A MOLECULAR EPIDEMIOLOGIC CASE-CONTROL STUDY OF LUNG-CANCER

Polycyclic aromatic hydrocarbon-DNA adducts were measured by ELISA in peripheral leukocytes from 119 non-small cell lung cancer patients and 98 controls at the Columbia-Presbyterian Medical Center, Thirty-one c ases had adduct measurements in leukocytes, lung tumor, and nontumor s pecimens collected at surgery, and 34 had paired leukocyte and tumor s pecimens, Information on smoking, diet, and occupational exposure was collected, After adjustment for age, gender, ethnicity, season, and sm oking, adducts in leukocytes were significantly higher in cases (P < 0 .01) than controls; the odds ratio was 7.7 (95% confidence interval = 1.7-34; P < 0.01), Adducts in leukocytes were increased significantly in smokers and ex-smokers compared to nonsmokers among cases and contr ols (separately and combined) after adjusting for age, gender, ethnici ty, and season (P < 0.05), The cases and controls differed in several respects: (a) adducts increased with the number of cigarettes smoked a mong the 51 cases who were current smokers (P = 0.05) but not among th e:current smokers in the controls; and (b) a seasonal variation in DNA binding, corresponding to that reported for aryl hydrocarbon hydroxyl ase inducibility, was observed in cases but not in controls, Among the cases, adducts in leukocytes were correlated more strongly with adduc ts in the lung tumor tissue than with those in nontumor lung tissue, T he results in leukocytes are consistent with a constitutional suscepti bility to lung cancer, which results in greater DNA damage from carcin ogens in cigarette smoke, They suggested that it may ultimately be pos sible to use biomarkers such as adducts to identify individuals who wo uld benefit most from early intervention.