Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung

BACKGROUND. The majority of lung carcinoma cases occur in current or former smokers. K-ras gene mutations are common in lung adenocarcinoma and have b een associated with cigarette smoking, asbestos exposure, and female gender . METHODS. In the current study, the authors examined the contribution of cig arette smoking to K-ras gene mutations in patients with primary lung adenoc arcinoma. Smoking histories were obtained from 106 prospectively enrolled p atients with primary adenocarcinoma of the lung. RESULTS. K-ras mutations were detected in the primary tumor using an allele -specific ligation assay. Ninety-two of the 106 patients (87%) with lung ad enocarcinoma were smokers. Nonsmokers with this tumor were more likely to b e women (11 of 14; 79%), whereas the majority of smokers (57%) were men. K- ras mutations were detected in 40 of 106 tumors (38%) and were significant ly more common in smokers compared with nonsmokers (43% vs. 0%; P = 0.001). CONCLUSIONS. The results of the current study confirm and extend previous o bservations that smokers with adenocarcinoma of the lung are more likely to have K- ras mutant tumors compared with nonsmokers. The strong link betwee n cigarette smoking and K-ras mutations in adenocarcinoma of the lung suppo rts the role of specific tobacco carcinogens in the etiology of this malign ancy. (C) 2001 American Cancer Society.