Individuals at high risk for lung cancer have airway epithelial cells with chromosome aberrations frequently found in lung tumor cells.
Identification of individuals at greatest risk of developing lung cancer could enhance the efficacy of intervention modalities, thereby greatly reducing mortality from this disease. One strategy for identifying these people is to establish molecular markers which reflect the severity of their cancerization field. Thus, investigations were initiated to determine of cells with chromosome aberrations frequently exhibited by lung tumor cells, i.e., trisomy 7, trisomy 20, and deletion of 9p23, are prevalent within the uninvolved airways of cancer patients. As a result, cells containing these aberrations were consistently found at significantly elevated levels by using fluorescence in situ hybridization (FISH). In contrast, cells collected from non-smokers who had never smoked were normal by this assay. The next objective was to determine of cells exhibiting these alterations are also present in upper airways of exposed, but cancer-free smokers and ex-uranium miners. The results showed that, although only a subset of these people will develop lung cancer in their lifetimes, they universally harbor increased numbers of abnormal cells within their airway epithelium. However, the number of sites with multiple verities of abnormal cells tended to be fewer compared with the cancer patients. Thus, quantifying cells with molecular alterations within the cancerization field of a smoker may delineate those with a lesser grade of damage, and these individuals may be at a lesser risk of developing disease. However, differences in the extent of genetic damage afforded by these assays may not clearly define individuals with pending disease, and additional molecular assays must be devised.
Lechner
J F
JF
Lovelace Respiratory Research Institute, Albuquerque, NM 87185, USA. jlechner@lrri.org
Neft
R E
RE
Gilliland
F D
FD
Crowell
R E
RE
Auckley
D H
DH
Temes
R T
RT
Belinsky
S A
SA
D001980:Bronchi / Q000473:pathology*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004847:Epithelial Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D014314:Trisomy; D014407:Tumor Cells, Cultured