Association of cytochrome P450 1B1 haplotypes with head and neck cancer risk (original) (raw)

Polymorphisms of the CYP1A1 and CYP2E1 genes in head and neck squamous cell carcinoma risk

Polymorphisms in genes that encode P450 cytochrome enzymes may increase carcinogen activation or decrease their inactivation and consequently, promote the development of cancer. The aims of this study were to identify the MspI-CYP1A1, PstI-CYP2E1 and DraI-CYP2E1 polymorphisms in patients with head and neck cancer and to compare with individuals without cancer; to evaluate the association of these polymorphisms with risk factors and clinical histopathological parameters. In the study group, 313 patients were evaluated for CYP1A1, 217 for CYP2E1 (PstI) and 211 for CYP2E1 (DraI) and in the control group 417, 334 and 374 individuals, respectively. Molecular analysis was performed by PCR–RFLP technique , and chi-square and multiple logistic regression tests were used for statistical analysis. The result of analysis regarding individuals evaluated for CYP1A1 (MspI) showed that age (OR: 8.15; 95% CI 5.57–11.92) and smoking (OR: 5.37; 95% CI 3.52–8.21) were predictors for the disease; for the CYP2E1 (PstI and DraI), there were associations with age (PstI-OR: 9.10; 95% CI 5.86–14.14/

Genetic polymorphism of cytochrome P4501A1 and susceptibility to oral squamous cell carcinoma and oral precancer lesions associated with smoking/betel use

Journal of Oral Pathology and Medicine, 2002

The importance of the CYP1A1 polymorphisms at exon 7 (Ile/Val) and 3'-untranslated region (3'-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'-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 < 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 < 0.01). No significant difference was seen between cases and controls regarding the polymorphisms at 3'-UTR. The findings indicate that the individuals with the CYP1A1 exon 7 containing G allele were at increased risk for OSCC and OPL.

Influence of the CYP1A1 T3801C Polymorphism on Tobacco and Alcohol-Associated Head and Neck Cancer Susceptibility in Northeast India

Background: Tobacco and alcohol contain or may generate carcinogenic compounds related to cancers. CYP1A1 enzymes act upon these carcinogens before elimination from the body. The aim of this study was to investigate whether CYP1A1 T3801C polymorphism modulates the relationship between tobacco and alcohol associated head and neck cancer (HNC) susceptibility among the northeast Indian population. Materials and Methods: One hundred and seventy histologically confirmed HNC cases and 230 controls were included within the study. The CYP1A1 T3801C polymorphism was determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis. Results: The CYP1A1 CC genotype was significantly associated with HNC risk (P=0.045). A significantly increased risk of HNC (OR=6.09; P<0.0001) was observed in individuals with combined habits of smoking, alcohol drinking and tobacco-betel quid chewing. Further, gene-environment interactions revealed enhanced risks of HNC among smokers, alcohol drinkers and tobacco-betel quid chewers carrying CYP1A1 TC or CC genotypes. The highest risk of HNC was observed among smokers (OR=7.55; P=0.009) and chewers (OR=10.8; P<0.0001) carrying the CYP1A1 CC genotype. In MDR analysis, the best model for HNC risk was the three-factor model combination of smoking, tobacco-betel quid chewing and the CYP1A1 variant genotype (CVC=99/100; TBA=0.605; P<0.0001); whereas interaction entropy graphs showed synergistic interaction between tobacco habits and CYP1A1. Conclusions: Our results confirm that the CYP1A1 T3801C polymorphism modifies the risk of HNC and further demonstrated importance of gene-environment interaction.

Genetic polymorphisms in the Cytochrome P450 family and squamous cell carcinoma of the oral cavity, pharynx and larynx

Revista do Colégio Brasileiro de Cirurgiões, 2014

Objective:To analyze the genetic polymorphisms of the cytochrome P450 family and their relationship with squamous cell carcinoma of the oral cavity, pharynx and larynx.Methods: We present a narrative literature review, conducted in Pubmed, Lilacs and Cochrane Databases of articles published in the last five years correlating genetic polymorphisms of the cytochrome P450 family and cancer risk in different populations worldwide.Results: We initially found 65 articles and, after selection criteria, 20 case-control studies with various populations worldwide were eligible. The most studied polymorphisms were those of CYP2E1 and CYP1A1 subfamilies. There is little about the other subfamilies. The association found between polymorphisms and cancer risk amounted to a countless number of variables, amongst them: population, selection methods, racial factors and different modes of exposure to carcinogens, genotyping methods, and nomenclature of the polymorphisms.Conclusion: so far, there is n...

Tobacco carcinogen-metabolizing genes CYP1A1, GSTM1, and GSTT1 polymorphisms and their interaction with tobacco exposure influence the risk of head and neck cancer in Northeast Indian population

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 gene polymorphism (6235 T/C) in head and neck cancer of an indonesian population

Journal of International Dental and Medical Research, 2017

One of the genes that plays a role in the formation of cancer cells is CYP1A1 (cytochrome P450, family 1, subfamily A, polypeptide 1) CYP1A1 codes for enzymes that have an important role in activating or detoxifying carcinogenic elements in tobacco and other compounds. This study aimed to investigate the potential association of CYP1A1 gene polymorphism and the incidence of head and neck cancer (HNC) by comparing the polymorphism distribution in HNC patients and healthy controls of an Indonesian population. Polymerase Chain Reaction – Restriction Fragment length Polymorphism (PCR-RFLP) techniques with the MspI enzyme were used for genotyping of the single nucleotide polymorphisms (SNPs) of CYP1A1 (rs4646903) in HNC patients and healthy controls. The frequencies of the TT genotype were 34% for HNC and 30% for the healthy controls; CT was 56% for HNC and 66% for the healthy controls; homozygote CC was 10% for HNC and 4% for the healthy controls. There is no significant association of ...

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

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 =...

Association of polymorphism in cytochrome P450 2C9 with susceptibility to head and neck cancer and treatment outcome

Applied Translational Genomics, 2014

The present case-control study involving 750 cases and equal number of healthy controls investigates the association of polymorphism in cytochrome P450 2C9 (CYP2C9) with head and neck squamous cell carcinoma (HNSCC) and response in patients receiving chemotherapy or combination of radio-chemotherapy. The frequency of heterozygous or homozygous genotypes of CYP2C9*2 & CYP2C9*3, which leads to the poor metabolizer (PM) genotype was significantly higher in HNSCC cases when compared to the healthy controls resulting in significantly increased risk in the cases. Tobacco use in the form of tobacco smoking or tobacco chewing was found to increase the risk several fold in cases when compared to the non-tobacco users. Likewise, alcohol intake in cases with variant genotypes of CYP2C9*2 or CYP2C9*3 also significantly increased the HNSCC risk in cases when compared to non-alcohol users. Further, majority of the cases carrying variant alleles of both CYP2C9*2 or CYP2C9*3 were found to respond poorly to the chemotherapy or combination of radio-chemotherapy. The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome.

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.

Genetic polymorphisms in cytochrome P450 genes are associated with an increased risk of squamous cell carcinoma of the larynx and hypopharynx in a Chinese population

Cancer Genetics and Cytogenetics, 2010

The purpose of this study was to examine whether functional polymorphisms in the cytochrome P450 (CYP) enzyme genes affect the risk of developing larynx and hypopharynx squamous cell carcinoma (SCC). We investigated CYP1A1, CYP1B1, CYP2E1, and CYP3A4 polymorphisms in 278 patients with laryngeal and hypopharyngeal SCC and 278 control subjects by polymerase chain reactionerestriction fragment length polymorphism (PCR-RFLP). Subjects with the CYP1A1 3798CC or TC genotype had an odds ratio (OR) of 3.26 (95% confidence interval CI 5 1.76 À 6.03) or 1.56 (95% CI 5 1.06 À 2.31), compared with those with the TT genotype. An increased risk was also associated with the CYP1A1 462Val/Val genotype (OR 5 2.39, 95% CI 5 1.11 À 5.16), compared with the TT genotype. Haplotype analysis suggested a synergistic effect of these two polymorphisms. A multiplicative joint effect between the CYP1A1 3798 T O C polymorphism and smoking was observed. The OR (95% CI) of the TC or CC genotype for nonsmokers and smokers of O20 pack-years were 1.85 (0.99 À 3.44) or 8.15 (4.35 À 15.26), respectively (P trend ! 0.05). The CYP1A1 single-nucleotide polymorphisms are associated with an increased risk of developing smoking-related laryngeal and hypopharyngeal SCC in a Han Chinese population. Ó