Lung cancer risk in relation to the CYP2C9 genetic polymorphism among Caucasians in Los Angeles County

London, Stephanie J.; Sullivan-Klose, Theresa H.; Daly, Ann K.; Idle, Jeffrey R.

doi:10.1097/00008571-199710000-00010

Cited by 34 publications

(10 citation statements)

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“…Only a few of the individual tobacco-related cancers have been investigated previously. In line with the results from Kaur-Knudsen et al, a statistical lack of association with lung cancer has been reported [73][74][75]. Bladder cancer has been associated with decreased risk for CYP2C9 combined carriers in one study [76], while another study examining only CYP2C9*3 found no association [77].…”

Section: Genetic Variation In Cyp2c9 and Risk Of Disease Cyp2c9 And Rsupporting

confidence: 69%

Cytochrome P450 1B1 and 2C9 Genotypes and Risk of Ischemic Vascular Disease, Cancer, and Chronic Obstructive Pulmonary Disease

Kaur-Knudsen

Bojesen²,

Nordestgaard³

2012

CVP

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The aim of this review is to summarize present knowledge of genetic variation in cytochrome P450 1B1 (CYP1B1) and 2C9 (CYP2C9) genes and risk of tobacco-related cancer, female cancer, chronic obstructive pulmonary disease and ischemic vascular disease. The CYP1B1 and CYP2C9 enzymes metabolize polycyclic aromatic hydrocarbons found in tobacco smoke and thereby generate disease-causing metabolites suggested to be important in tobacco-related diseases. Furthermore, CYP1B1 also metabolizes estrogen while CYP2C9 metabolizes arachidonic acid, both creating metabolites potentially important in risk of female cancer or ischemic vascular disease. Genetic variation in genes coding for CYP1B1 and CYP2C9 enzymes have shown altered enzyme activity affecting levels of metabolites and thus potentially risk of disease. So far, however, findings have been inconsistent. Recently, large studies on the association between genetic variation in CYP1B1 and CYP2C9 and risk of disease with considerable statistical power rebutted the hypotheses that these genetic variants affect risk of tobacco-related cancer, female cancer, chronic obstructive pulmonary disease and ischemic vascular disease.

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Section: Genetic Variation In Cyp2c9 and Risk Of Disease Cyp2c9 And Rsupporting

confidence: 69%

Cytochrome P450 1B1 and 2C9 Genotypes and Risk of Ischemic Vascular Disease, Cancer, and Chronic Obstructive Pulmonary Disease

Kaur-Knudsen

Bojesen²,

Nordestgaard³

2012

CVP

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“…In contrast to the in vitro activity data, comparison of the warfarin maintenance dose required for stable anticoagulation in patients who were homozygous wild‐type and Arg144Cys heterozygotes revealed that the average dose was 20% lower ( P =0.02) in the heterozygotes [138]. Since CYP2C9 is known to contribute to the metabolism of benzo[a]pyrene [26], a possible association between CYP2C9 genetic polymorphism and lung cancer risk has been addressed recently [139]. No association was found between lung cancer risk and expression of any of the CYP2C9 alleles.…”

Section: Factors Affecting Cyp2c9 Activitymentioning

confidence: 99%

Cytochrome P4502C9: an enzyme of major importance in human drug metabolism

Miners

Birkett

1998

Brit J Clinical Pharma

729

533

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Accumulating evidence indicates that CYP2C9 ranks amongst the most important drug metabolizing enzymes in humans. Substrates for CYP2C9 include fluoxetine, losartan, phenytoin, tolbutamide, torsemide, S-warfarin, and numerous NSAIDs. CYP2C9 activity in vivo is inducible by rifampicin. Evidence suggests that CYP2C9 substrates may also be induced variably by carbamazepine, ethanol and phenobarbitone. Apart from the mutual competitive inhibition which may occur between alternate substrates, numerous other drugs have been shown to inhibit CYP2C9 activity in vivo and/or in vitro. Clinically significant inhibition may occur with coadministration of amiodarone, fluconazole, phenylbutazone, sulphinpyrazone, sulphaphenazole and certain other sulphonamides. Polymorphisms in the coding region of the CYP2C9 gene produce variants at amino acid residues 144 (Arg144Cys) and 359 (Ile359Leu) of the CYP2C9 protein. Individuals homozygous for Leu359 have markedly diminished metabolic capacities for most CYP2C9 substrates, although the frequency of this allele is relatively low. Consistent with the modulation of enzyme activity by genetic and other factors, wide interindividual variability occurs in the elimination and/or dosage requirements of prototypic CYP2C9 substrates. Individualisation of dose is essential for those CYP2C9 substrates with a narrow therapeutic index.

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“…For example, increased expression of CYP2J2 in cancer tissues has been demonstrated in 101 out of 130 cancer patients in a recent study (Jiang et al 2005). CYP2C9 was found to be associated with increased risk of lung cancer (London et al 1996(London et al , 1997 and colorectal adenoma (Chan et al 2004). CYP2C8 and 2C9 were among the CYP450s suggested as risk factors for nasopharyngeal carcinoma, perhaps by playing a role in the bioactivation of pre-carcinogens (Jiang et al 2004).…”

Section: Introductionmentioning

confidence: 98%

Distribution of soluble epoxide hydrolase, cytochrome P450 2C8, 2C9 and 2J2 in human malignant neoplasms

2006

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Soluble epoxide hydrolase (sEH) is a bifunctional enzyme with a C-terminal epoxide hydrolase activity and an N-terminal phosphatase activity. Arachidonic acid epoxides, previously suggested to be involved in apoptosis, oncogenesis and cell proliferation, are generated by cytochrome P450 epoxygenases and are good substrates of the sEH C-terminal domain. In addition, the N-terminal phosphatase domain hydrolyzes isoprenoid mono- and pyrophosphates, which are involved in cell signaling and apoptosis. Here we provide a comprehensive analysis of the distribution of sEH, CYP2C8, 2C9 and 2J2 in human neoplastic tissues using tissue micro-arrays. The human neoplastic tissue micro-arrays provide a well-controlled side by side analysis of a wide array of neoplastic tissues and their surrounding normal tissue controls. Many of the neoplastic tissues showed altered expression of these enzymes as compared to normal tissues. Altered expression was not limited to the neoplastic tissues but also found in the surrounding non-neoplastic tissues. For example, sEH expression in renal and hepatic malignant neoplasms and surrounding non-neoplastic tissues was found to be significantly decreased, whereas expression was found to be increased in seminoma as compared to normal tissues. Our study warrants further investigation of the role of altered expression of these enzymes in neoplastic tissues.

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Lung cancer risk in relation to the CYP2C9 genetic polymorphism among Caucasians in Los Angeles County

Cited by 34 publications

References 0 publications

Cytochrome P450 1B1 and 2C9 Genotypes and Risk of Ischemic Vascular Disease, Cancer, and Chronic Obstructive Pulmonary Disease

Cytochrome P450 1B1 and 2C9 Genotypes and Risk of Ischemic Vascular Disease, Cancer, and Chronic Obstructive Pulmonary Disease

Cytochrome P4502C9: an enzyme of major importance in human drug metabolism

Distribution of soluble epoxide hydrolase, cytochrome P450 2C8, 2C9 and 2J2 in human malignant neoplasms

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