title: Lung cancer and past occupational exposure to asbestos. Role of p53 and K-ras mutations.
abstract: Studies on somatic mutations in lung cancers associated with cigarette smoking and asbestos exposure are few. We investigated prevalence of mutations in the p53 and K-ras genes in lung tumors from smokers with and without asbestos exposure at work. For K-ras mutations, the study was an extension of an earlier analysis. Nearly all of the 105 consecutive patients examined were smokers and had non-small-cell carcinoma of the lung with squamous-cell carcinoma or adenocarcinoma histology. Exposure to asbestos was estimated by pulmonary fiber counts and occupational histories. A pulmonary burden of >/= 1 x 10(6) asbestos fibers per gram of lung tissue, indicating work-related exposure, was found in 32% of the patients for whom fiber-analysis data were available (33 of 102 patients, all men). The statistical analysis showed pulmonary fiber count as the only significant predictor of adenocarcinoma histology, in contrast to squamous-cell carcinoma (smoking-adjusted odds ratio [OR] 3.0, 95% confidence interval [CI] 1.1 to 8.5). The frequency of p53 mutations was 39% (13 of 33) among the asbestos-exposed cases, as compared with 54% (29 of 54) among the nonexposed cases; the difference was not significant, however. In male ever-smokers, a long duration of smoking was associated with p53 mutation (OR 3.2, 95% CI 1.2 to 8.8). In adenocarcinoma, p53 mutations were less prevalent (10 of 30, 33%) as compared with squamous-cell carcinoma (28 of 46, 61%; P = 0.02), whereas a strong and significant association was found between adenocarcinoma and K-ras mutation (OR 37, 95% CI 5.8 to 232, adjusted for smoking and asbestos exposure). Asbestos exposure alone was not significantly associated with increased occurrence of K-ras mutations. In conclusion, the results may primarily reflect the observed excess of adenocarcinoma in the asbestos- exposed patients, and hence the decrease in p53 mutations and increase in K-ras mutations.
authors: Departments of Industrial Hygiene and Toxicology, Epidemiology and Biostatistics, and Occupational Medicine, Finnish Institute of Occupational Health, Helsinki, Finland. Kirsti.Husgafvel-Pursiainen@occuphealth.fi
authors: K
authors: K
authors: Husgafvel-Pursiainen
authors: A
authors: A
authors: Karjalainen
authors: A
authors: A
authors: Kannio
authors: S
authors: S
authors: Anttila
authors: T
authors: T
authors: Partanen
authors: A
authors: A
authors: Ojajärvi
authors: H
authors: H
authors: Vainio
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D017668:Age of Onset; D000704:Analysis of Variance; D001194:Asbestos; D002289:Carcinoma, Non-Small-Cell Lung / Q000209:etiology* / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics / Q000473:pathology; D005260:Female; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008168:Lung / Q000473:pathology / Q000648:ultrastructure; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D009154:Mutation; D016273:Occupational Exposure; D012044:Regression Analysis; D012907:Smoking / Q000235:genetics
chemical_list: D001194:Asbestos