A comparison between the localization of lung tumors in uranium miners and in nonminers from 1947 to 1991.

BACKGROUND: Lung cancer was noted to be increased in cigarette smoking miners and nonminers. Carcinogen particulates deposit differentially in the central, middle, and peripheral zones of the bronchial tree depending on the size of the particle. The object of this study was to evaluate the incidence of tumors; their cell types; and the relationship of particulate size to their position in the bronchial tree. METHODS: Tumor position in the bronchial tree was studied for a cohort of 467 uranium miners and 311 nonminers with lung cancer. RESULTS: An examination of all histologic subtypes showed that the proportion of lung cancers in the central zone was significantly greater in miners than in nonminers presumably due to the deposition of radon decay products attached to the silica dust particles. The higher percentage of central tumors in the miners was primarily due to the distribution of a greater proportion of squamous cell and small-cell tumors. The ratio of 0.75 for the central to middle and peripheral location for adenocarcinomas was much lower than for squamous cell and small-cell carcinomas with ratios of 1.4 and 7.3, respectively. In the mining cohort, there were ten times as many small-cell tumors in the central area as in the middle and peripheral regions, whereas, for the nonminers there were only five times as as many centrally located small-cell tumors as middle and peripheral (chi square is 7.0 degrees, P < 0.01). These data suggest that radon may be deposited preferentially to the central region of the lungs in uranium miners. CONCLUSIONS: Based on our observations of the differential positions of lung tumors in the bronchial tree for miners and nonminers and previous studies by others regarding size-dependent deposition of particulates in the bronchial tree, it is concluded that inhaled dust, radon, and cigarette smoke combine to form large particulates that deposit in the central bronchial tree. Filtered cigarette smoke or other small carcinogens from smaller particulates that deposit more peripherally.

p53 mutation hotspot in radon-associated lung cancer.

Mutations in gene p53 are the most common defects in lung cancer and may be a pathway through which environmental carcinogens initiate cancer. We investigated p53 mutations in lung cancers from uranium miners with high radon exposure. 16 (31%) of 52 large-cell and squamous-cell cancers from miners contained the same AGG to ATG transversion at codon 249, including cancers from 3 or 5 miners who had never smoked. This specific mutation has been reported in only 1 of 241 published p53 mutations from lung cancers. The codon 249 mutation may be a marker for radon-induced lung cancer.