Yonsei Med J.
2013 Jul;54(4):865-874. 10.3349/ymj.2013.54.4.865.
The Impact of Cigarette Smoking on the Frequency of and Qualitative Differences in KRAS Mutations in Korean Patients with Lung Adenocarcinoma
- Affiliations
-
- 1Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea. cbc1971@yuhs.ac
- 2Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
- 3Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, Korea.
- 4Department of Chemistry, College of Science, Yonsei University, Seoul, Korea.
- 5Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul, Korea.
- 6JE UK Institute for Cancer Research, Gumi, Korea.
- 7Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea.
- 8Institute for Cancer Research, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
- 9Department of Medical Engineering, Yonsei University College of Medicine, Seoul, Korea.
- 10Clinical Trials Centers for Medical Devices, Yonsei University Health System, Seoul, Korea.
- 11Department of Hematology-Oncology, National University Cancer Institute, National University Health System, Singapore.
- 12Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, New York, NY, USA.
- KMID: 2158219
- DOI: http://doi.org/10.3349/ymj.2013.54.4.865
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.
MeSH Terms
-
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
Proto-Oncogene Proteins
Receptor, Epidermal Growth Factor
ras Proteins
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