A SPECIFIC AFRICAN-AMERICAN CYP1A1 POLYMORPHISM IS ASSOCIATED WITH ADENOCARCINOMA OF THE LUNG

A case-control study on lung cancer in African-Americans has been cond ucted to assess whether a novel African-American-specific polymorphism in the CYP1A1 gene increases the susceptibility to tobacco-related lu ng cancer. The prevalence of the AA RFLP was 17.1% in the DNA extracte d from archived tissue blocks from 76 incident cases of lung cancer, a nd was 16.3% in peripheral blood lymphocyte DNA of 123 healthy African -American volunteers recruited from a community in the eastern United States. The analysis by histological type showed an association betwee n adenocarcinoma (AC) of the lung and the AA RFLP (odds ratio, 2.6; 95 % confidence interval, 1.1-6.3). One homozygous variant subject was pr esent among the AC cases. The risk of AC in subjects who both smoke an d carry the AA RFLP was more than double, in comparison to subjects wh o only smoke (relative interaction magnitude under the additive model, 24%). The mean value of pack-year in AC with the polymorphism was 5.0 +/- 2.5 and in AC without the polymorphism was 37.2 +/- 6.5 (P < 0.05 ). Our data suggest that a selective association exists between the AA polymorphism and adenocarcinoma of the lung and that a lower dose of tobacco is sufficient to exert carcinogenic effects on the adenomatous tissue of subjects carrying the AA polymorphism.