Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied by use of PCR and XbaI and EcoRI restriction-fragment-length polymorphism whether mutations at the polymorphic CYP2D6 (debrisoquine hydroxylase) gene locus are associated with liver cancer. The frequency of CYP2D6 genes containing inactivating mutations was lower among 75 liver cancer patients than 200 healthy controls, and 40 cirrhotic subjects that did not develop liver cancer (frequency for carriers of two or more functional genes was 95% vs 74% vs 78%, respectively). Subjects who were homozygous for functional CYP2D6 genes appear to be at higher risk of developing primary liver cancer (odds ratio 6.40 [95% Cl] 2.4-17.5).
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PMID:CYP2D6 genes and risk of liver cancer. 789 30

Cytochrome P450 (CYP) enzymes catalyze the generation of reactive species capable of binding with cellular macromolecules, leading to acute and delayed toxicity. Since individual CYP forms differ markedly in their substrate preferences and regulation, the expression profiles of CYP in various cell types are important determinants in tissue-specific toxicity. The highest concentrations of most forms of CYP are found in liver, but they are also present in many extrahepatic organs. Liver is also a target organ in which CYP-mediated activation and toxic outcome have been most convincingly linked. Prime examples are paracetamol-induced hepatotoxicity and aflatoxin B1-associated hepatic cancer. In contrast to liver, most extrahepatic tissues are composed of multiple call types, which make experimental approaches difficult. Also the low abundance of individual forms is a challenge in the study of extrahepatic CYP-related toxicity. Recent years have witnessed the emergence of molecular biological techniques, e.g., reverse transcriptase-polymerase chain reactions, which facilitate the study of low abundant CYP forms in human tissues. Nevertheless, in the end we need definite information on the expression of activity, and for this purpose enzyme-specific substrates, reactions, and inhibitors and other methods to detect proteins and associated activities are needed. In humans, it is important to measure activities of specific enzymes in vivo. For this purpose, two approaches are currently available. Metabolism and/or elimination of enzyme-specific drugs can be employed. In cases in which genetic background determines the presence or absence of a specific enzyme, phenotyping and genotyping tests can be devised, e.g., for CYP2D6 (debrisoquine hydroxylation) polymorphism.
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PMID:Metabolic activation of toxins: tissue-specific expression and metabolism in target organs. 925 60

Human cytochrome P450 (CYP) enzymes play a key role in the metabolism of drugs and environmental chemicals. Several CYP enzymes metabolically activate procarcinogens to genotoxic intermediates. Phenotyping analyses revealed an association between CYP enzyme activity and the risk to develop several forms of cancer. Research carried out in the last decade demonstrated that several CYP enzymes are polymorphic due to single nucleotide polymorphisms, gene duplications and deletions. As genotyping procedures became available for most human CYP, an impressive number of association studies on CYP polymorphisms and cancer risk were conducted. Here we review the findings obtained in these studies regarding CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP3A7, CYP8A1 and CYP21 gene polymorphisms. Consistent evidences for association between CYP polymorphisms and lung, head and neck, and liver cancer were reported. Controversial findings suggest that colorectal and prostate cancers may be associated to CYP polymorphisms, whereas no evidences for a relevant association with breast or bladder cancers were reported. We summarize the available information related to the association of CYP polymorphisms with leukaemia, lymphomas and diverse types of cancer that were investigated only for some CYP genes, including brain, esophagus, stomach, pancreas, pituitary, cervical epithelium, melanoma, ovarian, kidney, anal and vulvar cancers. This review discusses on causes of heterogeneity in the proposed associations, controversial findings on cancer risk, and identifies topics that require further investigation. In addition, some recommendations on study design, in order to obtain more conclusive findings in further studies, are provided.
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PMID:Cytochrome P450 gene polymorphism and cancer. 1518 Apr 91

A study was conducted to determine the cytochrome (CYP) P450 enzymes responsible for the bioactivation of aflatoxin B1 (AFB1) into its epoxide form (AFBO) in duck liver microsomes. Six male and six female 6-week-old Pekin ducks were used. The biochemical toxicology strategies applied included the use of selective inhibitors, prototype substrate activity for specific human P450s, correlation between aflatoxin bioactivation and enzymatic activity of prototype substrates, and the expression of specific CYP450 enzymes using antibodies against human CYP450s. Enzymatic activity was detected for the duck orthologues CYP1A1/2, CYP2A6 and CYP3A4 but not for the CYP2D6 orthologue. Immunoreactive proteins for CYP1A1, CYP2A6 and CYP3A4 were also detected. Inhibition studies suggested that the duck turkey CYP2A6 orthologue and, to a lesser extent, the CYP1A1 orthologue are involved in the bioactivation of AFB1. Correlation studies, however, suggest that CYP3A4, CYP2A6 and CYP1A1/2 are all involved in AFBO formation. The finding that four CYP enzymes may be involved in AFB1 bioactivation in ducks could explain the high sensitivity of this species to AFB1. Further studies are needed to fully elucidate the phase I hepatic metabolism of AFB1 in ducks, the only poultry species that develops hepatic cancer from AFB1 exposure.
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PMID:The role of selected cytochrome P450 enzymes on the bioactivation of aflatoxin B1 by duck liver microsomes. 2070 84