Genetic Susceptibility to Squamous Cell Carcinoma of the Lung in Relation to Cigarette Smoking Dose1

Cytochrome P450IÕ1 is responsible for the metabolic activation of benzo(a)pyrene in cigarette smoke; an association of lung cancer with DNA polymorphisms of P450IA1 gene was shown in our previous study. In this paper, we investigated the interindividual difference of geneti cally determined susceptibility to squamous cell carcinoma of the lung in relation to cigarette smoking dose. We tirsi compared the total amounts of cigarettes consumed over the lifetime of patients and showed that the patients with a "susceptible" P450IA1 gene genotype contracted carci noma after fewer cigarettes (mean ±SD, 31.3 ±12.8 x IO4cigarettes (n = 12)] than those with other genotypes [42.5 ±18.2 x HI4(n = 33)], with a statistical significance of P < 0.05. Next, we carried out a casecontrol study to estimate the odds ratios of susceptible to nonsusceptible individuals in relation to the cumulated cigarette dose. We thus showed that the individuals with the susceptible genotype were at remarkably high risk with an odds ratio of 7.31 (95% confidence interval, 2.13 to 25.12) at a low dose level of cigarette smoking and that the difference in susceptibility between genotypes was reduced at high dose levels.