Lung cancer and past occupational exposure to asbestos - Role of p53 and K-ras mutations

Studies on somatic mutations in lung cancers associated with cigarette smok ing 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 asb estos exposure at work. For K-ras mutations, the study was an extension of an earlier analysis. Nearly all of the 105 consecutive patients examined we re smokers and had non-small-cell carcinoma of the lung with squamous-cell carcinoma or adenocarcinoma histology. Exposure to asbestos was estimated b y pulmonary fiber counts and occupational histories. A pulmonary burden of greater than or equal to 1 x 10(6) asbestos fibers per gram of lung tissue, indicating work-related exposure, was found in 32% of the patients for who m fiber-analysis data were available (33 of 102 patients, all men). The sta tistical analysis showed pulmonary fiber count as the only significant pred ictor 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-e xposed cases, as compared with 54% (29 of 54) among the nonexposed cases; t he difference was not significant, however. In male ever-smokers, a long du ration 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%) a s 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 in creased occurrence of K-ras mutations. In conclusion, the results may prima rily reflect the observed excess of adenocarcinoma in the asbestos-exposed patients, and hence the decrease in p53 mutations and increase in K-ras mut ations.