HISTOPATHOLOGIC AND MOLECULAR ALTERATIONS IN BRONCHIAL EPITHELIUM IN HABITUAL SMOKERS OF MARIJUANA, COCAINE, AND OR TOBACCO/

Background: Tobacco smoking has been observed to cause molecular alter ations in bronchial epithelium that antedate the development of lung c arcinoma, The rising prevalence of marijuana and cocaine use among you ng adults in the United States prompted us to investigate whether simi lar molecular and histopathologic alterations occur in habitual smoker s of marijuana and/or cocaine who may or may not also smoke tobacco, M ethods: Bronchoscopy was performed in 104 healthy volunteer subjects, including 28 nonsmokers and 76 smokers of one or more of the following substances: marijuana, tobacco, and/or cocaine. Bronchial mucosa biop sy specimens and brushings were analyzed for histopathologic changes, for immunohistopathologic expression of intermediate or surrogate end- point markers that are linked to an increased risk of cancer (Ki-67 [a marker of cell proliferations], epidermal growth factor receptor, p53 , Her-2/neu [also known as erbB-2 and ERBB2], globular actin, and abno rmal DNA ploidy). Reported P values are two-sided. Results: Smokers of any one substance or of two or more substances exhibited more alterat ions than nonsmokers in five to nine of the PO histopathologic paramet ers investigated (all P<.05), and they exhibited more molecular abnorm alities than nonsmokers. Differences between smokers and nonsmokers we re statistically significant tall P less than or equal to.01) for Ki-6 7, epidermal growth factor receptor, globular actin, and DNA ploidy. T here was general agreement between the presence of molecular abnormali ties and histopathologic alterations; however, when disagreement occur red, the molecular abnormalities (e,g,, Ki-67 and epidermal growth fac tor receptor) were more frequently altered (all P less than or equal t o.01). Conclusions: These findings suggest that smoking marijuana and/ or cocaine, like tobacco smoking, exerts field cancerization effects o n bronchial epithelium, which may place smokers of these substances at increased risk for the subsequent development of lung cancer.