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

Abstract

BACKGROUND: The majority of lung carcinoma cases occur in current or former smokers. K-ras gene mutations are common in lung adenocarcinoma and have been associated with cigarette smoking, asbestos exposure, and female gender. METHODS: In the current study, the authors examined the contribution of cigarette smoking to K-ras gene mutations in patients with primary lung adenocarcinoma. Smoking histories were obtained from 106 prospectively enrolled patients 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 adenocarcinoma were smokers. Nonsmokers with this tumor were more likely to be 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 significantly more common in smokers compared with nonsmokers (43% vs. 0%; P = 0.001). CONCLUSIONS: The results of the current study confirm and extend previous observations that smokers with adenocarcinoma of the lung are more likely to have K-ras mutant tumors compared with nonsmokers. The strong link between cigarette smoking and K-ras mutations in adenocarcinoma of the lung supports the role of specific tobacco carcinogens in the etiology of this malignancy.