Investigation of BRCA1-BRCA2 Gene Variations in Breast Cancer Patients in the Eastern Anatolian Region of Turkey: A Study of Genetic Predisposition and Clinical Outcomes
Öz
Objective: This study aims to investigate BRCA1 and BRCA2 gene variations in breast cancer patients in Eastern Anatolia region and to evaluate the effects of these variations on patients' genetic predisposition and clinical outcome.
Materials and Methods: The study was conducted on 146 women diagnosed with breast cancer or with a family history of multiple breast cancer cases between 2020 and 2023. Genomic DNA was isolated from the participants and the entire BRCA1/2 genes were sequenced. The data were statistically analysed.
Results: The study identified 17 different genetic variations in the BRCA genes. Four of these variations were classified as pathogenic, potentially causing significant changes in protein structure and increasing the risk of cancer. In addition, some variations were classified as Variants of Uncertain Significance (VUS), whose health effects remain unclear.
Conclusion: This study elucidates the relationship between genetic predisposition and cancer development by investigating BRCA1 and BRCA2 gene variations in breast cancer patients in the Eastern Anatolian region. Four pathogenic variations in the BRCA genes were identified that have the potential to increase cancer risk. In addition, 12 variations were classified as VUS and their health effects have yet to be determined. Our findings provide important information for genetic counselling and disease management, enabling the development of personalised treatment approaches for patients.
Anahtar Kelimeler
BRCA1 BRCA2 Breast Cancer Genetic Variation Eastern Anatolia Region
Kaynakça
- 1. Yeşil H, Kıran B, Alkan H. Using complementary and alternative medicine in patients with breast cancer diagnosis at Afyon Kocatepe University. Kocatepe Medical Journal 2018; 19(2):42-7.
- 2. Kote-Jarai Z, Leongamornlert D, Saunders E, Tymrakiewicz M, Castro E, Mahmud N. BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients. British journal of cancer 2011; 105(8):1230-4.
- 3. Taylan S, Çelik GK. Ailesel meme kanseri öyküsü olan ve olmayan kadınlarda meme kanseri tanılama davranışları. Cukurova Medical Journal 2020; 45(4):1467-75.
- 4. Yavuz E, Eyupoglu C. An effective approach for breast cancer diagnosis based on routine blood analysis features. Medical & Biological Engineering & Computing 2020; 58(7):1583-601.
- 5. Aytekin MŞ, Çetin Ö, Kahraman A. Ebelik bölümü öğrencilerinin ve annelerinin kendi kendine meme muayenesi yapma durumları ve meme kanseri korkusu arasındaki ilişkinin belirlenmesi. Anatolian Journal of Health Research 2022; 2(3):93-100.
- 6. Kocak HS, Ece ZO, Gungormus Z. Birinci derece yakını meme kanserli kadınların korku düzeyinin erken tanı davranışlarına etkisi. Hemşirelik Bilimi Dergisi 2022; 5(1):22-9.
- 7. Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. Bmj 2014; 348.
- 8. Aksoy F, Tezcan Unlu H, Cecener G, Guney Eskiler G, Egeli U, Tunca B. Identification of CHEK2 Germline Mutations in BRCA1/2-and PALB2-Negative Breast and Ovarian Cancer Patients. Human heredity 2022; 87(2):21-33.
- 9. Kriege M, Hollestelle A, Jager A, Huijts P, Berns E, Sieuwerts A. Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy. British journal of cancer 2014; 111(5):1004-13.
- 10. Liu Y, Xu Y, Ouyang T, Li J, Wang T, Fan Z. Association between CHEK2 H371Y mutation and response to neoadjuvant chemotherapy in women with breast cancer. BMC cancer 2015; 15:1-8.
- 11. Li X, Xue H, Luo N, Han T, Li M, Jia D. The first case report of a patient with oligodendroglioma harboring CHEK2 germline mutation. Frontiers in Genetics 2022; 13:718689.
- 12. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. Journal of the National Cancer Institute 2009; 101(2):80-7.
- 13. Tai YC, Domchek S, Parmigiani G, Chen S. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. Journal of the National Cancer Institute 2007; 99(23):1811-4.
- 14. Antoniou AC, Spurdle AB, Sinilnikova OM, Healey S, Pooley KA, Schmutzler RK. Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. The American Journal of Human Genetics 2008; 82(4):937-48.
- 15. Shive HR, West RR, Embree LJ, Azuma M, Sood R, Liu P. brca2 in zebrafish ovarian development, spermatogenesis, and tumorigenesis. Proceedings of the National Academy of Sciences 2010; 107(45):19350-5.
- 16. Johansson PA, Nathan V, Bourke LM, Palmer JM, Zhang T, Symmons J. Evaluation of the contribution of germline variants in BRCA1 and BRCA2 to uveal and cutaneous melanoma. Melanoma research 2019; 29(5):483-90.
- 17. Krishnan R, Patel PS, Hakem R. BRCA1 and metastasis: outcome of defective DNA repair. Cancers 2021; 14(1):108.
- 18. Kwong A, Shin VY, Ho JC, Kang E, Nakamura S, Teo S-H. Comprehensive spectrum of BRCA1 and BRCA2 deleterious mutations in breast cancer in Asian countries. Journal of medical genetics 2016; 53(1):15-23.
- 19. Zhang Y, Wu H, Yu Z, Li L, Zhang J, Liang X. Germline variants profiling of BRCA1 and BRCA2 in Chinese Hakka breast and ovarian cancer patients. BMC cancer 2022; 22(1):842.
- 20. Chapla A, John A, Singh A, Yadav P, Joel A, Thumaty D. BRCA1 and BRCA2 gene mutation spectrum and high frequency of BRCA1 185delAG among breast and ovarian cancer patients from Southern India. 2023.
- 21. Kopanos C, Tsiolkas V, Kouris A, Chapple CE, Aguilera MA, Meyer R. VarSome: the human genomic variant search engine. Bioinformatics 2019; 35(11):1978.
- 22. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J. 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. Genetics in medicine 2015; 17(5):405-23.
- 23. Bhaskaran SP, Chandratre K, Gupta H, Zhang L, Wang X, Cui J. Germline variation in BRCA1/2 is highly ethnic‐specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients. International journal of cancer 2019; 145(4):962-73.
- 24. Kulkarni A, Carley H. Advances in the recognition and management of hereditary cancer. British Medical Bulletin 2016; 120(1).
- 25. Bahsi T, Erdem HB. Spectrum of BRCA1/BRCA2 variants in 1419 Turkish breast and ovarian cancer patients: a single center study. Turkish Journal of Biochemistry 2020; 45(1):83-90.
- 26. Eccles B, Copson E, Maishman T, Abraham J, Eccles D. Understanding of BRCA VUS genetic results by breast cancer specialists. BMC cancer 2015; 15:1-9.
- 27. Jimenez-Sainz J, Jensen RB. Imprecise medicine: BRCA2 variants of uncertain significance (VUS), the challenges and benefits to integrate a functional assay workflow with clinical decision rules. Genes 2021; 12(5):780.
- 28. Yost S, Ruark E, Alexandrov LB, Rahman N. Insights into BRCA cancer predisposition from integrated germline and somatic analyses in 7632 cancers. JNCI Cancer Spectrum 2019; 3(2):pkz028.
- 29. Culver JO, Brinkerhoff C, Clague J, Yang K, Singh K, Sand S. Variants of uncertain significance in BRCA testing: evaluation of surgical decisions, risk perception, and cancer distress. Clinical genetics 2013; 84(5):464-72.
- 30. Chern J-Y, Lee SS, Frey MK, Lee J, Blank SV. The influence of BRCA variants of unknown significance on cancer risk management decision-making. Journal of gynecologic oncology 2019; 30(4).
- 31. Adam F, Fluri M, Scherz A, Rabaglio M. Occurrence of variants of unknown clinical significance in genetic testing for hereditary breast and ovarian cancer syndrome and Lynch syndrome: a literature review and analytical observational retrospective cohort study. BMC medical genomics 2023; 16(1):7.
Türkiye'nin Doğu Anadolu Bölgesindeki Meme Kanseri Hastalarında BRCA1-BRCA2 Gen Varyasyonlarının Araştırılması: Genetik Yatkınlık ve Klinik Sonuçlar Üzerine Bir Çalışma
Öz
Amaç: Bu çalışmanın amacı Doğu Anadolu Bölgesi'ndeki meme kanserli hastalarda BRCA1 ve BRCA2 gen varyasyonlarını araştırmak ve bu varyasyonların hastaların genetik yatkınlığı ve klinik sonuçları üzerindeki etkilerini değerlendirmektir.
Gereç ve Yöntemler: Çalışma, 2020-2023 yılları arasında meme kanseri tanısı almış veya ailesinde birden fazla meme kanseri vakası öyküsü olan 146 kadın üzerinde yürütülmüştür. Katılımcılardan genomik DNA izole edilmiş ve BRCA1/2 genlerinin tamamı dizilenmiştir. Veriler istatistiksel olarak analiz edilmiştir.
Sonuçlar: Çalışmada BRCA genlerinde 17 farklı genetik varyasyon tespit edilmiştir. Bu varyasyonlardan dördü patojenik olarak sınıflandırılmış, potansiyel olarak protein yapısında önemli değişikliklere neden olmuş ve kanser riskini artırmıştır. Buna ek olarak, bazı varyasyonlar, sağlık üzerindeki etkileri belirsizliğini koruyan Belirsiz Öneme Sahip Varyantlar (VUS) olarak sınıflandırılmıştır.
Sonuç: Bu çalışma, Doğu Anadolu bölgesindeki meme kanseri hastalarında BRCA1 ve BRCA2 gen varyasyonlarını araştırarak genetik yatkınlık ve kanser gelişimi arasındaki ilişkiyi aydınlatmaktadır. BRCA genlerinde kanser riskini artırma potansiyeline sahip dört patojenik varyasyon tanımlanmıştır. Buna ek olarak, 12 varyasyon VUS olarak sınıflandırılmıştır ve bunların sağlık üzerindeki etkileri henüz belirlenmemiştir. Bulgularımız genetik danışmanlık ve hastalık yönetimi için önemli bilgiler sunmakta ve hastalar için kişiselleştirilmiş tedavi yaklaşımlarının geliştirilmesine olanak sağlamaktadır.
Anahtar Kelimeler
BRCA1 BRCA2 Meme Kanseri Genetik Varyasyon Doğu Anadolu Bölgesi
Kaynakça
- 1. Yeşil H, Kıran B, Alkan H. Using complementary and alternative medicine in patients with breast cancer diagnosis at Afyon Kocatepe University. Kocatepe Medical Journal 2018; 19(2):42-7.
- 2. Kote-Jarai Z, Leongamornlert D, Saunders E, Tymrakiewicz M, Castro E, Mahmud N. BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients. British journal of cancer 2011; 105(8):1230-4.
- 3. Taylan S, Çelik GK. Ailesel meme kanseri öyküsü olan ve olmayan kadınlarda meme kanseri tanılama davranışları. Cukurova Medical Journal 2020; 45(4):1467-75.
- 4. Yavuz E, Eyupoglu C. An effective approach for breast cancer diagnosis based on routine blood analysis features. Medical & Biological Engineering & Computing 2020; 58(7):1583-601.
- 5. Aytekin MŞ, Çetin Ö, Kahraman A. Ebelik bölümü öğrencilerinin ve annelerinin kendi kendine meme muayenesi yapma durumları ve meme kanseri korkusu arasındaki ilişkinin belirlenmesi. Anatolian Journal of Health Research 2022; 2(3):93-100.
- 6. Kocak HS, Ece ZO, Gungormus Z. Birinci derece yakını meme kanserli kadınların korku düzeyinin erken tanı davranışlarına etkisi. Hemşirelik Bilimi Dergisi 2022; 5(1):22-9.
- 7. Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. Bmj 2014; 348.
- 8. Aksoy F, Tezcan Unlu H, Cecener G, Guney Eskiler G, Egeli U, Tunca B. Identification of CHEK2 Germline Mutations in BRCA1/2-and PALB2-Negative Breast and Ovarian Cancer Patients. Human heredity 2022; 87(2):21-33.
- 9. Kriege M, Hollestelle A, Jager A, Huijts P, Berns E, Sieuwerts A. Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy. British journal of cancer 2014; 111(5):1004-13.
- 10. Liu Y, Xu Y, Ouyang T, Li J, Wang T, Fan Z. Association between CHEK2 H371Y mutation and response to neoadjuvant chemotherapy in women with breast cancer. BMC cancer 2015; 15:1-8.
- 11. Li X, Xue H, Luo N, Han T, Li M, Jia D. The first case report of a patient with oligodendroglioma harboring CHEK2 germline mutation. Frontiers in Genetics 2022; 13:718689.
- 12. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. Journal of the National Cancer Institute 2009; 101(2):80-7.
- 13. Tai YC, Domchek S, Parmigiani G, Chen S. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. Journal of the National Cancer Institute 2007; 99(23):1811-4.
- 14. Antoniou AC, Spurdle AB, Sinilnikova OM, Healey S, Pooley KA, Schmutzler RK. Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. The American Journal of Human Genetics 2008; 82(4):937-48.
- 15. Shive HR, West RR, Embree LJ, Azuma M, Sood R, Liu P. brca2 in zebrafish ovarian development, spermatogenesis, and tumorigenesis. Proceedings of the National Academy of Sciences 2010; 107(45):19350-5.
- 16. Johansson PA, Nathan V, Bourke LM, Palmer JM, Zhang T, Symmons J. Evaluation of the contribution of germline variants in BRCA1 and BRCA2 to uveal and cutaneous melanoma. Melanoma research 2019; 29(5):483-90.
- 17. Krishnan R, Patel PS, Hakem R. BRCA1 and metastasis: outcome of defective DNA repair. Cancers 2021; 14(1):108.
- 18. Kwong A, Shin VY, Ho JC, Kang E, Nakamura S, Teo S-H. Comprehensive spectrum of BRCA1 and BRCA2 deleterious mutations in breast cancer in Asian countries. Journal of medical genetics 2016; 53(1):15-23.
- 19. Zhang Y, Wu H, Yu Z, Li L, Zhang J, Liang X. Germline variants profiling of BRCA1 and BRCA2 in Chinese Hakka breast and ovarian cancer patients. BMC cancer 2022; 22(1):842.
- 20. Chapla A, John A, Singh A, Yadav P, Joel A, Thumaty D. BRCA1 and BRCA2 gene mutation spectrum and high frequency of BRCA1 185delAG among breast and ovarian cancer patients from Southern India. 2023.
- 21. Kopanos C, Tsiolkas V, Kouris A, Chapple CE, Aguilera MA, Meyer R. VarSome: the human genomic variant search engine. Bioinformatics 2019; 35(11):1978.
- 22. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J. 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. Genetics in medicine 2015; 17(5):405-23.
- 23. Bhaskaran SP, Chandratre K, Gupta H, Zhang L, Wang X, Cui J. Germline variation in BRCA1/2 is highly ethnic‐specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients. International journal of cancer 2019; 145(4):962-73.
- 24. Kulkarni A, Carley H. Advances in the recognition and management of hereditary cancer. British Medical Bulletin 2016; 120(1).
- 25. Bahsi T, Erdem HB. Spectrum of BRCA1/BRCA2 variants in 1419 Turkish breast and ovarian cancer patients: a single center study. Turkish Journal of Biochemistry 2020; 45(1):83-90.
- 26. Eccles B, Copson E, Maishman T, Abraham J, Eccles D. Understanding of BRCA VUS genetic results by breast cancer specialists. BMC cancer 2015; 15:1-9.
- 27. Jimenez-Sainz J, Jensen RB. Imprecise medicine: BRCA2 variants of uncertain significance (VUS), the challenges and benefits to integrate a functional assay workflow with clinical decision rules. Genes 2021; 12(5):780.
- 28. Yost S, Ruark E, Alexandrov LB, Rahman N. Insights into BRCA cancer predisposition from integrated germline and somatic analyses in 7632 cancers. JNCI Cancer Spectrum 2019; 3(2):pkz028.
- 29. Culver JO, Brinkerhoff C, Clague J, Yang K, Singh K, Sand S. Variants of uncertain significance in BRCA testing: evaluation of surgical decisions, risk perception, and cancer distress. Clinical genetics 2013; 84(5):464-72.
- 30. Chern J-Y, Lee SS, Frey MK, Lee J, Blank SV. The influence of BRCA variants of unknown significance on cancer risk management decision-making. Journal of gynecologic oncology 2019; 30(4).
- 31. Adam F, Fluri M, Scherz A, Rabaglio M. Occurrence of variants of unknown clinical significance in genetic testing for hereditary breast and ovarian cancer syndrome and Lynch syndrome: a literature review and analytical observational retrospective cohort study. BMC medical genomics 2023; 16(1):7.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Kanser Genetiği |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Erken Görünüm Tarihi | 22 Mayıs 2025 |
| Yayımlanma Tarihi | 28 Mayıs 2025 |
| Gönderilme Tarihi | 16 Mayıs 2024 |
| Kabul Tarihi | 28 Ekim 2024 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 11 Sayı: 2 |
