Abstract 1126: The L858R mutation of the EGFR gene might be associated with smoking in non-small cell lung cancer

Abstract

Abstract Lung cancer, which involves malignant proliferation of the epithelial lining of the lower respiratory tract is the most common cause of cancer death in men and is second only to breast cancer in women. Smoking is considered to be one of the principal causes of lung cancer. However, as only a subgroup of smokers ever develop the disease, it has been suggested that genetic susceptibility may contribute to the risk. Recent studies have shown that some 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 such as RAS-MAPK, PI3K-Akt and STAT. On the other hand, point mutations in codons 12, 13 or 61 of the K-Ras gene inactivate the GTPase activity of the K-Ras resulting in continuous stimulation of autonomous growth and contribute to neoplastic development. The aim of this study was to investigate the presence and relationship of EGFR and K-Ras mutations with smoking history in a series of 50 primary NSCLC tumors. DNA was isolated by digestion of tissue samples using a DNA isolation kit. EGFR and K-ras mutations were investigated by Real Time-PCR assay. To confirm the mutations exons 18-21 of the EGFR gene and the whole K-ras gene were also analyzed by cycle sequencing in the samples found positive by the real-time PCR assay. In four patients (8%) EGFR mutations were detected. Two of these mutations were L858R and the remaining two were deletion mutations spanning codons from 746 to 750. The L858R mutation was significantly associated with smoking status (p=0.003). K-ras codon 12 and 61 mutations were also observed in 4 patients. However, no association was observed between K-ras mutations and tumor staging, sex, histology and smoking status of the patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1126. doi:10.1158/1538-7445.AM2011-1126