Oral cancer susceptibility associated with the CYP1A1 and GSTM1 genotypes in Chilean individuals (original) (raw)
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Indian Journal of Clinical Biochemistry, 2010
Polycyclic aromatic hydrocarbons of tobacco require activation by phase I enzymes, such as cytochrome-P4501A1 (CYP1A1) to become an ultimate carcinogen, which are subjected to detoxification by phase II enzymes, especially glutathione S-transferases (GSTs). A study was designed to find whether genetic predisposition are risk modifiers of oral pathologies. The study included 102 cases with Oral Cancers (OCs), 68 cases with nonmalignant pathologies, 100 cases as control group. GSTM1 null genotype was associated with increased risk of OCs but not with benign pathologies. Deleted GSTT1 was associated with all pathologies. Both m1m2 and m2m2 polymorphisms of CYP1A1 were associated with oral pathologies.
Oral oncology, 1999
The genetic polymorphisms of CYP1A1 and GSTM1 genes among 100 Japanese patients with oral squamous cell carcinomas (SCC) were investigated to evaluate the role of genetic susceptibility in carcinogenesis of the oral cavity. The presence of the rare homozygote of CYP1A1, m2/m2, was significantly more frequent in the patient group (15.0%) than the control group (8.0%) (Odds ratio (ORs) = 3.6 95% Confidential Interval (CI): 1.4-9.5). The heterozygotic variant, m1/m2, was also frequently seen in oral SCC patients. This meant that the m2 allele was observed in more than half of the patients. The null genotype of GSTM1 was found in 43.0% of the patient group. This was not significantly different from the controls (40.0%). When the life time cigarette consumption dose of the patients was considered with respect to genotypes of CYP1A1, the mean smoking index (SI) of oral SCC patients with m2/m2 was found to be less than half of the mean SI among the patients with m1/m1 genotype (P < 0.02...
Journal of Oral Pathology and Medicine, 2002
The importance of the CYP1A1 polymorphisms at exon 7 (Ile/Val) and 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-untranslated region (3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-UTR) has been controversial in oral squamous cell carcinoma (OSCC) or head and neck SCC (HNSCC) denoting the value of exploring the correlation between these polymorphisms and risk of betel/smoking associated OSCC. It is also important to evaluate the association between CYP1A1 polymorphisms and susceptibility of oral precancerous lesion (OPL) to confirm the findings in OSCC cases. We examined polymorphic prevalence of CYP1A1 at exon 7 (Ile/Val) and 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-UTR in 106 cases with OSCC, 60 cases with OPL, and 146 controls. DNA isolated from surgical specimens and whole blood was used for PCR-based genotyping. The prevalence of the CYP1A1 A/G genotype (Ile/Val) and G/G genotype (Val/Val) in exon 7 of cases with OSCC (79.2 and 7.6%) and OPL (68.3 and 10%) were significantly higher than in controls (53.4 and 1.4%) (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). The novelty of the present study is that we identified the onset age of OSCC in CYP1A1 A/G genotype to be significantly younger than that in A/A genotype (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). No significant difference was seen between cases and controls regarding the polymorphisms at 3&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-UTR. The findings indicate that the individuals with the CYP1A1 exon 7 containing G allele were at increased risk for OSCC and OPL.
Cancer Epidemiology Biomarkers & Prevention
Tobacco use is causally associated with cancers of the lung, larynx, mouth, esophagus, kidneys, urinary tract, and possibly, breast. Major classes of carcinogens present in tobacco and tobacco smoke are converted into DNA-reactive metabolites by cytochrome P450 (CYP)-related enzymes, several of which display genetic polymorphism. Individual susceptibility to cancer is likely to be modified by the genotype for enzymes involved in the activation or detoxification of carcinogens in tobacco and repair of DNA damage. We summarize here the results of case-control studies published since 1990 on the effects of genetic variants of CYP1A1, 1A2, 1B1, 2A6, 2D6, 2E1, 2C9, 2C19, 17, and 19 alone or in combination with detoxifying enzymes as modifiers of the risk for tobacco-related cancers. The results of studies on gene-gene interactions and the dependence of smoking-related DNA adducts on genotype were also analyzed. Some CYP variants were associated with increased risks for cancers of the lun...
Genes and environment : the official journal of the Japanese Environmental Mutagen Society, 2017
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 =...
The International Journal of Biological Markers, 2016
ORIGINAL RESEARCH ARTICLE unknown chemicals which produce highly carcinogenic compounds when activated. The process of carcinogen metabolism is mediated by phase I enzymes referred to as cytochrome P450 (CYP). Enzymes of the CYP family are heme-containing enzymes present in both hepatic and extrahepatic tissues (5). Among the various CYP genes, CYP1A1 located on chromosome 15q22-q24 (6) encodes the enzyme aryl hydrocarbon hydroxylase, which is responsible for the activation of polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene. Once activated, PAH metabolites act as powerful carcinogens which then bind to DNA to form adducts and produce somatic mutations in either tumor suppressor genes or oncogenes and trigger the process of carcinogenesis and hence cancer initiation. The CYP1A1 gene is polymorphic and has been shown to have 15 different allelic variants (7). Four of these variants, designated as m1, m2, m3 and m4, have been widely studied in Asian and Caucasian populations as risk factors for lung carcinogenesis. The m1 and m2 polymorphisms were found to be involved in lung carcinogenesis (8). The CYP1A1 m1 (rs4646903) polymorphism has been associated with elevated enzyme activity due to a single base point mutation at nucleotide position 3801 that results in transition of thymine to cytosine in
Association of cytochrome P450 1B1 haplotypes with head and neck cancer risk
Environmental and molecular mutagenesis, 2017
Genetic polymorphisms have been reported in several cytochrome P450 (CYP) genes, including CYP1B1 which metabolically activates procarcinogens present in tobacco to carcinogenic intermediates. This study used a case-control approach in North Indian population to determine associations between genetic variants in CYP1B1 and risk of Head and Neck Squamous Cell Carcinoma (HNSCC). We examined the genotype and haplotype frequencies at various single-nucleotide polymorphisms (SNPs), including SNPs previously reported in the promoter region and intron 1 of CYP1B1 in Caucasians. Using cycle sequencing, 9 SNPs were identified in the promoter region, intron 1, and exons 2 and 3. Haplotype analysis revealed that 5 SNPs (those in the promoter region, intron, and Arg48Gly and Ala119Ser in exon 2) were in strong linkage disequilibrium (LD). Cases with the T-A-T-G-T haplotype were significantly associated with increased risk of HNSCC. Interestingly, qRT-PCR studies revealed a significant increase ...
Genetic polymorphisms in tobacco-metabolizing genes may modulate the risk of head and neck cancer (HNC). In Northeast India, head and neck cancers and tobacco consumption remains most prevalent. The aim of the study was to investigate the combined effect of cytochrome P450 1A1 (CYP1A1) T3801C, glutathione S-transferases (GSTs) genes polymorphisms and smoking and tobacco-betel quid chewing in the risk of HNC. The study included 420 subjects (180 cases and 240 controls) from Northeast Indian population. Polymorphisms of CYP1A1 T3801C and GST (M1 & T1) were studied by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and multiplex PCR, respectively. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approach were applied for statistical analysis. LR analysis revealed that subjects carrying CYP1A1 TC/CC + GSTM1 null genotypes had 3.52-fold (P < 0.001) increase the risk of head and neck squamous cell carcinoma (HNSCC). Smokers carrying CYP1A1 TC/CC + GSTM1 null and CYP1A1 TC/CC + GSTT1 null genotypes showed significant association with HNC risk (odds ratio [OR] = 6.42; P < 0.001 and 3.86; P = 0.005, respectively). Similarly, tobacco-betel quid chewers carrying CYP1A1 TC/CC + GSTM1 null genotypes also had several fold increased risk of HNC (P < 0.001). In MDR analysis, the best model for HNSCC risk was the four-factor model of tobacco-betel quid chewing, smoking, CYP1A1 TC/CC, and GSTM1 null genotypes (testing balance accuracy [TBA] = 0.6292; cross-validation consistency [CVC] = 9/10 and P < 0.0001). These findings suggest that interaction of combined genotypes of carcinogen-metabolizing genes with environmental factors might modulate susceptibility of HNC in Northeast Indian population.
CYP1A1 genotypes and haplotypes and risk of oral cancer: a case-control study in South Indians
Genetics and Molecular Biology, 2012
The CYP1A1 gene encodes for the enzyme, aryl hydrocarbon hydroxylase, which is involved in the biotransformation of various aromatic tobacco precarcinogens. In the present study, the association between CYP1A1 gene polymorphisms (IVS1-728G > A, Thr461Asn and Ile462Val), and the risk of oral cancer, was examined among 157 patients with oral cancer and 132 age-matched controls, in a south Indian population. The strength of the association between CYP1A1 variants and oral cancer was estimated by logistic regression. It was found that Thr461Asn was not polymorphic. Both IVS1-728G > A and Ile462Val frequencies were consistent with Hardy-Weinberg equilibrium in the control group. There were no significant differences in genotype or haplotype frequencies between controls and cases with oral cancer. Hence, CYP1A1 SNPs can be considered as not being associated with oral cancer at either the genotype or haplotype levels in the population studied.