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CYP2D6 genotype and lung cancer risk according to histologic type and tobacco exposure. 1995

I Stücker, and J Cosme, and P Laurent, and S Cenée, and P Beaune, and J Bignon, and A Depierre, and B Milleron, and D Hémon
Unité de Recherches Epidémiologiques et Statistiques sur l'Environnement et la Santé, INSERM U 170, Villejiuf, France.

Polymorphism for CYP2D6 was determined genetically as part of a hospital-based case-control study. The cases were males with a histologically confirmed lung cancer diagnosis, < 75 years old, and no previous cancer diagnosis. Male controls were matched for age, hospital and residence area. This study includes 301 cases and 310 controls. A DNA bank was established for 547 patients (89.5%), and genotypes for CYP2D6 were differentiated by the Heim and Meyer method for the DNA samples of 249 cases and 271 controls. Among the cases, the frequencies of homozygous for the wild-type (EM), heterozygous (HEM) and homozygous for the mutant alleles (PM) were 62%, 32% and 7%; among the controls: 57%, 37% and 6%. Using EM as the reference, and adjusting for age, hospital and residence, we estimated the odds ratios for the HEM group and the PM group at 0.8 (95% CI [0.5-1.2]) and 1.1 (95% CI [0.5-2.4]) respectively. The PM frequency among the cases of adenocarcinoma was twice as high as among the controls (OR = 1.8, 95% CI [0.7-4.9]). This result was not observed among squamous and small cell carcinoma (OR = 0.7, 95% CI [0.3-1.8]). Twelve different case-control studies on CYP2D6 and lung cancer have so far been performed; the ORs they estimate range from 0.1 to 2.0, with a median value of approximately 0.6. This result lends some support to the hypothesis that belonging to the PM group is associated with a slight protective effect against lung cancer, but does not take into account the possibility that results may vary according to histologic type. In this context, the suggestion of a positive relationship between CYP2D6 and adenocarcinoma seems to us to merit investigation.

UI MeSH Term Description Entries
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D012150 Polymorphism, Restriction Fragment Length Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment. RFLP,Restriction Fragment Length Polymorphism,RFLPs,Restriction Fragment Length Polymorphisms
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006899 Mixed Function Oxygenases Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation. Hydroxylase,Hydroxylases,Mixed Function Oxidase,Mixed Function Oxygenase,Monooxygenase,Monooxygenases,Mixed Function Oxidases,Function Oxidase, Mixed,Function Oxygenase, Mixed,Oxidase, Mixed Function,Oxidases, Mixed Function,Oxygenase, Mixed Function,Oxygenases, Mixed Function
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly

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