Cytochrome p450 1b1, a new keystone in gene-environment interactions related to human head and neck cancer?
Thier, Ricarda, Brüning, Thomas, Roos, Peter H., & Bolt, Hermann M. (2002) Cytochrome p450 1b1, a new keystone in gene-environment interactions related to human head and neck cancer? Archives of Toxicology, 76(5-6), pp. 249-256.
Alcohol consumption and tobacco smoking are major causes of head and neck cancers, and regional differences point to the importance of research into gene-environment interactions. Much interest has been focused on polymorphisms of CYP1A1 and of GSTM1 and GSTT1, but a number of studies have not demonstrated significant effects. This has mostly been ascribed to small sample sizes. In general, the impact of polymorphisms of metabolic enzymes appears inconsistent, with some reports of weak-to-moderate associations, and with others of no elevation of risks. The classical cytochrome P450 isoenzyme considered for metabolic activation of polycyclic aromatic hydrocarbons (PAH) is CYP1A1. A new member of the CYP1 family, CYP1B1, was cloned in 1994, currently representing the only member of the CYP1B subfamily. A number of single nucleotide polymorphisms of the CYP1B1 gene have been reported. The amino acid substitutions Val432Leu (CYP1B13) and Asn453Ser (CYP1B14), located in the heme binding domain of CYP1B1, appear as likely candidates to be linked with biological effects. CYP1B1 activates a wide range of PAH, aromatic and heterocyclic amines. Very recently, the CYP1B1 codon 432 polymorphism (CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squamous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has pointed to interactive effects. This provides new molecular evidence that tobacco smoke-specific compounds relevant to head and neck carcinogenesis are metabolically activated through CYP1B1 and is consistent with a major pathogenetic relevance of PAH as ingredients of tobacco smoke.
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|Item Type:||Journal Article|
|Keywords:||CYP1B1, Enzyme polymorphisms, Gene-environment interactions, Head and neck cancer, Laryngeal cancer, Tobacco smoking, alcohol, asphalt, coal tar, cytochrome P450 1B1, glutathione transferase, polycyclic aromatic hydrocarbon, tobacco smoke, carcinogen, cytochrome P 450 CYP1B1, cytochrome P-450 CYP1B1, unspecific monooxygenase, xenobiotic agent, alcohol consumption, cancer risk, catalysis, enzyme specificity, gene mutation, genetic polymorphism, genotype, head and neck carcinoma, human, nonhuman, priority journal, review, smoking, amino acid substitution, enzymology, genetics, head and neck tumor, metabolism, Aryl Hydrocarbon Hydroxylases, Carcinogens, Environmental, Head and Neck Neoplasms, Polymorphism (Genetics), Substrate Specificity, Support, Non-U.S. Gov't, Xenobiotics, Humans, Polymorphism, Genetic, Nicotiana tabacum|
|Divisions:||Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
|Copyright Owner:||Copyright 2002 Springer-Verlag|
|Deposited On:||16 Oct 2014 04:40|
|Last Modified:||16 Oct 2014 04:43|
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