Evaluation of Epidermal Growth Factor Receptor Gene Mutations in an Iranian Population with Non-Small Cell Lung Carcinoma
-
Hamzeh Salmani
,
Mahin Yahyaei
,
Reza Raoofian
,
Shiva Irani
,
Iman Salahshouri Far
,
Seyed Mohammad Akrami
Abstract
Background: Mutations of the epidermal growth factor receptor (EGFR) gene, predominantly in exons 18-21, have been highlighted to function as the crucial predictors of the response rate of patients with non-small cell lung cancer (NSCLC) to EGFR tyrosine kinase inhibitors (TKIs).
Methods: This study was performed at Tehran University of Medical Sciences. Data and information were retrospectively collected from the period between Dec 2010 and Apr 2014. Exons 18 to 21 of the EGFR were analyzed for any potential mutation by PCR, accompanied by DNA sequencing on 160 with pathological confirmation of NSCLC.
Results: Demographically, the male to female ratio was approximately 2:1, and a substantial difference in age between sexes was not observed (P=0.065), but a noticeable difference was found in the smoking variable, where 77.8% of males were smokers compared to 17.3% of women (odds ratio (OR) (95% CI) = 16.72 (7.15-39.11)). We found a frequency of 10.63% (17/160) for mutations found in exons 19 and 21, nonetheless, no mutations in exon 18 and exon 20 were observed. The most frequently observed mutations were c.2235_2249, del and c.2240_2257, del in exon 19 and p. L858R in exon 21. The c.2253A>G was found as a novel mutation that was the rarest mutation detected in this work. Interestingly, a remarkable negative association was revealed between smoking and mutation rates in NSCLC patients (OR (95% CI) = 0.13 (0.04- 0.46).
Conclusion: The occurrence of EGFR mutations is largely varied among the different states of Iran, probably due to variations in ethnicity, smoking rate, and sex ratio of participants.
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24. San Tam IY, Chung LP, Suen WS, et al (2006). Distinct epidermal growth factor receptor and KRAS mutation patterns in non–small cell lung cancer patients with different tobacco exposure and clinicopathologic features. Clin Cancer Res, 12(5):1647-53.
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26. Lee SJ, Lee J, Park YS, et al (2014). Impact of smoking on mortality of patients with non‐small cell lung cancer. Thoracic cancer, 5(1):43-9.
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28. Saffari, M., Modarressi, M.H., Shirkoohi, R, et al (2019). Plasma 5-miRNA as Biomarkers for Identifying Prostate Cancer Patients. Iran J Public Health, 48(9):1743-1745.
29. Schmid K, Oehl N, Wrba F, et al (2009). EGFR/KRAS/BRAF mutations in primary lung adenocarcinomas and corresponding locoregional lymph node metastases. Clin Cancer Res, 15(14):4554-60.
30. Sriram KB, Tan ME, Savarimuthu SM, et al(2011). Screening for activating EGFR mutations in surgically resected nonsmall cell lung cancer. Eur Respir J, 38(4):903-10.
31. Mäki-Nevala S, Rönty M, Morel M, et al (2014). Epidermal growth factor receptor mutations in 510 Finnish non–small-cell lung cancer patients. J Thorac Oncol, 9(6):886-91.
32. Helland Å, Skaug HM, Kleinberg L, et al (2011). EGFR gene alterations in a Norwegian cohort of lung cancer patients selected for surgery. J Thorac Oncol, 6(5):947-50.
33. Isaksson S, Bendahl P-O, Salomonsson A, et al (2013). Detecting EGFR alterations in clinical specimens—pitfalls and necessities. Virchows Arch, 463(6):755-64.
34. Chatziandreou I, Tsioli P, Sakellariou S, et al (2015). Comprehensive molecular analysis of NSCLC; clinicopathological associations. PLoS One, 10(7):e0133859.
35. Boch C, Kollmeier J, Roth A, et al (2013). The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort study. BMJ open, 3(4):e002560.
36. Reinmuth N, Jauch A, Xu EC, et al (2008). Correlation of EGFR mutations with chromosomal alterations and expression of EGFR, ErbB3 and VEGF in tumor samples of lung adenocarcinoma patients. Lung Cancer, 62(2):193-201.
37. Schittenhelm MM, Kollmannsberger C, Oechsle K, et al (2009). Molecular determinants of response to matuzumab in combination with paclitaxel for patients with advanced non-small cell lung cancer. Mol Cancer Ther, 8(3):481-9.
38. Zimmer S, Kahl P, Buhl TM, et al (2009). Epidermal growth factor receptor mutations in non-small cell lung cancer influence downstream Akt, MAPK and Stat3 signaling. J Cancer Res Clin Oncol, 135(5):723-30.
2. Weir HK, Thompson TD, Soman A, et al (2015). The past, present, and future of cancer incidence in the United States: 1975 through 2020. Cancer, 121(11):1827-37.
3. Bade BC, Cruz CSD (2020). Lung cancer 2020: epidemiology, etiology, and prevention. Clin Chest Med, 41(1):1-24.
4. Howlader N, Forjaz G, Mooradian MJ, et al (2020). The effect of advances in lung-cancer treatment on population mortality. N Engl J Med, 383(7):640-649.
5. Chiang AC, Herbst RS (2020). Frontline immunotherapy for NSCLC—the tale of the tail. Nat Rev Clin Oncol, 17(2):73-74.
6. Majem M, Juan O, Insa A, et al (2019). SEOM clinical guidelines for the treatment of non-small cell lung cancer (2018). Clin Transl Oncol, 21(1):3-17.
7. Hensing T, Chawla A, Batra R, et al (2014). A personalized treatment for lung cancer: molecular pathways, targeted therapies, and genomic characterization. Adv Exp Med Biol. 799:85-117.
8. Sequist LV, Lynch T J (2008). EGFR tyrosine kinase inhibitors in lung cancer: an evolving story. Annu Rev Med, 59:429-42.
9. Kobayashi K, Hagiwara K (2013). Epidermal growth factor receptor (EGFR) mutation and personalized therapy in advanced nonsmall cell lung cancer (NSCLC). Target Oncol, 8(1):27-33.
10. Zerbino DR, Achuthan P, Akanni W, et al (2017). Ensembl 2018. Nucleic Acids Res, 46(D1):D754-D761.
11. Untergasser A, Cutcutache I, Koressaar T, et al (2012). Primer3—new capabilities and interfaces. 40(15):e115.
12. Ye J, Coulouris G, Zaretskaya I, et al (2012). Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics, 13:134.
13. Rajai N, Ghanbari A, Yoosefi M, et al (2020). National and subnational trends in incidence and mortality of lung cancer in Iran from 1990 to 2016. Asia Pac J Clin Oncol, 16(3):129-136.
14. Rebuzzi SE, Alfieri R, La Monica S, et al (2020). Combination of EGFR-TKIs and chemotherapy in advanced EGFR mutated NSCLC: Review of the literature and future perspectives. Crit Rev Oncol Hematol, 146:102820.
15. Melosky B (2014). Review of EGFR TKIs in metastatic NSCLC, including ongoing trials. Front Oncol, 4:244.
16. Midha A, Dearden S, McCormack R (2015). EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res, 5(9):2892-911.
17. Basi A, Khaledi F, Niya MHK, et al (2018). Epidermal growth factor receptor mutations in lung adenocarcinomas: A single center study from Iran. Asian Pac J Cancer Prev, 19(1):111-114.
18. Mohammadzadeh S, Jowkar Z, Mirzai M, et al (2019). Epidermal Growth Factor Receptor (EGFR) Gene Mutation Analysis in Adenocarcinoma of Lung, the First Report from Iran. Iran J Pathol, 14(1):1-7.
19. Lynch TJ, Bell DW, Sordella R, et al (2004). Activating mutations in the epidermal growth factor receptor underlying responsiveness of non–small-cell lung cancer to gefitinib. N Engl J Med, 350(21):2129-39.
20. Sun P-L, Seol H, Lee HJ, et al (2012). High incidence of EGFR mutations in Korean men smokers with no intratumoral heterogeneity of lung adenocarcinomas: correlation with histologic subtypes, EGFR/TTF-1 expressions, and clinical features. J Thorac Oncol, 7(2):323-30.
21. Unal OU, Oztop I, Calibasi G, et al (2013). Relationship between epidermal growth factor receptor gene mutations and clinicopathological features in patients with non-small cell lung cancer in western Turkey. Asian Pac J Cancer Prev, 14(6):3705-9.
22. Gahr S, Stoehr R, Geissinger E, et al (2013). EGFR mutational status in a large series of Caucasian European NSCLC patients: data from daily practice. Br J Cancer, 109(7):1821-8.
23. Zhang Y-L, Yuan J-Q, Wang K-F, et al (2016). The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget, 7(48):78985-78993.
24. San Tam IY, Chung LP, Suen WS, et al (2006). Distinct epidermal growth factor receptor and KRAS mutation patterns in non–small cell lung cancer patients with different tobacco exposure and clinicopathologic features. Clin Cancer Res, 12(5):1647-53.
25. Takamochi K, Oh S, Suzuki K (2013). Differences in EGFR and KRAS mutation spectra in lung adenocarcinoma of never and heavy smokers. Oncol Lett, 6(5): 1207–1212.
26. Lee SJ, Lee J, Park YS, et al (2014). Impact of smoking on mortality of patients with non‐small cell lung cancer. Thoracic cancer, 5(1):43-9.
27. Nia PS, Weyler J, Colpaert C, et al (2005). Prognostic value of smoking status in operated non-small cell lung cancer. Lung Cancer, 47(3):351-9.
28. Saffari, M., Modarressi, M.H., Shirkoohi, R, et al (2019). Plasma 5-miRNA as Biomarkers for Identifying Prostate Cancer Patients. Iran J Public Health, 48(9):1743-1745.
29. Schmid K, Oehl N, Wrba F, et al (2009). EGFR/KRAS/BRAF mutations in primary lung adenocarcinomas and corresponding locoregional lymph node metastases. Clin Cancer Res, 15(14):4554-60.
30. Sriram KB, Tan ME, Savarimuthu SM, et al(2011). Screening for activating EGFR mutations in surgically resected nonsmall cell lung cancer. Eur Respir J, 38(4):903-10.
31. Mäki-Nevala S, Rönty M, Morel M, et al (2014). Epidermal growth factor receptor mutations in 510 Finnish non–small-cell lung cancer patients. J Thorac Oncol, 9(6):886-91.
32. Helland Å, Skaug HM, Kleinberg L, et al (2011). EGFR gene alterations in a Norwegian cohort of lung cancer patients selected for surgery. J Thorac Oncol, 6(5):947-50.
33. Isaksson S, Bendahl P-O, Salomonsson A, et al (2013). Detecting EGFR alterations in clinical specimens—pitfalls and necessities. Virchows Arch, 463(6):755-64.
34. Chatziandreou I, Tsioli P, Sakellariou S, et al (2015). Comprehensive molecular analysis of NSCLC; clinicopathological associations. PLoS One, 10(7):e0133859.
35. Boch C, Kollmeier J, Roth A, et al (2013). The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort study. BMJ open, 3(4):e002560.
36. Reinmuth N, Jauch A, Xu EC, et al (2008). Correlation of EGFR mutations with chromosomal alterations and expression of EGFR, ErbB3 and VEGF in tumor samples of lung adenocarcinoma patients. Lung Cancer, 62(2):193-201.
37. Schittenhelm MM, Kollmannsberger C, Oechsle K, et al (2009). Molecular determinants of response to matuzumab in combination with paclitaxel for patients with advanced non-small cell lung cancer. Mol Cancer Ther, 8(3):481-9.
38. Zimmer S, Kahl P, Buhl TM, et al (2009). Epidermal growth factor receptor mutations in non-small cell lung cancer influence downstream Akt, MAPK and Stat3 signaling. J Cancer Res Clin Oncol, 135(5):723-30.
| Files | ||
| Issue | Vol 51 No 2 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v51i2.8698 | |
| Keywords | ||
| Non-small cell lung cancer (NSCLC) Epidermal growth factor receptor (EGFR) Gene Mutation Clinicopathological data Iran | ||
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How to Cite
1.
Salmani H, Yahyaei M, Raoofian R, Irani S, Salahshouri Far I, Akrami SM. Evaluation of Epidermal Growth Factor Receptor Gene Mutations in an Iranian Population with Non-Small Cell Lung Carcinoma. Iran J Public Health. 2022;51(2):450-459.
