Araştırma Makalesi
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BRCA1/2 normal meme kanserli kadınlarda genotip-fenotip ilişkisinin araştırılması: Türkiye'den tek merkez deneyimi

Yıl 2021, Cilt: 12 Sayı: 3, 349 - 356, 29.09.2021
https://doi.org/10.18663/tjcl.948240

Öz

Amaç: Meme kanserlerinin yaklaşık %10'unun kalıtsal olduğu ve bunların yaklaşık %20'sinden BRCA1/2 genlerinin sorumlu olduğu bilinmektedir. Yapılan araştırmalar, meme kanserinde BRCA1/2 dışındaki birçok genin mutasyonlarının da yatkınlığa neden olduğunu göstermiştir. Bu çalışmada meme kanserli Türk kadınlarda diğer kanser yatkınlık genlerinin araştırılması amaçlanmıştır.
Gereç ve Yöntemler: Bu retrospektif çalışmaya Ankara Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi Genetik Bölümü'nde 2016-2021 yılları arasında değerlendirilen 66 kadın hasta dahil edildi. Hastaların kansere yatkınlık genleri, yeni nesil dizileme tekniği (NGS) kullanılarak incelendi.
Bulgular: Hastaların ortalama tanı yaşı 43 ± 8.0 idi. Genetik analiz ile 66 hastanın 9'unda (%13,63) nedensel gen tespit edildi. Bu genler ATM (%13), CHEK2 (%36), FANCC (%13), MUTYH (%13) ve PALB2'dir (%25). Nedensel varyantı olan hastalar ve diğerleri gruplandırılarak tanı yaşı, tümör lokalizasyonu, tümörün histopatolojik tipi, östrojen/progesteron reseptör durumu, cerbb2, evre, tanı anındaki metastaz ve kanserli akraba sayısı gibi parametreler açısından karşılaştırıldı. Gruplar arasında istatistiksel bir ilişki bulunamadı.
Sonuç: Bu çalışmada meme kanserli Türk kadınlarında BRCA1/2 dışındaki kansere yatkınlık genlerinin nedensel varyantlarının saptanma oranı %13,63 olarak belirlendi. Kanserli bireylerde NGS ile çoklu gen testlerinin yapılması, taşıyıcı bireylerin doğru tanı ve uygun tedavi almalarını ve gerekli taramalara yönlendirilmelerini sağlayacaktır.

Kaynakça

  • 1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90.
  • 2. Broca P. Traité des tumeurs. Vols. 1 and 2. Paris: Asselin; 1866–9
  • 3. Honrado E, Benítez J, Palacios J. The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications. Mod Pathol 2005; 18: 1305–20
  • 4. Stratton MR, Rahman N. The emerging landscape of breast cancer susceptibility. Nat Genet 2008; 40: 17-22.
  • 5. Vargas AC, Reis-Filho JS, Lakhani SR. Phenotype-genotype correlation in familial breast cancer. J Mammary Gland Biol Neoplasia 2011; 16: 27–40.
  • 6. Beck AC, Yuan H, Liao J et al. Rate of BRCA mutation in patients tested under NCCN genetic testing criteria. Am J Surg 2020; 219: 145-9.
  • 7. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991; 19: 403-10.
  • 8. Richards S, Aziz N, Bale S et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17: 405-24.
  • 9. Thompson D, Easton D. The genetic epidemiology of breast cancer genes. J Mammary Gland Biol Neoplasia 2004; 9: 221–36.
  • 10. Peto J, Mack TM. High constant incidence in twins and other relatives of women with breast cancer. Nat Genet 2000; 26: 411-4.
  • 11. Gerdes AM, Cruger DG, Thomassen M, Kruse TA. Evaluation of two different models to predict BRCA1 and BRCA2 mutations in a cohort of Danish hereditary breast and/or ovarian cancer families. Clin Genet 2006; 69: 171-8.
  • 12. Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer 2011; 12: 68-78.
  • 13. Easton DF, Pooley KA, Dunning AM et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 2007; 447: 1087-93.
  • 14. Cox A, Dunning AM, Garcia-Closas M et al. A common coding variant in CASP8 is associated with breast cancer risk. Nat Genet 2007; 39: 352-8.
  • 15. Nevanlinna H, Bartek J. The CHEK2 gene and inherited breast cancer susceptibility. Oncogene 2006; 25: 5912-9.
  • 16. Rainville I, Hatcher S, Rosenthal E et al. High risk of breast cancer in women with biallelic pathogenic variants in CHEK2. Breast Cancer Res Treat. 2020; 180: 503-9.
  • 17. NCCN clinical practice guidelines in oncology, genetic/familial high-risk assessment: breast and ovarian (version 3. 2019). https://www.nccn.org/professionals/physician_gls/pdf/ genetics_bop.pdf. (5 Haziran 2021).
  • 18. Antoniou AC, Casadei S, Heikkinen T et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med 2014; 371: 497-506.
  • 19. Zhou J, Wang H, Fu F et al. Spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer: Screening of 16,501 unselected patients with breast cancer and 5890 controls by next-generation sequencing. Cancer 2020; 126: 3202-8.
  • 20. Antoniou AC, Casadei S, Heikkinen T et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med 2014; 371: 497-506.
  • 21. Janatová M, Borecká M, Soukupová J et al. PALB2 jako další kandidátní gen pro genetické testování u pa-cientů s hereditárním karcinomem prsu v České republice [PALB2 as Another Candidate Gene for Genetic Testing in Patients with Hereditary Breast Cancer in Czech Republic]. Klin Onkol 2016; 29: 31-4.
  • 22. Weber-Lassalle N, Hauke J, Ramser J et al. BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer. Breast Cancer Res 2018; 20: 7.
  • 23. Mazouzi A, Battistini F, Moser SC et al. Repair of UV-Induced DNA Damage Independent of Nucleotide Excision Repair Is Masked by MUTYH. Mol Cell 2017; 68: 797-807.
  • 24. Rennert G, Lejbkowicz F, Cohen I, Pinchev M, Rennert HS, Barnett-Griness O. MutYH mutation carriers have increased breast cancer risk. Cancer 2012; 118: 1989-93.
  • 25. Jerzak KJ, Mancuso T, Eisen A. Ataxia-telangiectasia gene (ATM) mutation heterozygosity in breast cancer: a narrative review. Curr Oncol 2018; 25: 176-80

Investigation of genotype-phenotype relationship in women with BRCA1/2 normal breast cancer: A single-center experience from Turkey

Yıl 2021, Cilt: 12 Sayı: 3, 349 - 356, 29.09.2021
https://doi.org/10.18663/tjcl.948240

Öz

Aim: It is known that approximately 10% of breast cancers are hereditary, and BRCA1/2 genes are responsible for
approximately 20% of these. Studies have shown that mutations of many genes other than BRCA1/2 in breast cancer also
cause this predisposition. In this study, it was aimed to investigate other causative cancer susceptibility genes in women
with breast cancer.
Material and Methods: In this retrospective study, 66 female patients who were evaluated in Ankara Dışkapı Yıldırım
Beyazıt Training and Research Hospital Genetics Department between 2016-2020 were included. Cancer susceptibility
genes of the patients were examined using next-generation sequencing technique (NGS).
Results: Mean age at diagnosis of the patients was 43 ± 8.0. By genetic analysis, causative genes were identified in 9
(13.63%) of 66 patients. These genes are ATM (%11), BRIP1 (%11), CHEK2 (%34), FANCC (%11), MUTYH (%11) and PALB2
(%22). Patients with a causal variant and others were grouped, and compared in terms of parameters such as age at
diagnosis, tumor localization, histopathological type of tumor, estrogen/progesterone receptor status, c-erbB2, stage,
metastasis at diagnosis, and number of relatives with cancer. No statistical relationship was found between the groups.
Conclusion: This study determined the rate of detection of causal variants of cancer susceptibility genes other than
BRCA1/2 in women with breast cancer who applied to the medical genetics department as 13.63%. Performing multiple
gene tests with the NGS in cancer individuals will allow carrier individuals to receive correct diagnosis and appropriate
treatment and to be directed to necessary screenings.

Kaynakça

  • 1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90.
  • 2. Broca P. Traité des tumeurs. Vols. 1 and 2. Paris: Asselin; 1866–9
  • 3. Honrado E, Benítez J, Palacios J. The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications. Mod Pathol 2005; 18: 1305–20
  • 4. Stratton MR, Rahman N. The emerging landscape of breast cancer susceptibility. Nat Genet 2008; 40: 17-22.
  • 5. Vargas AC, Reis-Filho JS, Lakhani SR. Phenotype-genotype correlation in familial breast cancer. J Mammary Gland Biol Neoplasia 2011; 16: 27–40.
  • 6. Beck AC, Yuan H, Liao J et al. Rate of BRCA mutation in patients tested under NCCN genetic testing criteria. Am J Surg 2020; 219: 145-9.
  • 7. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991; 19: 403-10.
  • 8. Richards S, Aziz N, Bale S et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17: 405-24.
  • 9. Thompson D, Easton D. The genetic epidemiology of breast cancer genes. J Mammary Gland Biol Neoplasia 2004; 9: 221–36.
  • 10. Peto J, Mack TM. High constant incidence in twins and other relatives of women with breast cancer. Nat Genet 2000; 26: 411-4.
  • 11. Gerdes AM, Cruger DG, Thomassen M, Kruse TA. Evaluation of two different models to predict BRCA1 and BRCA2 mutations in a cohort of Danish hereditary breast and/or ovarian cancer families. Clin Genet 2006; 69: 171-8.
  • 12. Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer 2011; 12: 68-78.
  • 13. Easton DF, Pooley KA, Dunning AM et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 2007; 447: 1087-93.
  • 14. Cox A, Dunning AM, Garcia-Closas M et al. A common coding variant in CASP8 is associated with breast cancer risk. Nat Genet 2007; 39: 352-8.
  • 15. Nevanlinna H, Bartek J. The CHEK2 gene and inherited breast cancer susceptibility. Oncogene 2006; 25: 5912-9.
  • 16. Rainville I, Hatcher S, Rosenthal E et al. High risk of breast cancer in women with biallelic pathogenic variants in CHEK2. Breast Cancer Res Treat. 2020; 180: 503-9.
  • 17. NCCN clinical practice guidelines in oncology, genetic/familial high-risk assessment: breast and ovarian (version 3. 2019). https://www.nccn.org/professionals/physician_gls/pdf/ genetics_bop.pdf. (5 Haziran 2021).
  • 18. Antoniou AC, Casadei S, Heikkinen T et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med 2014; 371: 497-506.
  • 19. Zhou J, Wang H, Fu F et al. Spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer: Screening of 16,501 unselected patients with breast cancer and 5890 controls by next-generation sequencing. Cancer 2020; 126: 3202-8.
  • 20. Antoniou AC, Casadei S, Heikkinen T et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med 2014; 371: 497-506.
  • 21. Janatová M, Borecká M, Soukupová J et al. PALB2 jako další kandidátní gen pro genetické testování u pa-cientů s hereditárním karcinomem prsu v České republice [PALB2 as Another Candidate Gene for Genetic Testing in Patients with Hereditary Breast Cancer in Czech Republic]. Klin Onkol 2016; 29: 31-4.
  • 22. Weber-Lassalle N, Hauke J, Ramser J et al. BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer. Breast Cancer Res 2018; 20: 7.
  • 23. Mazouzi A, Battistini F, Moser SC et al. Repair of UV-Induced DNA Damage Independent of Nucleotide Excision Repair Is Masked by MUTYH. Mol Cell 2017; 68: 797-807.
  • 24. Rennert G, Lejbkowicz F, Cohen I, Pinchev M, Rennert HS, Barnett-Griness O. MutYH mutation carriers have increased breast cancer risk. Cancer 2012; 118: 1989-93.
  • 25. Jerzak KJ, Mancuso T, Eisen A. Ataxia-telangiectasia gene (ATM) mutation heterozygosity in breast cancer: a narrative review. Curr Oncol 2018; 25: 176-80
Toplam 25 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm Özgün Makale
Yazarlar

Neslihan Duzkale 0000-0001-6122-5316

Aysun Gökce 0000-0002-4026-6503

Tülay Eren 0000-0002-0088-1149

Gökşen İnanç İmamoğlu 0000-0003-0356-0727

Mustafa Altınbaş

Yayımlanma Tarihi 29 Eylül 2021
Yayımlandığı Sayı Yıl 2021 Cilt: 12 Sayı: 3

Kaynak Göster

APA Duzkale, N., Gökce, A., Eren, T., İmamoğlu, G. İ., vd. (2021). BRCA1/2 normal meme kanserli kadınlarda genotip-fenotip ilişkisinin araştırılması: Türkiye’den tek merkez deneyimi. Turkish Journal of Clinics and Laboratory, 12(3), 349-356. https://doi.org/10.18663/tjcl.948240
AMA Duzkale N, Gökce A, Eren T, İmamoğlu Gİ, Altınbaş M. BRCA1/2 normal meme kanserli kadınlarda genotip-fenotip ilişkisinin araştırılması: Türkiye’den tek merkez deneyimi. TJCL. Eylül 2021;12(3):349-356. doi:10.18663/tjcl.948240
Chicago Duzkale, Neslihan, Aysun Gökce, Tülay Eren, Gökşen İnanç İmamoğlu, ve Mustafa Altınbaş. “BRCA1/2 Normal Meme Kanserli kadınlarda Genotip-Fenotip ilişkisinin araştırılması: Türkiye’den Tek Merkez Deneyimi”. Turkish Journal of Clinics and Laboratory 12, sy. 3 (Eylül 2021): 349-56. https://doi.org/10.18663/tjcl.948240.
EndNote Duzkale N, Gökce A, Eren T, İmamoğlu Gİ, Altınbaş M (01 Eylül 2021) BRCA1/2 normal meme kanserli kadınlarda genotip-fenotip ilişkisinin araştırılması: Türkiye’den tek merkez deneyimi. Turkish Journal of Clinics and Laboratory 12 3 349–356.
IEEE N. Duzkale, A. Gökce, T. Eren, G. İ. İmamoğlu, ve M. Altınbaş, “BRCA1/2 normal meme kanserli kadınlarda genotip-fenotip ilişkisinin araştırılması: Türkiye’den tek merkez deneyimi”, TJCL, c. 12, sy. 3, ss. 349–356, 2021, doi: 10.18663/tjcl.948240.
ISNAD Duzkale, Neslihan vd. “BRCA1/2 Normal Meme Kanserli kadınlarda Genotip-Fenotip ilişkisinin araştırılması: Türkiye’den Tek Merkez Deneyimi”. Turkish Journal of Clinics and Laboratory 12/3 (Eylül 2021), 349-356. https://doi.org/10.18663/tjcl.948240.
JAMA Duzkale N, Gökce A, Eren T, İmamoğlu Gİ, Altınbaş M. BRCA1/2 normal meme kanserli kadınlarda genotip-fenotip ilişkisinin araştırılması: Türkiye’den tek merkez deneyimi. TJCL. 2021;12:349–356.
MLA Duzkale, Neslihan vd. “BRCA1/2 Normal Meme Kanserli kadınlarda Genotip-Fenotip ilişkisinin araştırılması: Türkiye’den Tek Merkez Deneyimi”. Turkish Journal of Clinics and Laboratory, c. 12, sy. 3, 2021, ss. 349-56, doi:10.18663/tjcl.948240.
Vancouver Duzkale N, Gökce A, Eren T, İmamoğlu Gİ, Altınbaş M. BRCA1/2 normal meme kanserli kadınlarda genotip-fenotip ilişkisinin araştırılması: Türkiye’den tek merkez deneyimi. TJCL. 2021;12(3):349-56.


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