DEBRISOQUINE METABOLISM AND LUNG-CANCER RISK

Previous reports of the association between the debrisoquine metabolic polymorphism and lung cancer risk have been conflicting. We examined the hypothesis that the genetically determined ability to metabolize d ebrisoquine identifies individuals at increased risk for lung cancer i n a study designed to address some of the methodological criticisms of previous studies. A case-control study of 335 incident Caucasian lung cancer patients and 373 controls matched for age, race, sex, and hosp ital, was conducted at the National Naval Medical Center (Bethesda, MD ) and at the Laval Hospital (Sainte-Foy, Quebec, Canada). Debrisoquine metabolic phenotype was determined by debrisoquine administration and analysis of debrisoquine and 4-hydroxydebrisoquine in the subsequent 8-h urine collected. Stratified and logistic regression analyses were used to evaluate the association between extensive or intermediate deb risoquine metabolism and lung cancer risk. We found no increased risk among extensive or intermediate metabolizers (odds ratio, 0.6; 95% con fidence interval, 0.3-1.2). The lack of an association was not confoun ded by control diagnoses, medications used within 1 month of debrisoqu ine administration, smoking, stage, or histology of lung cancer. No re lationship was found among either heavy smokers or light and nonsmoker s. Our results do not support the role of debrisoquine metabolism as a marker for lung cancer risk. While the concept that polymorphisms of metabolism may account for differential susceptibility to lung cancer is sound, debrisoquine metabolic phenotype was not associated with lun g cancer risk in these data.