The Impact of Cigarette Smoking on the Frequency of and Qualitative Differences in KRAS Mutations in Korean Patients with Lung Adenocarcinoma
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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.
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.
참고문헌 (37)
- Jemal A, "Cancer statistics, 2009", CA Cancer J Clin, 59, pp.225~249 (2009)
- 정민규, "Prognostic and Predictive Value of Carcinoembryonic Antigen and Cytokeratin-19 Fragments Levels in Advanced Non-Small Cell Lung Cancer Patients Treated with Gefitinib or Erlotinib", Yonsei Medical Journal, 53(5), pp.931~939 (2012), 연세대학교의과대학[DOI]
- Mao C, "KRAS mutations and resistance to EGFR-TKIs treatment in patients with non-small cell lung cancer: a meta-analysis of 22 studies", Lung Cancer, 69, pp.272~278 (2010)
- Thatcher N, "Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer)", Lancet, 366, pp.1527~1537 (2005)
- Paez JG, "EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy", Science, 304, pp.1497~1500 (2004)
- Lynch TJ, "Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib", N Engl J Med, 350, pp.2129~2139 (2004)
- Gandhi J, "Alterations in genes of the EGFR signaling pathway and their relationship to EGFR tyrosine kinase inhibitor sensitivity in lung cancer cell lines", PLoS One, 4, pp.e4576~ (2009)
- Jackman DM, "Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials", Clin Cancer Res, 15, pp.5267~5273 (2009)
- Pao W, "EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib", Proc Natl Acad Sci U S A, 101, pp.13306~13311 (2004)
- Douillard JY, "Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial", J Clin Oncol, 28, pp.744~752 (2010)
- Jackman DM, "Phase II clinical trial of chemotherapy-naive patients > or = 70 years of age treated with erlotinib for advanced non-small-cell lung cancer", J Clin Oncol, 25, pp.760~766 (2007)
- Miller VA, "Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib", J Clin Oncol, 26, pp.1472~1478 (2008)
- Pao W, "KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib", PLoS Med, 2, pp.e17~ (2005)
- Linardou H, "Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer", Lancet Oncol, 9, pp.962~972 (2008)
- van Zandwijk N, "EGFR and KRAS mutations as criteria for treatment with tyrosine kinase inhibitors: retro- and prospective observations in non-small-cell lung cancer", Ann Oncol, 18, pp.99~103 (2007)
- Schneider CP, "Epidermal growth factor receptor-related tumor markers and clinical outcomes with erlotinib in non-small cell lung cancer: an analysis of patients from german centers in the TRUST study", J Thorac Oncol, 3, pp.1446~1453 (2008)
- Han SW, "Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib", J Clin Oncol, 23, pp.2493~2501 (2005)
- Riely GJ, "KRAS mutations in non-small cell lung cancer", Proc Am Thorac Soc, 6, pp.201~205 (2009)
- Roberts PJ, "Personalized medicine in non-small-cell lung cancer: is KRAS a useful marker in selecting patients for epidermal growth factor receptor-targeted therapy?", J Clin Oncol, 28, pp.4769~4777 (2010)
- De Luca A, "Predictive biomarkers to tyrosine kinase inhibitors for the epidermal growth factor receptor in non-small-cell lung cancer", Curr Drug Targets, 11, pp.851~864 (2010)
- Suda K, "Biological and clinical significance of KRAS mutations in lung cancer: an oncogenic driver that contrasts with EGFR mutation", Cancer Metastasis Rev, 29, pp.49~60 (2010)
- Ahrendt SA, "Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung", Cancer, 92, pp.1525~1530 (2001)
- Kakegawa S, "Clinicopathological features of lung adenocarcinoma with KRAS mutations", Cancer, 117, pp.4257~4266 (2011)
- Massarelli E, "KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer", Clin Cancer Res, 13, pp.2890~2896 (2007)
- Han SW, "Optimization of patient selection for gefitinib in non-small cell lung cancer by combined analysis of epidermal growth factor receptor mutation, K-ras mutation, and Akt phosphorylation", Clin Cancer Res, 12, pp.2538~2544 (2006)
- Kim ES, "Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial", Lancet, 372, pp.1809~1818 (2008)
- Beasley MB, "The 2004 World Health Organization classification of lung tumors", Semin Roentgenol, 40, pp.90~97 (2005)
- Riely GJ, "Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma", Clin Cancer Res, 14, pp.5731~5734 (2008)
- Therasse P, "New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada", J Natl Cancer Inst, 92, pp.205~216 (2000)
- Li M, "The status of KRAS mutations in patients with non-small cell lung cancers from mainland China", Oncol Rep, 22, pp.1013~1020 (2009)
- Keohavong P, "Detection of K-ras mutations in lung carcinomas: relationship to prognosis", Clin Cancer Res, 2, pp.411~418 (1996)
- Rosell R, "Molecular staging of non-small cell lung cancer according to K-ras genotypes", Clin Cancer Res, 2, pp.1083~1086 (1996)
- Sakuma Y, "Distinctive evaluation of nonmucinous and mucinous subtypes of bronchioloalveolar carcinomas in EGFR and K-ras gene-mutation analyses for Japanese lung adenocarcinomas: confirmation of the correlations with histologic subtypes and gene mutations", Am J Clin Pathol, 128, pp.100~108 (2007)
- Bae NC, "EGFR, ERBB2, and KRAS mutations in Korean non-small cell lung cancer patients", Cancer Genet Cytogenet, 173, pp.107~113 (2007)
- Wu CC, "Reversed mutation rates of KRAS and EGFR genes in adenocarcinoma of the lung in Taiwan and their implications", Cancer, 113, pp.3199~3208 (2008)
- Lee YJ, "Lung cancer in never smokers: change of a mindset in the molecular era", Lung Cancer, 72, pp.9~15 (2011)
- Naumov GN, "Combined vascular endothelial growth factor receptor and epidermal growth factor receptor (EGFR) blockade inhibits tumor growth in xenograft models of EGFR inhibitor resistance", Clin Cancer Res, 15, pp.3484~3494 (2009)