Bronchogenic carcinoma is closely associated with cigarette smoking although additional environmental or individual factors might regulate a person's susceptibility to that disease. To further define such risk factors, the prevalence of the genetic
debrisoquine 4-hydroxylation deficiency was determined before therapeutic intervention in 270
lung cancer patients. Nineteen homozygous carriers of this defect (poor metabolizers) were found (7.0%, 95% confidence limits 4.3%-10.8%), a number being lower than 30 out of 270 reference patients (11.1%, 95% confidence limits 7.6%-15.5%). The odds ratio of 0.61 was of marginal statistical significance (P = 0.067). Subdividing the collective according to histology revealed a trend towards underrepresentation of poor metabolizers especially among patients with
adenocarcinoma (1 out of 37, P = 0.086) and among young patients not older than 50 years (none out of 32, P = 0.028). All poor metabolizers (PMs) in the
cancer group were smokers. In 18 patients the phenotype assignment was confirmed by a second test several weeks after surgical or other treatment. In 220 of the
lung cancer patients the N-
acetyltransferase polymorphism was evaluated by means of the molar ratio of
5-acetylamino-6-formylamino-3-methyluracil and
1-methylxanthine in urine after ingestion of
caffeine (
coffee). There were 111 (50.5%) slow acetylators and 109 (49.5%) fast acetylators. A statistically significant clustering of either phenotype after stratification according to histology, or
debrisoquine hydroxilator status was lacking. Moreover, there was no difference in the ratio of both phenotypes as compared to the reference collective of 245 patients (53.5% slow and 46.5% fast acetylators). As a third genetic host factor the AB0
blood group frequencies were evaluated in 263
lung cancer patients. The frequency ratio of A/O was significantly higher as compared to 41,423 blood donors (odds ratio 1.37, 95% confidence limits 1.02-1.84, P less than 0.05). A/O tended to be especially high in young patients not older than 50 years. The ratio B/O in bronchial
cancer was significantly higher than expected. The results suggest that the
debrisoquine hydroxilator status might have an impact on an individual's susceptibility to
lung cancer. This association is either a weak one and/or is restricted to certain histological
cancer types or to patients with certain characteristics. The acetylator phenotype could not be established as a risk factor, whereas AB0
blood groups seem to influence
lung cancer susceptibility.