In a case-control study, we tested the hypothesis that the genetically determined ability to metabolize
debrisoquine is related to risk of
lung cancer. Overall, individuals who were extensive metabolizers of
debrisoquine were at significantly greater risk of
lung cancer than those who were poor or intermediate metabolizers (odds ratio = 6.1; 95% confidence interval = 2.2-17.1). In this study, case patients had
lung cancer, and control subjects had either
chronic obstructive pulmonary disease or
cancers other than
lung cancer. Results were adjusted for age, race,
asbestos exposure, and smoking. Both black and white individuals who were extensive metabolizers of
debrisoquine were at significantly increased risk after similar adjustment (for blacks, odds ratio = 4.5, 95% confidence interval = 1.1-18.1; for whites, odds ratio = 10.2, 95% confidence interval = 2.0-51.4). Significantly increased risk of
lung cancer was also present for individuals who were extensive metabolizers when subjects with
chronic obstructive pulmonary disease or other
cancers were considered separately. These data confirm that the ability to metabolize
debrisoquine is a major determinant of susceptibility to
lung cancer. Evaluation of the marker in other case-control settings, further exploration of racial differences, and the prospective evaluation of this marker in subgroups at high risk of
lung cancer are areas worthy of further study.