title: Differences inEGFRandKRASmutation spectra in lung adenocarcinoma of never and heavy smokers.
abstract: Epidermal growth factor receptor (EGFR) mutations are common in lung adenocarcinomas of never smokers, whileKRASmutations are more frequent among heavy smokers. Different clinicopathological and biological characteristics may, therefore, exist in lung adenocarcinoma according to smoking status. In the present study, a retrospective review was performed using 521 patients with surgically resected lung adenocarcinomas. The clinicopathological factors of age, gender, pathological tumor size, nodal status, lymphatic permeation and blood vessel invasion and theEGFRandKRASmutation spectra were compared between never and heavy smokers.EGFRmutations were detected in 233 (45%) patients, whileKRASmutations were detected in 56 (11%) patients.EGFR-mutated adenocarcinomas had a higher prevalence of females in the never smokers compared with the heavy smokers (P<0.001).KRAS-mutated adenocarcinomas had a higher prevalence of females (P<0.001) and showed less frequent vascular invasion (P=0.018) in the never smokers compared with the heavy smokers. MinorEGFRmutations, excluding exon 21 L858R and exon 19 deletions, were more common in heavy smokers than never smokers (P=0.055).KRASG to A transition was more common in never smokers, whileKRASG to T and G to C transversions were more common in heavy smokers (P=0.036). The clinicopathological characteristics and the spectra of theEGFRandKRASmutations in lung adenocarcinoma were different between the never and heavy smokers. Further large-scale studies are required to evaluate the efficacy of molecular targeting agents with consideration to specificEGFRandKRASmutations.
authors.affiliation: Department of General Thoracic Surgery, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8431, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Takamochi
authors.forename: Shiaki
authors.initials: S
authors.lastname: Oh
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
keywords: KRAS; adenocarcinoma; epidermal growth factor receptor; lung cancer; mutation; smoking