Metabolic phenotypes of retinoic acid and the risk of lung cancer

The metabolic activity of cytochrome P-450 enzymes has been associated with an increased risk of developing lung cancer. We found previously that all-trans retinoic acid is catabolized by these oxidative enzymes, and that an inhibitor of this system discriminated between two populations of lung canc...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1996-06, Vol.56 (12), p.2692-2696
Main Authors: RIGAS, J. R, MILLER, V. A, ZHANG, Z.-F, KLIMSTRA, D. S, TONG, W. P, KRIS, M. G, WARRELL, R. P
Format: Article
Language:English
Subjects:
Adenocarcinoma - etiology
Adenocarcinoma - metabolism
Analysis of Variance
Biological and medical sciences
Carcinoma, Large Cell - etiology
Carcinoma, Large Cell - metabolism
Carcinoma, Non-Small-Cell Lung - etiology
Carcinoma, Non-Small-Cell Lung - metabolism
Carcinoma, Squamous Cell - etiology
Carcinoma, Squamous Cell - metabolism
Case-Control Studies
Disease Susceptibility
Female
Hematologic and hematopoietic diseases
Humans
Keratolytic Agents - metabolism
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Lung Diseases, Obstructive - metabolism
Lung Neoplasms - etiology
Lung Neoplasms - metabolism
Male
Medical sciences
Middle Aged
Odds Ratio
Phenotype
Smoking - metabolism
Tretinoin - metabolism
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Summary:The metabolic activity of cytochrome P-450 enzymes has been associated with an increased risk of developing lung cancer. We found previously that all-trans retinoic acid is catabolized by these oxidative enzymes, and that an inhibitor of this system discriminated between two populations of lung cancer patients. We examined the association between this metabolic phenotype and the risk of lung cancer in 85 subjects. The area under the plasma concentration x time curve (AUC) was calculated after a single oral dose of all-trans retinoic acid (45 mg/m2). The mean AUC for patients who had either squamous or large cell carcinomas was significantly lower than that of patients with adenocarcinomas (P = 0.0001) or control subjects (P = 0.01). Individuals with an AUC < 250 ng x h/ml had a greater likelihood of having squamous or large cell carcinoma (odds ratio = 5.93). This study suggests that the "rapid" catabolism of all-trans retinoic acid is linked to an increased risk of squamous or large cell cancers of the lung.
ISSN:0008-5472
1538-7445