Genetic Polymorphism in Cytochrome P450 1B1 in a Spanish Population (original) (raw)
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Investigation of CYP1B1*3 and CYP1B1*4 polymorphisms in a Turkish population
Health Sciences Quarterly
CYP1B1 is a P450 enzyme involved in activating pro-carcinogens to carcinogens as well as estrogen metabolism. In order to examine the effect of CYP1B1 on cancer metabolism, it should be compared with healthy individuals and whether the polymorphism between healthy individuals and sick individuals is significant. This study aims to screen the CYP1B1*3 and CYP1B1*4 polymorphisms of a group of individuals who have not been diagnosed with cancer to examine the genetic differences of metabolic enzymes in the Turkish population.This study is a cross-sectional type descriptive study.The study included 295 patients without a cancer diagnosis. The research sample includes patients who applied to Ankara University Medical Faculty Hospital and Afyonkarahisar Health Sciences University Research and Application Hospital. The individuals signed voluntary consent forms before participation, and 3 ml blood samples were taken from each. DNA samples were obtained using a DNA isolation kit, and then p...
Association of CYP1B1 genetic polymorphism with incidence to breast and lung cancer
Pharmacogenetics, 2000
Cytochrome P450 1B1 (CYP1B1) participates in the metabolic activation of a number of procarcinogens including benzo[a]pyrene and the hydroxylation of 17â-estradiol at the C-4 position. In this study, we investigated the association between CYP1B1 genetic polymorphism and breast or lung cancer incidence. The Ala-Ser polymorphism at codon 119 in presumed substrate recognition site 1 was signi®cantly associated with the incidence of breast or squamous cell carcinoma of the lung. On the other hand, Leu-Val polymorphism at codon 432 did not show any association to the cancers. An allele containing both Ala and Leu simultaneously, comprised 75% of alleles among 315 Japanese healthy controls, was signi®cantly inversely associated with breast cancer incidence. When expressed in a recombinant system, this CYP1B1 cDNA showed the lowest 17â-estradiol 4-hydroxylase activity among four different variant forms of CYP1B1. Thus, inter-individual differences in activation of procarcinogens or metabolism of oestrogen originating from genetic polymorphisms of the human CYP1B1 gene may contribute to the susceptibility of human cancers.
Anticancer research
Genetic polymorphisms of metabolizing enzymes may affect the risk of cancer formation in humans. Since the diet can contain polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HAs), the relationship between polymorphisms of enzymes involved in PAH and HA metabolism and the occurrence of sporadic colorectal cancer was studied. Five hundred colorectal cancer patients and 500 controls were genotyped for cytochrome P450 enzymes (CYP) 1A1 Ile/Val, CYP 1A2*1F, CYP 2E1 c1/c2, microsomal epoxy hydrolase (mEH) exon 3 Tyr113His and exon 4 His139Arg polymorphisms by allele-specific polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism (RFLP). The presence of CYP 1A1 Val, CYP 2E1 c2 and mEH exon 3 His alleles was statistically significantly associated with the occurrence of colorectal cancer (OR: 1.44 95% CI: 1.04-2.00; OR: 1.74 95% CI: 1.15-2.65; OR: 1.79 95% CI: 1.10-2.92, respectively). These findings suggest that allelic polymorphism of metabolizing en...
Cytochrome P450 1A1 genetic polymorphisms as cancer biomarkers
Indian Journal of Cancer, 2015
Phase I metabolic enzyme CYP1A1 plays an important role in xenobiotics metabolism and has been extensively studied as a cancer risk biomarker. CYP1A1 is polymorphic and its four variants, e.g., CYP1A1* 2 A, CYP1A1* 2C, CYP1A1* 3 and CYP1A1* 4 with trivial names m1, m2, m3, and m4 respectively, are most commonly studied for cancer link. Gene-gene interaction studies combining polymorphisms of this enzyme with those of phase II detoxifying enzymes, especially glutathione S-transferases (GSTs) revealed greater risk for cancer susceptibility. Variants of CYP1A1 have also been found to be associated with chemotherapeutic adverse-effects. Results of these studies, however, remained largely contradictory mainly because of lack of statistical power due to involvement of small sample size. Strongly powered experimental designs involving gene-gene, gene-environment interactions are required in order to validate CYP1A1 as reliable cancer-biomarker.
Genetic polymorphism of cytochrome P450 2E1 in the Turkish population
Cell Biochemistry and Function, 2001
CYP 2E1 is involved in metabolic activation of carcinogenic N-nitrosamines, benzene, urethane and other low molecular weight compounds. CYP2E1 gene is present in the population in various polymorphic forms. We detected the RFLP of the human CYP2E1 gene with the restriction endonuclease PstI, RsaI and DraI in a group of 153 Turkish individuals. According to the results of the PstI/RsaI analysis, 96.07% of the subjects were of the c1/c1 genotype, and 3.93% were of the c1/c2 genotype. In the DraI RFLP analysis, 84.30% DD genotype, 15.03% CD genotype and 0.66% CC genotype were determined. The data obtained may be useful in epidemiological studies of the in¯uence of CYP2E1 polymorphism on carcinogenesis.
Anticancer research, 2011
Polymorphisms in genes encoding enzymes involved in xenobiotic metabolism and/or in cellular defenses against carcinogen-induced DNA damage play an important role in determining individual cancer susceptibility. However, their distribution and association with cancer susceptibility can vary in different populations. A case-control study including 290 cancer patients (cases) and 242 controls was performed to evaluate the relationship between polymorphisms of cytochrome P450 (CYP)1A1 and CYP2E1 and X-ray repair complementing defective repair in Chinese hamster cells (XRCC)1 genes and the risk of developing cancer in a Southern Italian (Basilicata) population. Genomic DNA was isolated from 5 ml whole blood and genotyping was performed using a PCR-RFLP technique. No significant differences were observed in the distribution of the CYP1A1, CYP2E1 and XRCC1 gene polymorphisms between the cases and controls in the population under study. The distribution of CYP1A1, CYP2E1 and XRCC1 gene pol...
Archives of Industrial Hygiene and Toxicology, 2009
Genetic Polymorphism of Metabolic Enzymes P450 (CYP) as a Susceptibility Factor for Drug Response, Toxicity, and Cancer RiskThe polymorphic P450 (CYP) enzyme superfamily is the most important system involved in the biotransformation of many endogenous and exogenous substances including drugs, toxins, and carcinogens. Genotyping forCYPpolymorphisms provides important genetic information that help to understand the effects of xenobiotics on human body. For drug metabolism, the most important polymorphisms are those of the genes coding for CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5, which can result in therapeutic failure or severe adverse reactions. Genes coding for CYP1A1, CYP1A2, CYP1B1, and CYP2E1 are among the most responsible for the biotransformation of chemicals, especially for the metabolic activation of pre-carcinogens. There is evidence of association between gene polymorphism and cancer susceptibility. Pathways of carcinogen metabolism are complex, and are mediated by activities...
Iranian Journal of Basic Medical Sciences
Article type: Short communication Objective(s): Cytochrome P-450 1A1 is an important enzyme in the first phase of the metabolism of some carcinogens such as polycyclic aromatic hydrocarbons (PAHs), as well as estrogen. The present study evaluates the existence of CYP1A1 polymorphism in a number of breast cancer samples. Materials and Methods: One hundred breast cancer patients and the same number of healthy controls were analyzed for the A2455G polymorphism of cytochrome P-450 1A1 by the polymerase chain reaction-restriction fragment length polymorphism technique. Results: Frequency of heterozygote genotype (A/G) indicated significant increase in case group (17%) compared to control group (7%) (OR=2.7; 95% CI=1.07-6.89; P-value=0.03). The related result of (A/A) genotype showed significantly decreased risk of breast cancer (OR=0.34; P-value=0.01). Higher frequency of heterozygotes was mainly observed among premenopausal breast cancer patients. Conclusion: Our results suggest that th...
Genetic polymorphisms of cytochrome P450-1A2 (CYP1A2) among Emiratis
PLOS ONE
Cytochrome P450 1A2 (CYP1A2) is one of the CYP450 mixed-function oxidase system that is of clinical importance due to the large number of drug interactions associated with its induction and inhibition. In addition, significant inter-individual differences in the elimination of drugs metabolized by CYP1A2 enzyme have been observed which are largely due to the highly polymorphic nature of CYP1A2 gene. However, there are limited studies on CYP1A2 phenotypes and CYP1A2 genotypes among Emiratis and thus this study was carried out to fill this gap. Five hundred and seventy six non-smoker Emirati subjects were asked to consume a soft drink containing caffeine (a non-toxic and reliable probe for predicting CYP1A2 phenotype) and then provide a buccal swab along with a spot urine sample. Taq-Man Real Time PCR was used to determine the CYP1A2 genotype of each individual. Phenotyping was carried out by analyzing the caffeine metabolites using High Performance Liquid Chromatography (HPLC) analysis. We found that 1.4%, 16.3% and 82.3% of the Emirati subjects were slow, intermediate and rapid CYP1A2 metabolizers, respectively. In addition, we found that 1.4% of the subjects were homozygote for derived alleles while 16.1% were heterozygote and 82.5% were homozygote for the ancestral allele. The genotype frequency of the ancestral allele, CYP1A2*1A/*1A, is the highest in this population, followed by CYP1A2 *1A/*1C and CYP1A2 *1A/*1K genotypes, with frequencies of 0.825, 0.102 and 0.058, respectively. The degree of phenotype/genotype concordance was equal to 81.6%. The CYP1A2*1C/*1C and CYP1A2*3/*3 genotypes showed significantly the lowest enzyme phenotypic activity. The frequency of slow activity CYP1A2 enzyme alleles is very low among Emiratis which correlates with the presence of low frequencies of derived alleles in CYP1A2 gene.