title: Interaction between smoking and asbestos in human lung adenocarcinoma: role of K-ras mutations.
abstract: To investigate the role of tobacco smoking and asbestos fibers in the etiology of human lung cancer, we examined the activating point mutations in the K-ras oncogene in DNA samples from 49 patients. Mutations were found more often in tissue from adenocarcinomas (12/21) than in tissue from tumors other than nonadenocarcinomas of the lung (3/28). Among the adenocarcinoma patients, asbestos exposure was predictive of K-ras mutation (odds ratio, 4.9; 95% confidence interval, 0.7-34.3); in patients with other types of lung cancer, the relation appeared to be an inverse one, but the numbers were small. The proportion of heavy smokers (over 50 pack-years) was 60% among people with K-ras mutations and 35% among the K-ras-negative subjects, suggesting that smoking causes K-ras mutations. If mutations in K-ras genes are caused by smoking, asbestos would act as a promoting agent by conferring selective growth conditions for clonal expansion on these mutated cells. Asbestos may favor recruitment of (initiated) K-ras mutation-positive cells in the multistage process of carcinogenesis by stimulating cellular growth.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: H
authors.initials: H
authors.lastname: Vainio
authors.forename: K
authors.initials: K
authors.lastname: Husgafvel-Pursiainen
authors.forename: S
authors.initials: S
authors.lastname: Anttila
authors.forename: A
authors.initials: A
authors.lastname: Karjalainen
authors.forename: P
authors.initials: P
authors.lastname: Hackman
authors.forename: T
authors.initials: T
authors.lastname: Partanen
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology* / Q000235:genetics; D000368:Aged; D001194:Asbestos / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012907:Smoking / Q000009:adverse effects*
chemical_list: D001194:Asbestos