BRCA Mutasyonu Otoskleroz İçin Risk Faktörü Olabilir mi?

Amaç: Bu çalışmanın amacı BRCA mutasyonu olan hastalarda otoskleroz varlığını araştırmaktır.Gereç ve Yöntemler: BRCA mutasyonu olan ve meme kanseri nedeniyle opere edilen hastalar ile sağlıklı kontrol grubu arasında işitsel fonksiyonlar karşılaştırıldı. Çalışmaya 20 sağlıklı kontrol ve 20 BRCA 1 veya BRCA 2 mutasyonuna sahip toplamda 40 birey dahil edildi. Her iki grup, yaş aralığı 2538 arasında ve yaş ortalaması 31.7±3.5 yıl olan kadın katılımcılardan oluşturuldu. BRCA mutasyonuna sahip hastaların yaş ortalaması 34±2.7 iken sağlıklı kontrollerin yaş ortalaması 29.4±2.5ʼdi. Tüm katılımcılara baş-boyun muayenesi, saf ses odyometrisi, akustik refleks ve timpanometritestleri yapıldı. Akut ve kronik orta kulak iltihabı, baş ve boyun travması, işitme bozukluğuna yol açabilecek ilaç kullanımı ve kulak operasyon öyküsü olan hastalar çalışma dışı bırakıldı. Bulgular: Her iki gruptan da tip A timpanometri, normal akustik refleks ve normal işitme seviyeleri ≤ 20dB elde edildi. Sağlıklı kontroller ile BRCA mutasyonu olan hastalar arasında 250 Hz - 2000 Hz arasındaki kemik ve hava yolu düzeylerinde istatistiksel olarak anlamlı bir fark gözlenmedi.Sonuç: BRCA mutasyonuna sahip hastalar ile sağlıklı kontroller arasında saf ses odyometri sonuçları açısından istatiksel anlamlı farklılık saptanmadı. BRCA mutasyonu olan hastalarda otosklerotik odak varlığını göstermek için ileri ve histopatolojik çalışmalar gerekebilir

Anahtar Kelimeler:

BRCA, Otoskleroz, Osteoprotegerin

Can BRCA Mutation be a Risk Factor for Otosclerosis?

Objective: The aim of this study was to investigate the presence of otosclerosis in patients with BRCA mutation.Material and Methods: Auditory functions were compared between patients with BRCA mutation who were operated due to breast cancer and healthy controls. The study included a total of 40 individuals, among those, 20 were healthy controls, and 20 had BRCA 1 and BRCA 2 mutation. All participants were female in both groups. Age range was 25-38 years, and mean age was 31.7±3.5 years. Mean age among patients with BRCA mutation and healthy controls were 34±2.7 and 29.4±2.5, respectively. All participants were undertaken head-neck examination, pure-tone audiometry, acoustic reflex and tympanometry tests. Patients with acute and chronic otitis media, head and neck trauma, drug use that may lead to hearing impairment, and ear operation history were excluded from the study.Results: All participants of both groups revealed type A tympanometry, normal acoustic reflex, and a normal auditory level ≤ 20dB . No statistically significant difference was observed in the bone and airway levels between 250 Hz - 2000 Hz between healthy controls and patients with BRCA mutation. Conclusion: No significant difference was observed in the pure-tone audiometry between patients with BRCA mutation and healthy controls. Further and histopathologic studies may be needed to demonstrate the presence of otosclerotic focus in patients with BRCA mutation

Keywords:

BRCA, Otosclerosis, Osteoprotegerin,

PDF

___

1. Chole RA, McKenna M. Pathophysiology of otosclerosis. Otol Neurotol 2001; 22:249-57.
2. Stankovic K, McKenna M. Current research in otosclerosis. Otol Neurotol 2006; 22:249-57.
3. Niedermeyer HP, Gantumur T, Neubert WJ, Arnold W. Measles virus and otosclerosis. Adv Otorhinolaryngol 2007; 65:86-92.
4. Weber M. The blue mantles in otosclerosis: A contribution to the pathology of the labyrinth capsule. Ann Otol Rhinol Laryngol 1933; 42:438-54.
5. Hofbauer LC, Neubauer A, Heufelder AE. Receptor activator of nuclear factor-kappaB ligand and osteoprotegerin: Potential implications for the pathogenesis and treatment of malignant bone diseases. Cancer 2001; 92:460-70.
6. Udagawa N, Takahashi N, Yasuda H, Mizuno A, Itoh K, Ueno Y, Shinki T, Gillespie MT, Martin TJ, Higashio K, Suda T. Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development. Endocrinology 2000; 141:3478-84.
7. Zehnder AF, Kristiansen AG, Adams JC, Kujawa SG, Merchant SN, McKenna MJ. Osteoprotegerin knockout mice demonstrate abnormal remodeling of the otic capsule and progressive hearing loss. Laryngoscope 2006; 116(2):201-6.
8. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tulinius H, Thorlacius S, Eerola H, Nevanlinna H, Syrjäkoski K, Kallioniemi OP, Thompson D, Evans C, Peto J, Lalloo F, Evans DG, Easton DF. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: A combined analysis of 22 studies. Am J Hum Genet 2003; 72(5):1117-30.
9. Priyadarshi S, Ray CS, Biswal NC, Nayak SR, Panda KC, Desai A, Ramchander PV. Genetic association and altered gene expression of osteoprotegerin in otosclerosis patients. Ann Hum Genet 2015; 79(4):225-37.
10. Widschwendter M, Burnell M, Fraser L, Rosenthal AN, Philpott S, Reisel D, Dubeau L, Cline M, Pan Y, Yi PC, Gareth Evans D, Jacobs IJ, Menon U, Wood CE, Dougall WC. Osteoprotegerin (OPG), the endogenous inhibitör of receptor activator of NF-κB ligand (RANKL), is dysregulated in BRCA mutation carriers. EBioMedicine 2015; 2(10):1331-9.
11. Iyer PV, Gristwood RE. Histopathology of the stapes in otosclerosis. Pathology 1984; 16:30-8.
12. Declau F, Van Spaendonck M, Timmermans JP, Michaels L, Liang J, Qiu JP, Van de Heyning P. Prevalence of otosclerosis in an unselected series of temporal bones. Otol Neurotol 2001; 22:596-602.
13. Karosi T, Konya J, Petkó M, Szabó LZ, Pytel J, Joeri J, Sziklai I. Two subgroups of stapes fixation: Otosclerosis and pseudootosclerosis. Laryngoscope 2005;115:1968-73.
14. Karosi T, Sziklai I. Etiopathogenesis of otosclerosis. Eur Arch Otorhinolaryngol 2010; 267:1337-49.
15. Kostenuik PJ, Shalhoub V. Osteoprotegerin: A physiological and pharmacological inhibitor of bone resorption. Curr Pharm Des 2001; 7(8):613-35.
16. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Lüthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, RenshawGegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ. Osteoprotegerin: A novel secreted protein involved in the regulation of bone density. Cell 1997; 89(2):309-19.
17. Zehnder AF, Kristiansen AG, Adams JC, Merchant SN, McKenna MJ. Osteoprotegerin in the inner ear may inhibit bone remodeling in the otic capsule. Laryngoscope 2005; 115(1):172-7.
18. Potocka-Bakłażec M, Sakowicz-Burkiewicz M, Kuczkowski J, Pawełczyk T, Stankiewicz C, Sierszeń W, Jankowski Z, Buczny J. Expression of TNF-α, OPG, IL-1β And the presence of the measles virus RNA in the stapes ofnthe patients with otosclerosis. Eur Arch Otorhinolaryngol 2015; 272(8):1907-12.
19. Karosi T, Jókay I, Kónya J, Szabó LZ, Pytel J, Jóri J, Szalmás A, Sziklai I. Detection of osteoprotegerin and TNF-alpha mRNA in ankylotic Stapes footplates in connection with measles virus positivity. Laryngoscope 2006; 116(8):1427-33.
20. Karosi T, Csomor P, Szalmás A, Kónya J, Petkó M, Sziklai I. Osteoprotegerin expression and sensitivity in otosclerosis with different histological activity. Eur Arch Otorhinolaryngol 2011; 268(3):357-65.
21. Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 2007; 25(11):1329-33.
22. Odén L, Akbari M, Zaman T, Singer CF, Sun P, Narod SA, Salmena L, Kotsopoulos J. Plasma osteoprotegerin and breast cancer risk in BRCA1 and BRCA2 mutation carriers. Oncotarget 2016; 7(52):86687-94.