The Impact of Cigarette Smoking on the Frequency of and Qualitative Differences in KRAS Mutations in Korean Patients with Lung Adenocarcinoma.
10.3349/ymj.2013.54.4.865
- Author:
Hye Ryun KIM
1
;
Jung Ryun AHN
;
Jin Gu LEE
;
Doo Hee BANG
;
Sang Jun HA
;
Yun Kyoung HONG
;
Sun Mi KIM
;
Ki Chang NAM
;
Sun Young RHA
;
Ross A SOO
;
Gregory J RIELY
;
Joo Hang KIM
;
Byoung Chul CHO
Author Information
1. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea. cbc1971@yuhs.ac
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
EGFR;
KRAS;
pulmonary adenocarcinoma;
cigarette smoking;
EGFR-tyrosine kinase inhibitors
- MeSH:
Adenocarcinoma/drug therapy/etiology/*genetics/pathology;
Adult;
Aged;
Aged, 80 and over;
Asian Continental Ancestry Group/genetics;
Female;
Humans;
Incidence;
Lung Neoplasms/drug therapy/etiology/*genetics/pathology;
Male;
Middle Aged;
*Mutation;
Mutation Rate;
Proportional Hazards Models;
Proto-Oncogene Proteins/*genetics;
Receptor, Epidermal Growth Factor/antagonists & inhibitors/genetics;
Smoking/adverse effects/*genetics;
Treatment Outcome;
ras Proteins/*genetics
- From:Yonsei Medical Journal
2013;54(4):865-874
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: This study was designed to determine the relationship of cigarette smoking to the frequency and qualitative differences among KRAS mutations in lung adenocarcinomas from Korean patients. MATERIALS AND METHODS: Detailed smoking histories were obtained from 200 consecutively enrolled patients with lung adenocarcinoma according to a standard protocol. EGFR (exons 18 to 21) and KRAS (codons 12/13) mutations were determined via direct-sequencing. RESULTS: The incidence of KRAS mutations was 8% (16 of 200) in patients with lung adenocarcinoma. KRAS mutations were found in 5.8% (7 of 120) of tumors from never-smokers, 15% (6 of 40) from former-smokers, and 7.5% (3 of 40) from current-smokers. The frequency of KRAS mutations did not differ significantly according to smoking history (p=0.435). Never-smokers were significantly more likely than former or current smokers to have a transition mutation (G-->A or C-->T) rather than a transversion mutation (G-->T or G-->C) that is known to be smoking-related (p=0.011). In a Cox regression model, the adjusted hazard ratios for the risk of progression with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were 0.24 (95% CI, 0.14-0.42; p<0.001) for the EGFR mutation and 1.27 (95% CI, 0.58-2.79; p=0.537) for the KRAS mutation. CONCLUSION: Cigarette smoking did not influence the frequency of KRAS mutations in lung adenocarcinomas in Korean patients, but influenced qualitative differences in the KRAS mutations.
