The Effects of EGFR Exon 19 747–750 Deletion on the Risk of Developing Lung Cancer

Year 2019, Volume: 6 Issue: 7, 109 - 113, 30.07.2019

Duygu Yolal Ertural , Erdinç Nayır Rabia Bozdoğan Arpacı Ebru Derici Eker , Nazan Eras Didem Derici Yıldırım , Etem Akbaş

https://doi.org/10.17546/msd.569279

Abstract

Objective: Although smoking is the most significant factor in the etiology of lung cancer, other environmental pollutants and genetic predisposition also play major roles in its development. Histopathologically, lung cancers are divided into two major types, as small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). The latter accounts for almost 85% of all lung cancers with a very aggressive course and being associated with a high rate of mortality. Among the genetic mutations with prognostic value in NSCLC, the epidermal growth factor receptor (EGFR) mutation is most frequently found in 50 to 80% of cases. The EGFR is a transmembrane glycoprotein with tyrosine kinase activity which is associated with both normal cell growth and malignant transformations. Material and Methods: In the present study, we aimed to evaluate the effects of exon 19 747–750 deletion in the EGFR gene on the risk of developing lung cancer and to examine its potential relationship with the different histopathological types of lung cancer. The study sample comprised a total of 178 patients diagnosed with lung cancer at Mersin University, Medical Faculty, Oncology Clinics, and 192 age- and sex-matched healthy individuals as the control group. Deoxyribonucleic acid (DNA) isolation was performed using the standard salt-water precipitation method, while the mutation screening and genotyping analyses were carried out with a polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses. Results: The frequency of mutant EGFR exon-19 deletion in the control group was 15.1%, increasing to 36.9% in the lung cancer group, and increasing the risk of developing lung cancer by 2.64 times (p: 0.014). This increase did not significantly differ between the histopathological types of lung cancer (p: 0.76). Conclusion: Considering the distribution of lung cancer patients in different age groups, it is obvious that advanced age is a risk factor for the development of EGFR mutation and lung cancers (p<0.001).

Keywords

Lung cancer, EGFR gene, Exon 19 deletion

Thanks

The authors wish to thank all of the patients and volunteers who participated in this study. This study has been approved by the Mersin University Clinical Research Ethics Committee (Number: 2013/428).

References

• 1. Wong MCS, Lao XQ, Ho KF. Incidence and mortality of lung cancer: global trends and association with socioeconomic status. Sci Rep 2017 Oct 30;7(1):14300.
• 2. http://www.who.int/cancer/en/July 16, 2016
• 3. Dela Cruz CS, Tanoue LT, Matthay RA. Lung Cancer: Epidemiology, Etiology, and Prevention. Clin Chest Med 2011 Dec;32(4):605-44.
• 4. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 2008 May; 83(5):584-94.
• 5. Shtivelman E, Hensing T, Simon GR, et al. Molecular pathways and therapeutic targets in lung cancer. Oncotarget 2014 Mar 30;5(6):1392-433.
• 6. da Cunha Santos G, Shepherd FA, Tsao MS. EGFR mutations and lung cancer. Ann Rev Pathol 2011 Feb 29;6:49–69.
• 7. Siegelin MD, Borczuk AC. Epidermal growth factor receptor mutations in lung adenocarcinoma. Lab Invest 2014 Feb;94(2):129–37.
• 8. Mitsudomi T, Yatabe Y. Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS Journal 2010 Jan;277(2):301–8.
• 9. Lee SM. Is EGFR expression important in non-small cell lung cancer? Thorax. 2006 Feb; 61(2):98-9.
• 10. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988 Feb 11;16(3):1215.
• 11. Dearden S, Stevens J, Wu YL, Blowers D. Mutation İncidence and Coincidence in Non Small-Cell Lung Cancer: Meta-Analyses by Ethnicity and Histology (mutMap). Ann Oncol 2013 Sep;24(9):2371–6.
• 12. Asano H, Toyooka S, Tokumo M, et al. Detection of EGFR Gene Mutation in Lung Cancer by Mutant-Enriched Polymerase Chain Reaction Assay. Clin Cancer Res 2006 Jan 1;12(1):43-48.
• 13. Shiau CJ, Babwah JP, da Cunha Santos G, et al. Sample features associated with success rates in population-based EGFR mutation testing. J Thorac Oncol 2014 Jul; 9(7):947-956.
• 14. D'Angelo SP, Pietanza MC, Johnson ML, et al. Incidence of EGFR Exon 19 Deletions and L858R in Tumor Specimens From Men and Cigarette Smokers With Lung Adenocarcinomas. J Clin Oncol 2011 May 20;29(15):2066-70.
• 15. Baek JH, Sun JM, Min YJ, et al. Efficacy of EGFR tyrosine kinase inhibitors in patients with EGFR-mutated nonsmall cell lung cancer except both exon 19 deletion and exon 21 L858R: A retrospective analysis in Korea. Lung Cancer 2015 Feb; 87(2): 148-154.
• 16. Bircan S, Baloglu H, Kucukodaci Z, Bircan A. EGFR and KRAS mutations in Turkish non-small cell lung cancer patients: a pilot study. Med Oncol 2014 Aug;31(8):87.
• 17. Li M, Zhang Q, Liu L, et al. The different clinical significance of EGFR mutations in exon 19 and 21 in non-small cell lung cancer patients of China. Neoplasma 2011; 58(1):74-81.
• 18. Quan X, Gao H, Wang Z, et al. Epidermal Growth Factor Receptor Somatic Mutation Analysis İn 354 Chinese Patients With Non-Small Cell Lung Cancer. Oncology Letters 2018 Feb;15(2):2131-8.
• 19. Kawada I, Soejima K, Watanabe H, et al. An alternative method for screening EGFR mutation using RFLP in non-small cell lung cancer patients. J Thorac Oncol 2008 Oct;3(10):1096-103.