Polymorphism in CYP1A1 and CYP2D6 genes: possible association with susceptibility to lung cancer.
Polymorphism of CYP2D6 gene encoding for debrisoquine hydroxylase was determined genotypically for 94 controls and 77 lung cancer patients using a polymerase chain reaction-based application. Both of the point mutations that give rise to deficient alleles of the CYP2D6 gene are detectable by this method. Out of the 94 healthy controls, 3 individuals (3.2%) had poor metabolizer (PM) genotypes, whereas no PM genotypes were detected in the lung cancer patient group. We observed no difference in the allelic frequencies for either homozygous extensive metabolizers (EMs) or heterozygous EMs between the lung cancer patients and the healthy controls. However, the absence of the poor metabolizer genotype (0/77) in the lung cancer patients is compatible with the hypothesis that there is an increased risk of lung cancer for individuals who are extensive metabolizers of debrisoquine. Another member of the cytochrome P450 gene superfamily that has attracted interest for its potential role in human pulmonary carcinogenesis is the CYP1A1 gene. In CYP1A1 gene studies, a polymorphic site assessable to MspI gives rise to two different hybridizable fragments in a Southern blot analysis (alleles C1 and C2, respectively). The C2C2 genotype has previously been associated with an increased risk of lung cancer. So far 74 lung cancer patients, 30 patients with lung diseases other than cancer, and 118 healthy controls have been studied for CYP1A1 gene polymorphism. No association between the MspI restriction fragment length polymorphism in the CYP1A1 gene and lung cancer susceptibility has been found.
Hirvonen
A
A
Department of Industrial Hygiene and Toxicology, Institute of Occupational Health, Helsinki, Finland.
Husgafvel-Pursiainen
K
K
Anttila
S
S
Karjalainen
A
A
Vainio
H
H
D000483:Alleles; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
D003577:Cytochrome P-450 Enzyme System