cancerReport as inadecuate




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Genes and Environment

, 39:7

First Online: 07 January 2017Received: 28 September 2016Accepted: 08 December 2016

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.

KeywordsLung cancer CYP1A1 Polymorphisms Tobacco smoking AbbreviationsAsnAsparagines

CYPCytochrome P450

GSTGlutathione S-transferase

IleIsoleucine

NATN-acetyltransferase

NSCLCNon-small cell lung cancer

PAHPolycyclic aromatic hydrocarbons

SCLCSmall cell lung cancer

ThrThreonine

ValValine

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Author: Nada Ezzeldin - Dalia El-Lebedy - Amira Darwish - Ahmed El-Bastawisy - Mirhane Hassan - Shereen Abd El-Aziz - Mohamed Abdel

Source: https://link.springer.com/







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