title: Association of epidermal growth factor receptor and K-Ras mutations with smoking history in non-small cell lung cancer patients.
abstract: Lung cancer, a major health problem affecting the epithelial lining of the lower respiratory tract, is considered to be one of the deadliest types of cancer in males and females and it is well-known that smoking is the chief cause of lung cancer. In addition to smoking and environmental factors, genetic susceptibility may also contribute to the development of lung cancer. Previous studies have shown that certain non-small cell lung cancer (NSCLC) patients harbor gain-of-function mutations in the epidermal growth factor receptor gene (EGFR). Phosphorylated EGFR triggers the activation of intracellular signal transduction pathways, including the RAS-MAPK, PI3K-Akt and STAT pathways. However, K-Ras gene point mutations in codons 12, 13 or 61 cause the inactivation of GTPase activity which results in overstimulation of cellular growth and gives rise to neoplastic development. Our aim was to investigate the presence and association of EGFR and K-Ras mutations in 50 primary NSCLC patients with a smoking history by using real-time PCR and sequencing. EGFR mutations were detected in four patients (8%). Two of these mutations were L858R mutations and the remaining two were deletion mutations spanning between codons 746 and 750. The L858R mutation was significantly associated with smoking status (P=0.003). K-Ras codon 12 and 61 mutations were also observed in four patients. However, no association was observed between K-Ras mutations and the tumor staging, gender, histology and smoking status of the patients.
authors: Departments of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University, Kocamustafapasa, Istanbul 34098;
authors: Onur
authors: O
authors: Baykara
authors: Merve
authors: M
authors: Tansarikaya
authors: Ahmet
authors: A
authors: Demirkaya
authors: Kamil
authors: K
authors: Kaynak
authors: Serhan
authors: S
authors: Tanju
authors: Alper
authors: A
authors: Toker
authors: Nur
authors: N
authors: Buyru
keywords: K-Ras; epidermal growth factor receptor; non-small cell lung cancer; smoking
references: J Natl Cancer Inst. 2000 Jun 7;92(11):918-23
references: 10841827
references: Pathol Oncol Res. 2001;7(1):6-13
references: 11349214
references: Cancer Res. 2005 Jun 15;65(12):5076-83
references: 15958551
references: Cancer Res. 1993 May 15;53(10 Suppl):2379-85
references: 7683573
references: Science. 2004 Jun 4;304(5676):1497-500
references: 15118125
references: Lung Cancer. 2009 Jun;64(3):295-300
references: 19058870
references: Clin Cancer Res. 2005 Feb 1;11(3):1167-73
references: 15709185
references: J Cancer Res Clin Oncol. 2010 Dec;136(12):1937-44
references: 20237940
references: Clin Cancer Res. 2007 May 15;13(10):2890-6
references: 17504988
references: Clin Cancer Res. 2006 Apr 15;12(8):2538-44
references: 16638863
references: J Cell Physiol. 2007 Mar;210(3):740-9
references: 17133351
references: Pathobiology. 2008;75(1):2-8
references: 18334834
references: Oncogene. 2002 Oct 21;21(48):7435-51
references: 12379884
references: N Engl J Med. 2008 Mar 13;358(11):1160-74
references: 18337605
references: Cancer. 1993 Sep 1;72(5):1573-80
references: 8394199
references: Clin Cancer Res. 2006 Mar 1;12(5):1647-53
references: 16533793
references: Oncol Rep. 2006 Dec;16(6):1245-52
references: 17089045
references: Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13306-11
references: 15329413
references: Br J Cancer. 2006 Mar 27;94(6):896-903
references: 16552419
references: PLoS Med. 2005 Jan;2(1):e17
references: 15696205
references: J Clin Oncol. 2005 Apr 10;23(11):2513-20
references: 15738541
references: Eur J Cancer. 2008 May;44(7):946-53
references: 18396036
references: Cancer Res. 2007 Mar 15;67(6):2643-8
references: 17363584
references: Chest. 1997 Oct;112(4 Suppl):216S-228S
references: 9337293
references: Clin Cancer Res. 2009 Jul 15;15(14):4554-60
references: 19584155
references: Ann Oncol. 2007 Jan;18(1):99-103
references: 17060486
references: Lancet Oncol. 2008 Oct;9(10):962-72
references: 18804418
references: J Clin Oncol. 2006 Apr 10;24(11):1700-4
references: 16505411
references: Lung Cancer. 2008 Sep;61(3):328-39
references: 18304690
references: Cancer Res. 2004 Dec 15;64(24):8919-23
references: 15604253
references: Cancer Epidemiol Biomarkers Prev. 2000 Nov;9(11):1193-7
references: 11097226
references: J Surg Oncol. 1992 Nov;51(3):147-52
references: 1434639
references: J Cancer Res Clin Oncol. 2008 May;134(5):569-77
references: 17932690
references: N Engl J Med. 2004 May 20;350(21):2129-39
references: 15118073
references: Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6049-55
references: 17062680
references: J Natl Cancer Inst. 2005 Mar 2;97(5):339-46
references: 15741570
references: Lung Cancer. 2000 Nov;30(2):135-44
references: 11086207
references: Cancer Res. 1989 Sep 1;49(17):4682-9
references: 2547513
references: Int J Cancer. 2001 Oct 15;94(2):153-6
references: 11668491
references: Recent Results Cancer Res. 1999;151:3-12
references: 10337715
references: FEBS Lett. 2010 Jun 18;584(12):2699-706
references: 20388509