Lung Cancer and Past Occupational Exposure to Asbestos

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.

Aberrant p16 promoter methylation in smokers and former smokers with nonsmall cell lung cancer

“…26 For 58 of the cases, a specimen of nonmalignant peripheral lung tissue was also available for investigation. In addition, leukocyte DNAs from cancer patients (n ϭ 15) were examined.…”

“…Data on occupational asbestos exposure were available for 61 patient, with 22 cases exposed to asbestos at work. 26 …”

Molecular Profiling in Non–Small Cell Lung Cancer: A Step Toward Personalized Medicine

“…43,44 KRAS mutations are shown to be associated with smoking history and asbestos exposure. 37,45 Incidentally, KRAS mutations are more prevalent in women than men. Nelson et al 37 reported that this association was statistically significant after adjustment for cigarette smoking and asbestos exposure, implicating a possible role of estrogen in either initiating or selectively targeting KRAS mutation sites in pulmonary adenocarcinoma.…”

Physicochemical Properties and Factors that Induce Asbestos-Related Respiratory Disease

“…In the genetic abnormality of asbestos-related lung cancer, mutations of the k-ras and TP53 (p53) have been reported [38][39][40][41][42][43][44][45][46][47][48] . K-ras mutation is an oncogene that plays an important role in the signal transduction of the epidermal growth factor receptor (EGFR).…”