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.
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).
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.
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.
This report defines CYP1A1 gene expression in normal lung tissue and primary pulmonary carcinoma tissue obtained at thoracotomy from 56 patients with lung cancer.
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.
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.
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.
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.
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.
Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population.
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.
A synergistic increase in susceptibility to lung cancer was found when combining genotyping of CYP1A1 and the Mu-class of glutathione S-transferase (GST1).
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).
The present study was set up to establish the frequencies of the polymorphic genotypes of CYP1A1 and GSTM1 in Sweden, to evaluate a possible increased incidence of the genotypes associated with higher lung cancer risks among Swedish lung cancer patients and to try to make a combined risk estimate for carriers of multiple risk alleles.