The development, validation and application of lung cancer risk biomarkers has been a major focus of this laboratory, ultimately impacting upon risk assessment, cancer prevention strategies and understanding of carcinogenic mechanisms. The biomarkers currently under study include genetic polymorphisms for carcinogen activation (CYP2D6, CYP2E1, CYP1A1, and NAT) and detoxification (GSTM1), protooncogenes (L- myc, HRAS1), and tumor suppressor genes (p53). The formation of human serum antibodies against p53 tumor suppressor gene protein and polycyclic aromatic hydrocarbon-DNA adducts (PAH-DNA adducts) also are being studied, the former representing p53 mutations and the latter representing exposure and determinants of adduct formation. This project has found that CYP1A1, NAT, GSTM1 and CYP2D6L and CYP2D6C genetic polymorphisms were not related to lung cancer risk in a Baltimore population but that CYP2D6L genotypes are predictive of debrisoquine phenotypes, where the minor allele is associated with increased metabolic capacity. CYP1A1 genetic polymorphisms are not related to each other in Americans, so the rare polymorphisms may be still be a risk factor but statistical power is limited and the more common polymorphisms cannot be used as surrogates. CYP2D6, CYP2E1 and GSTM1 null genotypes are associated with increased carcinogen-DNA levels in human lung, in vivo, thereby providing corroborating evidence for the importance of these genotypes in the carcinogenic process. Separately, cancer patients with serum anti-p53 antibodies have mutations in the p53 tumor suppressor gene and these antibodies have been found more commonly in African Americans than in Caucasians. Finally, in relation to wok cooking and lung cancer risk, cooking oils such as Chinese rapeseed and American Canola emit 1,3- butadiene, benzene and acrolein. These emissions can be reduced by cooking at lower temperatures or by the addition of antioxidants.
