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

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.

Association of Cytochrome CYP1A1 Gene Polymorphisms and Tobacco Smoking With the Risk of Breast Cancer in Women From Iraq

“…The role of CYP1A1 polymorphisms in breast cancer risk in individuals, however, has been conflicting. Some studies have shown that CYP1A1 polymorphisms are significantly associated with breast cancer risk ( 13 , 34 , 36 ) consistent with this study. In this study, patients with either G or C allele carriers were approximately equally susceptible to breast cancer and the G and C allele carriers were under represented in the control group.…”

“…The polymorphism was evident in many different race and ethnic groups as in African-American ( 10 , 12 , 15 ), Chinese ( 14 , 16 ), Siberians ( 17 ), Canadians ( 19 ), Kashmiri and northern Indians ( 30 , 33 ), Hispanic-non-Hispanic white women ( 32 ), Egyptian Arabs [Ref. ( 34 ) and this study], and Japanese ( 35 ). On the other hand, the TT and AA wild homozygous genotypes as well as T and A allele frequencies were significantly higher among the control group which became more prevalent among smoking women with breast cancer.…”

Genetic Polymorphisms of the Human Cytochrome P450 1A1 (CYP1A1) and Cervical Cancer Susceptibility among Northeast Thai Women

“…As for m4 polymorphism, possible associations have been documented between the A allele and risk for lung cancer (Gallegos-Arreola et al, 2008;Shah et al, 2008;Ezzeldin et al, 2017), laryngeal squamous cell carcinoma (Gajecka et al, 2005) and thyroid cancer (Siraj et al, 2008). No association has been observed between m4 polymorphism and breast, colorectal, and gastric cancer (Li et al, 2004;Singh et al, 2007;Amrani et al, 2016, Little et al, 2006Agudo et al, 2014).…”

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

“…A case-control study was conducted that included 150 unrelated adult patients with primary lung cancer and 150 unrelated controls. The case series consisted of patients presented to NCI details of which have been described elsewhere [ 31 ]. Almost half of the patients seen at NCI-Cairo came from the Cairo metropolitan area, whereas the rest of the patients were from other regions in South and North Egypt.…”