ASSOCIATIONS BETWEEN BOTH GENETIC AND ENVIRONMENTAL BIOMARKERS AND LUNG-CANCER - EVIDENCE OF A GREATER RISK OF LUNG-CANCER IN WOMEN SMOKERS

This molecular epidemiologic case-control study of lung cancer incorpo rated three complementary biomarkers: the glutathione S-transferase M1 (GSTM1) null genotype, a potential marker of susceptibility, and poly cyclic aromatic hydrocarbon-DNA adducts (PAH-DNA) and sister chromatid exchanges (SCE), both indicators of environmentally induced genetic d amage. Associations between biomarkers and lung cancer were investigat ed, as were possible gene-environment interactions between the GSTM1 n ull genotype and tobacco smoke exposure. Subjects included 136 primary non-small cell lung cancer surgical patients and 115 controls at the Columbia Presbyterian Medical Center. Questionnaire and Tumor Registry data, pre-treatment blood samples and biomarker measurements on blood were obtained. Overall, GSTM1 null genotype was significantly associa ted with lung cancer [odds ratio (OR) = 2.04, 95% confidence interval (CI) = 1.13-3.68]. ORs for GSTM1 and lung cancer were significant in f emales (2.50, 1.09-5.72) and smokers (2.25, 1.11-4.54) and not signifi cant in males (1.4, 0.58-3.38) and nonsmokers (0.88, 0.18-4.33). Howev er, ORs for males versus females and smokers versus non-smokers did no t differ significantly. The OR for GSTM1 and lung cancer in female smo kers was 3.03 (1.09-8.40), compared with 1.42 (0.53-4.06) in male smok ers. In contrast to PAH-DNA adducts in leukocytes, SCE did not differ between cases and controls. Neither biomarker differed significantly b etween the two GSTM1 genotypes. The combined effect of elevated PAH-DN A adducts and GSTM1 genotype on case-control status (16.19, 1.2-115) a ppeared multiplicative. Results suggest that the effect of the GSTM1 n ull genotype is greatest in female smokers, which is consistent with o ther evidence that indicates that women are at higher risk of lung can cer than males, given equal smoking. Persons with both the GSTM1 delet ion and elevated PAH-DNA adducts may represent a sensitive subpopulati on with respect to carcinogens in tobacco smoke and other environmenta l media.