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 alterations in bronchial epithelium that antedate the development of lung carcinoma. The rising prevalence of marijuana and cocaine use among young adults in the United States prompted us to investigate whether similar molecular and histopathologic alterations occur in habitual smokers of marijuana and/or cocaine who may or may not also smoke tobacco.


METHODS
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 biopsy 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 proliferation], epidermal growth factor receptor, p53, Her-2/neu [also known as erbB-2 and ERBB2], globular actin, and abnormal DNA ploidy). Reported P values are two-sided.


RESULTS
Smokers of any one substance or of two or more substances exhibited more alterations than nonsmokers in five to nine of the 10 histopathologic parameters investigated (all P < .05), and they exhibited more molecular abnormalities than nonsmokers. Differences between smokers and nonsmokers were statistically significant (all P < or = .01) for Ki-67, epidermal growth factor receptor, globular actin, and DNA ploidy. There was general agreement between the presence of molecular abnormalities and histopathologic alterations; however, when disagreement occurred, the molecular abnormalities (e.g., Ki-67 and epidermal growth factor receptor) were more frequently altered (all P < or = .01).


CONCLUSIONS
These findings suggest that smoking marijuana and/or cocaine, like tobacco smoking, exerts field cancerization effects on bronchial epithelium, which may place smokers of these substances at increased risk for the subsequent development of lung cancer.
Department of Pathology, University of California, Los Angeles, USA. sbarsky@ucla.edu
S H
SH
Barsky
M D
MD
Roth
E C
EC
Kleerup
M
M
Simmons
D P
DP
Tashkin
D000199:Actins / Q000032:analysis; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001980:Bronchi / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology*; D001999:Bronchoscopy; D002283:Carcinoma, Bronchogenic / Q000737:chemistry / Q000209:etiology*; D016578:Crack Cocaine / Q000009:adverse effects*; D004848:Epithelium / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008385:Marijuana Smoking / Q000009:adverse effects* / Q000378:metabolism; D008875:Middle Aged; D011003:Ploidies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012306:Risk; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D000199:Actins; D014408:Biomarkers, Tumor; D016578:Crack Cocaine; D066246:ErbB Receptors; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53