Association between carcinogen-DNA adducts in white blood cells and lung cancer risk in the physicians health study

In this matched case-control study nested within the prospective Physicians ' Health Study, we evaluated whether DNA damage in blood samples collected at enrollment significantly predicted risk, consistent with our hypothesis that cases have greater biological susceptibility to polycyclic aromatic hy drocarbons and other aromatic tobacco carcinogens. The subjects were 89 cas es of primary lung cancer and 173 controls, all males, matched on smoking, age, and duration of follow-up. Aromatic-DNA adducts were measured in WBCs by the nuclease PI-enhanced P-32-postlabeling method that primarily detects smoking-related adducts. Among current smokers, but not former or nonsmoke rs, there was a significant increase in mean adduct levels of cases compare d with controls (11.04 versus 5.63, P = 0.03). "Healthy" current smokers wh o had elevated levels of aromatic DNA adducts in WBCs were approximately th ree times more likely to be diagnosed with lung cancer 1-13 years later tha n current smokers with lower adduct concentrations (odds ratio, 2.98; 95% c onfidence interval, 1.05-8.42, P = 0.04). We were not able to discern case- control differences in former smokers and nonsmokers. The findings are of i nterest because they suggest that individuals who become cases have greater biological susceptibility to tobacco carcinogens, a biological difference, which manifests most clearly while exposure is ongoing.