1.The Impact of Cigarette Smoking on the Frequency of and Qualitative Differences in KRAS Mutations in Korean Patients with Lung Adenocarcinoma.
Hye Ryun KIM ; 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
Yonsei Medical Journal 2013;54(4):865-874
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
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Adult
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Aged
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Aged, 80 and over
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Asian Continental Ancestry Group/genetics
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Female
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Humans
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Incidence
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Lung Neoplasms/drug therapy/etiology/*genetics/pathology
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Male
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Middle Aged
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*Mutation
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Mutation Rate
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Proportional Hazards Models
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Proto-Oncogene Proteins/*genetics
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Receptor, Epidermal Growth Factor/antagonists & inhibitors/genetics
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Smoking/adverse effects/*genetics
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Treatment Outcome
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ras Proteins/*genetics