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.
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

Due to the advanced diagnostic technique and better understanding for multiple primary lung cancers (MPLC), the increasing incidence of MPLC has been reported. Very often, MPLC are misdiagnosed as metastasis because of lacking efficient molecular biomarkers for prediction and diagnosis. Studies on the molecular mechanism for tumorgenesis and progression of MPLC may therefore facilitate the discovery of biomarkers for disease diagnosis and prognosis, so that an individual and rational treatment can be achieved. We tried to further our understanding and improve the diagnostic skill for MPLC by reviewing the current status and the latest advancement of molecular markers related to MPLC.
Adenocarcinoma ; pathology ; Biomarkers, Tumor ; analysis ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; radiotherapy ; Carcinoma, Small Cell ; pathology ; Carcinoma, Squamous Cell ; pathology ; Chromosome Deletion ; DNA Damage ; Genes, Tumor Suppressor ; Humans ; Incidence ; Lung Neoplasms ; diagnosis ; epidemiology ; etiology ; genetics ; Neoplasms, Multiple Primary ; diagnosis ; epidemiology ; etiology ; genetics ; Smoking ; adverse effects