TRİPLE-NEGATİF MEME KANSERİ HASTALARINDA RANK, RANKL VE OPG GENLERİNDEKİ POLİMORFİZMLERİN BELİRLENMESİ VE KEMİK METASTAZI ÜZERİNE ETKİSİNİN İNCELENMESİ

Yıl 2019, Cilt: 9 Sayı: 4, 316 - 320, 31.12.2019

Şükran Yıldız Hani Al Saadonı Mehmet Alıustaoglu Arzu Ergen , Sadrettin Pence

https://doi.org/10.33808/clinexphealthsci.533548

Öz

Anahtar Kelimeler

Meme, Metastaz

Determination of Rank, Rankl and Opg Gene Polymorphisms in Triple-Negative Breast Cancer Patients and Invesgation of its Effect on Bone Metastasis

Öz

Objective: Triple negative breast cancer (TNBC) is a sub-type of breast cancer with the worst prognosis and highest risk of mortality. Bone metastasis is the most common metastasis type among women with breast cancer. RANK and OPG, are the members of the family of tumor necrosis factor (TNF), which is effective on osteoblastic and osteoclastic mechanisms. RANKL, interacts with RANK and leads to bone resorption, whereas it inhibits bone destruction when it interacts with OPG.
Methods: In this study, we investigated the polymorphisms of RANK, RANKL and OPG genes and their effects on bone metastasis in 45 patients with triple negative breast cancer and 30 healthy controls, using PCR, RFLP and agarose gel electrophoresis techniques.
Results: The RANKL genotype and allele distribution analysis revealed a significantly increased CC genotype incidence in patients with TNBC and bone metastasis (p=0.011) and in those without bone metastasis (p=0.004) compared to the control group. The OPG genotype and allele distribution analysis revealed significantly increased C allele incidence in patients with TNBC and bone metastasis (p=0.004) compared to the control group. Likewise, the CC genotype (p=0.001) and C allele incidences (p=0.001) were observed to be significantly increased in patients with TNBC compared to healthy controls.
Conclusion: This study is one of the first studies investigating all three RANK/RANKL/OPG gene polymorphisms and the relationship between breast cancer and bone metastasis in our country. We believe that our study will shed light onto further studies to be conducted on triple negative breast cancer and bone metastasis.

Anahtar Kelimeler

Breast, Metastasis, Triple Negative

Kaynakça

• 1. T.C. Sağlık Bakanlığı 2013, 2014 Türkiye Kanser İstatistikleri. Ankara: Halk Sağlığı Genel Müdürlüğü (İnternette) 2014, Erişim 17.11.2017, http://kanser.gov.tr/daire-faaliyetleri/kanser-istatistikleri/2106-2013-yılı-türkiye-kanser-istatistikleri.html
• 2. Mavaddat N, Antoniou AC, Easton DF, Garcia-Closas M. Genetic susceptibility to breast cancer. Mol Oncol 2010; 4(3):174-91.
• 3. Nurten R, Buyukbabani N, Bermek E, Ilhan R, Iplikci A. Hormon reseptörlerinin meme karsinomlarının histopatolojik tiplerine göre değerlendirilmesi. Türk Patoloji Dergisi 1998; 4-1;46-51.
• 4. Tekin V, Yıldırım M, Erkan N, Postacı H, Çetin DA, Selek E, et al. Meme kanserli subgruplarının sıklığı ve sağkalım üzerine etkileri. İzmir Eğitim ve Araştırma Hastanesi Tıp Dergisi 2013;17:88-97.
• 5. Kuo WH, Chang YY, Lai LC, Tsai MH, Hsiao CK, Chang KJ, et al. Molecular characteristics and metastasis predictor genes of triple-negative breast cancer: a clinical study of triple-negative breast carcinomas. PloS one 2012; 7(9):e45831.
• 6. Hudis CA, Gianni L. Triple-negative breast cancer: an unmet medical need. The Oncologist 2011;16(1):1-11.
• 7. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 2011;121(7):2750–2767.
• 8. Swain S. Triple-negative breast cancer: Metastatic risk and role of platinum agents. Presented at the Annual Meeting of the American Society for Clinical Oncology; Clinical Science Symposium; Chicago; 2008
• 9. Pala EE, Bayol Ü, Cumurcu S, Keskin E. Triple-Negatif/Bazal Benzeri Meme Kanserinin İmmünohistokimyasal Özellikleri. Türk Patoloji Derg 2012; 28: 238-244.
• 10. Wahba HA, El-Hadaad HA. Current approaches in treatment of triple-negative breast cancer. Cancer biology & medicine 2015; 12(2):106.
• 11. Muss HB. Breast cancer and differential diagnosis of benign nodules, in Cecil Textbook of Medicine, JCB L Goldman, Editor. W.B. Saunders: Philadelphia. 2000.p.1373-1380
• 12. Lorenzo JA, Canalis E, Raisz LG. Metabolic bone dissease. Williams Textbook Of Endocrinology, 11th Edn. Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, editors. Saunders Elsevier: Philadelphia. 2007.p.1296-1310.
• 13. Ando K, Mori K, Rédini F, Heymann D. RANKL/RANK/OPG: key therapeutic target in bone oncology. Current drug discovery Technologies 2008;5(3):263-268.
• 14. Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Archives of biochemistry and biophysics 2008; 473(2):139-146.
• 15. Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, et al. Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 1998; 273(23):14363–7.
• 16. American Society for Bone and Mineral Research President's Committee on Nomenclature. Proposed standard nomenclature for new tumor necrosis factor family members involved in the regulation of bone resorption. The American Society for Bone and Mineral Research President's Committee on Nomenclature. J Bone Miner Res 2000;15(12):2293-6.
• 17. Suvannasankha A, Chirgwin JM. Role of bone-anabolic agents in the treatment of breast cancer bone metastases. Breast Cancer Research 2014; 16(6): 484.
• 18. Mansour EG, Rravdin PM, Dressler L. Prognostic factors in early breast cancer. Cancer 1994;74:381-400.
• 19. Aksoy S, Dizdar O, Harputluoglu H, Altundag K. Demographic, clinical, and pathological characteristics of Turkish triple-negative breast cancer patients: single center experience. Ann Oncol 2007; 18(11): 1904-1906.
• 20. Ünçel M, Aköz G, Yıldırım Z, Pişkin G, Değirmenci M, Solakoğlu Kahraman D, et al. Meme kanserinin klinikopatolojik özelliklerinin moleküler alt tipe göre değerlendirilmesi. Tepecik Eğit ve Araşt Hast Dergisi 2015;25(3):151-156
• 21. Li R, Zhang K, Penedo TL, Kragel CP, Grizzle WE, Hameed O, et al. The RANK Pathway in Advanced Breast Cancer: Does Src Play a Role? Appl Immunohistochem Mol Morphol 2016;24(1):42-50.
• 22. Weichhaus M, Segaran P, Renaud A, Geerts D, Connelly L. Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis. Cancer Med 2014;3(5):1112-25.
• 23. Hein A, Bayer CM, Schrauder MG, Häberle L, Heusinger K, Strick R, et al. Polymorphisms in the RANK/RANKL genes and their effect on bone specific prognosis in breast cancer patients. Biomed Res Int. 2014;2014:842452.
• 24. Santini D, Schiavon G, Vincenzi B, Gaeta L, Pantano F, Russo A, et al. Receptor activator of NF-kB (RANK) expression in primary tumors associates with bone metastasis occurrence in breast cancer patients. PLoS One 2011;6(4):e19234.
• 25. Yin J, Wang L, Tang W, Wang X, Lv L, Shao A, et al. RANK rs1805034 T>C polymorphism is associated with susceptibility of Esophageal Cancer in a Chinese Population. PLoS One 2014;9(7):e101705.
• 26. Thomson CA, McCullough ML, Wertheim BC, Chlebowski RT, Martinez ME, Stefanick ML, et al. Nutrition and Physical Activity Cancer Prevention Guidelines, Cancer Risk, and Mortality in the Women's Health Initiative. Cancer Prev Res 2014;7(1): 42–53
• 27. Reyes ME, Fujii T, Branstetter D, Krishnamurthy S, Masuda H, Wang X, et al. Poor prognosis of patients with triple-negative breast cancer can be stratified by RANK and RANKL dual expression. Breast Cancer Res Treat 2017;164(1):57-67.
• 28. Wang J, Lu K, Song Y, Zhao S, Ma W, Xuan Q, et al. RANKL and OPG polymorphisms are associated with aromatase inhibitor-related musculoskeletal adverse events in Chinese Han Breast Cancer Patients. PLoS One 2015;10 (7):e0133964
• 29. Omar HS, Shaker OG, Nassar YH, Marzouk SA, El Marzouky MS. The association between RANKL and osteoprotegerin gene polymorphisms with breast cancer. Molecular and cellular biochemistry 2015; 403(1-2):219-229.
• 30. Ney JT, Juhasz-Boess I, Gruenhage F, Graeber S, Bohle RM, Pfreundschuh M, et al. Genetic polymorphism of the OPG gene associated with breast cancer. BMC Cancer 2013;13(1): 40.