The data support the hypothesis that high AHH values may be characteristic of lung cancer patients but show that enzyme values determined from a single tissue, either PAMs or lymphocytes, may not be appropriate for showing whether high AHH inducibility is correlated with lung cancer.
Results reveal: a) an average interindividual variation in AHH activity of approximately 0.25 (coefficient of variation); range of activities among humans and baboon subjects of approximately 40-fold; c) both genetic and environmental determinants of interindividual variation, and d) high AHH activity in humans associated with primary lung cancer.
Recent clinical studies suggest a relationship between high AHH activity and lung cancer associated with cigarette smoking (Kouri, R.E., McKinney, C.E., Slomiany, D.J., Snodgrass, D.R., Wray, N.P., and McLemore, T.L.Cancer Res.42: 5030-5037, 1982).
These observations represent the first known demonstration of constitutive (non-induced) CYP1A1 gene expression in human cells and suggest altered regulation of the CYP1A1 gene in selected lung cancer cell lines.
In addition, an approximately 10-kilobase CYP1A1 RNA species, which was not detectable in normal lung tissue, was observed in five of ten (50%) of the lung cancers that expressed the CYP1A1 gene.(ABSTRACT TRUNCATED AT 250 WORDS)
Three examples of pharmacogenetic risk factors are discussed: the first two are p450 enzymes whose activity has been associated with susceptibility to lung cancer (debrisoquine hydroxylase, aryl hydrocarbon hydroxylase), and the last, N-acetyltransferase, a non-p450 enzyme, has been associated with bladder cancer susceptibility.
Human CYP1A1 (cytochrome P(1)450) gene: lack of association between the Msp I restriction fragment length polymorphism and incidence of lung cancer in a Norwegian population.
Epidemiologic evidence for the association of aryl hydrocarbon hydroxylase and lung cancer is presently problematic because of difficulties in the assay and subsequent confounding factors.
These results suggest that high pulmonary CYP1A1 expression (controlling in part carcinogen DNA-adduct formation) in tobacco smokers, appears to be associated with LC risk.
A recently described restriction fragment length polymorphism for the CYP1A1, which codes for the cytochrome P450 enzyme primarily responsible for the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons, has been found to be associated with lung cancer risk in a Japanese population.
It appears that interesting functionally linked interindividual differences in the CYP1A1 gene have been found and could be of importance in understanding differences in susceptibility to lung cancer.
This p53 polymorphism modulates risk to smoking-induced lung cancer independently of other genetic risk factors such as germ line polymorphism of CYP1A1 or GST1 genes.
The presence of the CYP1A1 Msp1 site-present allele, which was previously found to be associated with Japanese lung cancer risk, was statistically increased in African compared to Caucasian Americans (odds ratio, 2.9; 95% confidence interval, 1.2-2.7).
Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population.
A synergistic increase in susceptibility to lung cancer was found when combining genotyping of CYP1A1 and the Mu-class of glutathione S-transferase (GST1).
Cytochrome P450 1A1 (CYP1A1) activity is associated with increased susceptibility to lung cancer induced by polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BP).