Türkiye’de akciğer kanserinde genetik mutasyonların bölgesel dağılımı (REDIGMA)

Giriş: Akciğer kanserinde standart kemoterapinin sonuçları çok tatmin edici değildir, bu nedenle hedefe yönelik tedavileri sağlayan genetik mutasyonları belirlemek önemlidir. Son raporlar, ırksal farklılığın ve bölgesel değişikliğin akciğer kanserinde mutasyon sıklığı üzerindeki etkilerini göstermiştir. Çalışmamızda küçük hücreli dışı akciğer kanseri (KHDAK)'nde genetik mutasyonların Türkiye'deki sıklığını ve bölgesel dağılımını belirlemeyi amaçladık. Materyal ve Metod: Türkiye'de akciğer kanserinde genetik mutasyonların bölgesel dağılımı (REDIGMA) çalışması, akciğer kanseri hastalarının takip edildiği ve hastaların biyopsisinde genetik mutasyon analizi yapılabilecek çok sayıda merkezde prospektif, kesitsel ve gözlemsel bir çalışma olarak gerçekleştirildi. Bulgular: Çalışmaya 25 farklı merkezden KHDAK tanısı konan 703 hasta (%77.7 erkek, ortalama yaş 63.3 ± 12.5 yıl) alındı. Hastalardan alınan tümör örnekleri %87.1 adenokarsinom, %6.4 skuamöz hücreli karsinom ve %6.5 diğer olarak bildirildi. Mutasyon testleri bu hastaların %18.9'unda pozitif bulundu. Mutasyonlar %69.9 EGFR, %26.3 ALK, %1.6 ROS ve %2.2 PDL idi. Mutasyonlar kadınlarda ve sigara içmeyenlerde istatistiksel olarak daha yüksek tespit edildi (p< 0.000, p< 0.001). Yine, adenokarsinomdaki mutasyonların sıklığı metastatik hastalıkta daha yüksekti. Hastanın yaşı, ikamet alanı, komorbiditesi, klinik evresi ve mutasyon sıklığı arasında farklılık saptanmamıştır. Sonuç: Çalışmamızın sonucunda Türkiye geneli mutasyon pozitifliği literatür ile karşılaştırıldığında Türkiye’de KHDAK'lı hastalarda EGFR mutasyon oranının Doğu Avrupa, Afrikalı-Amerikalı ve Kafkasyalı hastalara benzer ve Doğu Asya'dan daha düşük olduğu ortaya koyulmuştur

Regional distribution of genetic mutation in lung cancer in Turkey (REDIGMA)

Introduction: The results of standard chemotherapy in lung cancer are not very satisfactory, so it is important to identify geneticmutations that provide targeted therapies. Recent reports have suggested influences of racial difference on the frequency of mutationin lung cancer. We aimed to determine the frequency and regional distribution of genetic mutations of non-small cell lung cancer(NSCLC) in Turkey.Materials and Methods: Regional distribution of genetic mutations in lung cancer in Turkey (REDIGMA) study was carried out as aprospective, cross-sectional, observational study in a large number of centers in which lung cancer patients were followed and couldperform genetic mutation analysis on patients’ biopsy materials.Results: The 703 patients (77.7% male, mean age 63.3 ± 12.5 years) who were diagnosed as NSCLC from 25 different centers wereincluded in the study. Tumor samples from patients were reported as 87.1% adenocarcinoma, 6.4% squamous cell carcinoma and6.5% other. Mutation tests were found to be positive in 18.9% of these patients. The mutations were 69.9% EGFR, 26.3% ALK, 1.6%ROS and 2.2% PDL. Mutations were higher in women and non-smokers (p< 0.000, p< 0.001). Again, the frequency of mutations inadenocarcinoma was higher in metastatic disease. There was no difference between the patient’s age, area of residence, comorbidityand clinical stage and mutation frequency.Conclusion: Our study revealed that the EGFR mutation rate in Turkey with NSCLC was similar to East European, African–Americanand Caucasian patients, and was lower than in East Asia.

PDF

___

1. Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, et al. The global burden of cancer 2013. JAMA Oncology 2015;1:505-27.
2. T.C. Sağlık Bakanlığı Türkiye Halk Sağlığı Kurumu, Türkiye Kanser İstatistikleri. Date of access: 11.02.2019. Available from: https://hsgmsaglikgovtr/tr/kanser-istatistikleri/ yillar/495-2014-y%C4%B1l%C4%B1-t%C3%BCrkiyekanser-istatistiklerihtml. 2017.
3. World Health Organization, International Agency for Research on Cancer, Global Cancer Observatory. Lung, Source: Globocan 2018; Date of access: 15.03.2019. Available from: http://gcoiarcfr/today/data/factsheets/ cancers/15-Lung-fact-sheetpdf. 2019.
4. Yılmaz U. Küçük hücreli dışı akciğer kanserli hastalarda hedefe yönelik tedavi. Güncel Göğüs Hastalıkları Serisi 2013;1:124-9.
5. National Comprehensive Cancer Network (NCCN) Clinical Practise Guidelines in Oncology, Non-Small Cell Lung Cancer NCCN Evidence Blocks 2019. Date of access: 23.06.2019. Available from: https://www.nccn.org/professionals/physician_gls/pdf/nscl_blocks.pdf.
6. Akciğer Kanseri Yol Haritası, İmmüno-Onkoloji Derneği, Türk Akciğer Kanseri Derneği, Türk Tıbbi Onkoloji Derneği ve Türk Toraks Derneği. Date of access: 23.04.2018. Available from: http://takdorgtr/ AkcigerYolHaritasiTRbasimVERSIYONUpdf. 2016.
7. Shi Y, Au JSK, Thongprasert S, Srinivasan S, Tsai CM, Khoa MT, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non–smallcell lung cancer of adenocarcinoma histology (PIONEER). Journal of Thoracic Oncology 2014;9:154-62.
8. Sriuranpong V, Chantranuwat C, Huapai N, Chalermchai T, Leungtaweeboon K, Lertsanguansinchai P, et al. High frequency of mutation of epidermal growth factor receptor in lung adenocarcinoma in Thailand. Cancer Letters 2006;239:292-7.
9. Bozkurtlar E, Kaya H (eds). Molecular Pathology of Lung Cancer/Akciger Kanserinde Molekuler Patoloji. Nuclear Medicine Seminars. İstanbul: Galenos Yayinevi, 2018.
10. Pauwels P. Mutations in lung cancer with clinical significance. Toraks Cerrahisi Bülteni 2012;3:173-6.
11. Ou SHI. Republished: Lung cancer in never-smokers. Does smoking history matter in the era of molecular diagnostics and targeted therapy? Postgraduate Medical Journal. 2014;90:228-35.
12. Barta JA, Powell CA, Wisnivesky JP. Global epidemiology of lung cancer. Annals of Global Health 2019;85.
13. Nguyen-Ngoc T, Reck M, Tan DS, Peters S. Immunotherapy and targeted therapies in the treatment of non-small cell lung cancer. Journal-Immunotherapy and Targeted Therapies in the Treatment of Non-small Cell Lung Cancer 2017;13:Epub.
14. Ergün D, Savaş İ, Ergün R, Kaya A, Gülhan M. Akciğer kanseri ve ailesel kanser hikâyesi. Tuberk Toraks 2009;57:251-8.
15. Toyooka S, Matsuo K, Shigematsu H, Kosaka T, Tokumo M, Yatabe Y, et al. The impact of sex and smoking status on the mutational spectrum of epidermal growth factor receptor gene in non-small cell lung cancer. Clin Cancer Res 2007;13:5763-8.
16. Huang YT, Lin X, Liu Y, Chirieac LR, McGovern R, Wain J, et al. Cigarette smoking increases copy number alterations in non-small cell lung cancer. Proceedings of the National Academy of Sciences 2011;108:16345-50.
17. Ren JH, He WS, Yan GL, Jin M, Yang KY, Wu G. EGFR mutations in non‐small‐cell lung cancer among smokers and non‐smokers: A meta‐analysis. Environmental and Molecular Mutagenesis 2012;53:78-82.
18. Rahman S, Kondo N, Yoneda K, Takuwa T, Hashimoto M, Orui H, et al. Frequency of epidermal growth factor receptor mutations in Bangladeshi patients with adenocarcinoma of the lung. Int J Clin Oncol 2014;19:45-9.
19. Huang SF, Liu HP, Li LH, Ku YC, Fu YN, Tsai HY, et al. High frequency of epidermal growth factor receptor mutations with complex patterns in non–small cell lung cancers related to gefitinib responsiveness in Taiwan. Clinical Cancer Research 2004;10:8195-203.
20. Midha A, Dearden S, McCormack R. 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 2015;5:2892.
21. Yang PC, Shi Y, Au JSK, Srinivasan S, Cornelio GH, Tsai CM, et al. Molecular epidemiological prospective study of EGFR mutations from Asian patients (pts) with advanced lung adenocarcinoma (PIONEER). American Society of Clinical Oncology 2012.
22. Heralde F, Barzaga M, Tan-Liu N, Bernal S. P3. 02-056 EGFR mutation profile of NSCLC patients tested at the lung center of the philippines. J Thorac Oncol 2017;12:S2257-S8.
23. Papadopoulou E, Tsoulos N, Tsirigoti A, Apessos A, Agiannitopoulos K, Metaxa-Mariatou V, et al. Determination of EGFR and KRAS mutational status in Greek non-small-cell lung cancer patients. Oncology Letters 2015;10:2176-84.
24. Arrieta O, Cardona AF, Bramuglia GF, Gallo A, CamposParra AD, Serrano S, et al. Genotyping non-small cell lung cancer (NSCLC) in Latin America. J Thorac Oncol2011;6:1955-9.
25. Cote ML, Haddad R, Edwards DJ, Atikukke G, Gadgeel S, Soubani AO, et al. Frequency and type of epidermal growth factor receptor mutations in African Americans with nonsmall cell lung cancer. J Thorac Oncol 2011;6:627-30.
26. Leary AF, de Castro DG, Nicholson AG, Ashley S, Wotherspoon A, O’Brien ME, et al. Establishing an EGFR mutation screening service for non-small cell lung cancer– Sample quality criteria and candidate histological predictors. Eur J Cancer 2012;48:61-7.
27. Saffroy R, Morère JF, Bosselut N, Innominato PF, Hamelin J, Trédaniel J, et al. Impact of country of birth on genetic testing of metastatic lung adenocarcinomas in France: African women exhibit a mutational spectrum more similar to Asians than to Caucasians. Oncotarget 2017;8:50792.
28. Unal OU, Oztop I, Calibasi G, Baskin Y, Koca D, Demir N, et al. 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 2013;14:3705-9.
29. Tezel GG, Şener E, Aydın Ç, Önder S. Prevalence of epidermal growth factor receptor mutations in patients with nonsmall cell lung cancer in Turkish population. Balkan Medical Journal 2017;34:567.