GENETIC PREDISPOSITION TO CANCER: REPORT OF THE FIRST CASE IN PERU OF THE 657DEL5 VARIANT IN THE NBN GENE
Main Article Content
Abstract
Background: Breast cancer has well known genetic mutations affecting the DNA-damage repair mechanism and predispose for the development of the disease. The heterozygous pathogenic variants found in the NBN gene has been linked to a higher likelihood of developing cancer;
Methods: clinical description of 3 cases and review of the literature;
Results: We describe a family cluster of 3 sisters affected by different cancer types. One of them had a breast cancer associated to the 657del5 pathogenic variant in the NBN gene and was handled with breast conserving therapy. Another had bilateral breast cancer and the third one had endometrial cancer;
Conclusions: Breast cancer associated with the 657del5 pathogenic variant in the NBN gene has been described in various publications, mainly in populations other than Peru.
Keywords:
NBN mutation, breast cancer, endometrial cancer, genetic breast cancer
Article Details
How to Cite
MEZA-GARCIA, Karoll et al.
GENETIC PREDISPOSITION TO CANCER: REPORT OF THE FIRST CASE IN PERU OF THE 657DEL5 VARIANT IN THE NBN GENE.
Medical Research Archives, [S.l.], v. 11, n. 6, june 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3790>. Date accessed: 22 dec. 2024.
doi: https://doi.org/10.18103/mra.v11i6.3790.
Section
Case Reports
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Estimated age-standardized incidence and mortality rates (World) in 2020, World, females, all ages (excl. NMSC). GLOBOCAN 2020. Accessed March 10, 2023. https://gco.iarc.fr/.
2. Hung C; Huang H; Hung C; Moi S. Identification of Candidate Genes in Early-Stage Invasive Ductal Carcinoma Patients with High-Risk Mortality Using Genes Commonly Involved in Breast Cancer: A Retrospective Study. Public Health Genomics. 2022; 25:32–41.
3. Uzunoglu H; Korak T; Ergul E; Uren N; Uren N; Sazci A. Association of the nibrin gene (NBN) variants with breast cancer. Biomed Rep. 2016; 4(3): 369–373.
4. Varon R, Demuth I, Chrzanowska K. GeneReviews. Nijmegen Breakage Syndrome. 2022. Accessed January 10, 2023: https://www.ncbi.nlm.nih.gov/books/NBK1176/
5. Zuntini R; Bonora E; Pradella L; Benedetta L; Vidone M; De Fanti S. Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next?. Int. J. Mol. Sci. 2021, 22: 5832. Accessed February 18, 2023. https://doi.org/10.3390/ijms22115832.
6. Desjardins, S., Beauparlant, J., Labrie, Y. et al. Variations in the NBN/NBS1 gene and the risk of breast cancer in non-BRCA1/2French Canadian families with high risk of breast cancer. BMC Cancer. 2009, 181(9). Accessed February 10, 2023. https://doi.org/10.1186/1471-2407-9-181.
7. Nithya, P., ChandraSekar, A. NBN Gene Analysis and its Impact on Breast Cancer. J Med Syst. 2019; 43 (8): 270. Accessed February 1, 2023. https://doi.org/10.1007/s10916-019-1328-z
8. Hsu H, Wang H, Chen S, Hsu G, Shen C, Yu J. Breast cancer risk is associated with the genes encoding the DNA double-strand break repair Mre11/Rad50/Nbs1 complex. Cancer Epidemiol Biomarkers Prev. 2007;16 (10):2024–2032. doi: 10.1158/1055-9965.EPI-07-0116.
9. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. Version 1.2020. 2019.
10. Zhang G, Zeng Y, Liu Z, Wei W. Significant association between Nijmegen breakage syndrome 1 657del5 polymorphism and breast cancer risk. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine. 2013; 34(5):2753-2757.
11. Cybulski C; Kluźniak W; Huzarski T; Wokołorczyk D; Kashyap A; Rusak B; et.al. The spectrum of mutations predisposing to familial breast cancer in Poland. Int. J. Cancer. 2019; 145: 3311–3320
12. Chrzanowska K. H., Gregorek H., Dembowska-Bagińska B., Kalina M. A., Digweed M. Nijmegen breakage syndrome (NBS) Orphanet Journal of Rare Diseases. 2012; 7(13). doi: 10.1186/1750-1172-7-13.
13. Seemanová E., Jarolim P., Seeman P., et al. Cancer risk of heterozygotes with the NBN founder mutation. Journal of the National Cancer Institute. 2007; 99(24):1875–1880. doi: 10.1093/jnci/djm251.
14. Piombino C, Cortesi L, Lambertini M, et al. "Secondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA", Journal of Oncology. 2020, Article ID 6384190. https://doi.org/10.1155/2020/6384190
15. Gao P, Ma N, Li M, Tian Q, Liu D. Functional variants in NBS1 and cancer risk: evidence from a meta-analysis of 60 publications with 111 individual studies. Mutagenesis. 2013; 28(6):683-97. doi: 10.1093/mutage/get048.
16. Borecka M, Zemankova P, Lhota F, Soukupova J, Kleiblova P, Vocka M, Soucek P, Ticha I, Kleibl Z, Janatova M. The c.657del5 variant in the NBN gene predisposes to pancreatic cancer. Gene. 2016; 587(2):169-72. doi: 10.1016/j.gene.2016.04.056.
17. De la Cruz Ku, G., Karamchandani, M., Chambergo-Michilot, D. et al. Does Breast-Conserving Surgery with Radiotherapy have a Better Survival than Mastectomy? A Meta-Analysis of More than 1,500,000 Patients. Ann Surg Oncol. 2022, 29(10): 6163–6188. https://doi.org/10.1245/s10434-022-12133-8
18. Christiansen, Peer; Mele, Marco; Bodilsen, Anne; Rocco, Nicola; Zachariae, Robert. Breast-Conserving Surgery or Mastectomy?: Impact on Survival. Annals of Surgery Open. 2022, 3(4): 205. doi: 10.1097/AS9.0000000000000205
19. Kurian A, Hughes E, Handorf E, et al. Breast and ovarian cancer penetrance estimates derived from germline multiple-gene sequencing results in women. JCO Precision Oncology. 2017(1):1-12. Accessed November 12, 2022. http://ascopubs.org/doi/abs/10.1200/PO.16.00066
20. Suszynska M, Klonowska K, Jasinska AJ, Kozlowski P. Large-scale meta-analysis of mutations identified in panels of breast/ovarian cancerrelated genes - providing evidence of cancer predisposition genes. Gynecol Oncol. 2019; 153(2):452-462. Accessed December 18, 2022. https://www.ncbi.nlm.nih.gov/pubmed/30733081
21. Kurian A, Ward K, Howlader N, et al. Genetic testing and results in a population-based cohort of breast cancer patients and ovarian cancer patients. J Clin Oncol 2019;37(15):1305-1315. Accessed December 7, 2022. https://www.ncbi.nlm.nih.gov/pubmed/30964716.
22. NCCN Guidelines Version 2.2023 Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. Cancer Risk Management Based on Genetic Test Results. 2023. Accessed December 29, 2022. https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf
23. Couch F, Shimelis H, Hu C, et al. Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol. 2017;3(9):1190-1196. Accessed December 21, 2022. https://www.ncbi.nlm.nih.gov/pubmed/28418444.
24. Zhang B, Beeghly-Fadiel A, Long J, Zheng W. Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence. Lancet Oncol. 2011;12(5):477-488. Accessed January 15, 2023. https://www.ncbi.nlm.nih.gov/pubmed/21514219
25. Zhang G, Zeng Y, Liu Z, Wei W. Significant association between Nijmegen breakage syndrome 1 657del5 polymorphism and breast cancer risk. Tumour Biol. 2013;34(5):2753-2757. Accessed November 24, 2022. https://www.ncbi.nlm.nih.gov/pubmed/23765759 Breast Cancer Association Consortium, Dorling L, Carvalho S, et al. Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. N Engl J Med. 2021;384(5): 428-439. Accessed December 10, 2022. https://www.ncbi.nlm.nih.gov/pubmed/33471991
26. Hu C, Hart S, Gnanaolivu R, et al. Population-Based Study of Genes Previously Implicated in Breast Cancer. N Engl J Med. 2021;384(5):440-451. doi: 10.1056/NEJMoa2005936.
2. Hung C; Huang H; Hung C; Moi S. Identification of Candidate Genes in Early-Stage Invasive Ductal Carcinoma Patients with High-Risk Mortality Using Genes Commonly Involved in Breast Cancer: A Retrospective Study. Public Health Genomics. 2022; 25:32–41.
3. Uzunoglu H; Korak T; Ergul E; Uren N; Uren N; Sazci A. Association of the nibrin gene (NBN) variants with breast cancer. Biomed Rep. 2016; 4(3): 369–373.
4. Varon R, Demuth I, Chrzanowska K. GeneReviews. Nijmegen Breakage Syndrome. 2022. Accessed January 10, 2023: https://www.ncbi.nlm.nih.gov/books/NBK1176/
5. Zuntini R; Bonora E; Pradella L; Benedetta L; Vidone M; De Fanti S. Detecting Variants in the NBN Gene While Testing for Hereditary Breast Cancer: What to Do Next?. Int. J. Mol. Sci. 2021, 22: 5832. Accessed February 18, 2023. https://doi.org/10.3390/ijms22115832.
6. Desjardins, S., Beauparlant, J., Labrie, Y. et al. Variations in the NBN/NBS1 gene and the risk of breast cancer in non-BRCA1/2French Canadian families with high risk of breast cancer. BMC Cancer. 2009, 181(9). Accessed February 10, 2023. https://doi.org/10.1186/1471-2407-9-181.
7. Nithya, P., ChandraSekar, A. NBN Gene Analysis and its Impact on Breast Cancer. J Med Syst. 2019; 43 (8): 270. Accessed February 1, 2023. https://doi.org/10.1007/s10916-019-1328-z
8. Hsu H, Wang H, Chen S, Hsu G, Shen C, Yu J. Breast cancer risk is associated with the genes encoding the DNA double-strand break repair Mre11/Rad50/Nbs1 complex. Cancer Epidemiol Biomarkers Prev. 2007;16 (10):2024–2032. doi: 10.1158/1055-9965.EPI-07-0116.
9. NCCN Clinical Practice Guidelines in Oncology®: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. Version 1.2020. 2019.
10. Zhang G, Zeng Y, Liu Z, Wei W. Significant association between Nijmegen breakage syndrome 1 657del5 polymorphism and breast cancer risk. Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine. 2013; 34(5):2753-2757.
11. Cybulski C; Kluźniak W; Huzarski T; Wokołorczyk D; Kashyap A; Rusak B; et.al. The spectrum of mutations predisposing to familial breast cancer in Poland. Int. J. Cancer. 2019; 145: 3311–3320
12. Chrzanowska K. H., Gregorek H., Dembowska-Bagińska B., Kalina M. A., Digweed M. Nijmegen breakage syndrome (NBS) Orphanet Journal of Rare Diseases. 2012; 7(13). doi: 10.1186/1750-1172-7-13.
13. Seemanová E., Jarolim P., Seeman P., et al. Cancer risk of heterozygotes with the NBN founder mutation. Journal of the National Cancer Institute. 2007; 99(24):1875–1880. doi: 10.1093/jnci/djm251.
14. Piombino C, Cortesi L, Lambertini M, et al. "Secondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA", Journal of Oncology. 2020, Article ID 6384190. https://doi.org/10.1155/2020/6384190
15. Gao P, Ma N, Li M, Tian Q, Liu D. Functional variants in NBS1 and cancer risk: evidence from a meta-analysis of 60 publications with 111 individual studies. Mutagenesis. 2013; 28(6):683-97. doi: 10.1093/mutage/get048.
16. Borecka M, Zemankova P, Lhota F, Soukupova J, Kleiblova P, Vocka M, Soucek P, Ticha I, Kleibl Z, Janatova M. The c.657del5 variant in the NBN gene predisposes to pancreatic cancer. Gene. 2016; 587(2):169-72. doi: 10.1016/j.gene.2016.04.056.
17. De la Cruz Ku, G., Karamchandani, M., Chambergo-Michilot, D. et al. Does Breast-Conserving Surgery with Radiotherapy have a Better Survival than Mastectomy? A Meta-Analysis of More than 1,500,000 Patients. Ann Surg Oncol. 2022, 29(10): 6163–6188. https://doi.org/10.1245/s10434-022-12133-8
18. Christiansen, Peer; Mele, Marco; Bodilsen, Anne; Rocco, Nicola; Zachariae, Robert. Breast-Conserving Surgery or Mastectomy?: Impact on Survival. Annals of Surgery Open. 2022, 3(4): 205. doi: 10.1097/AS9.0000000000000205
19. Kurian A, Hughes E, Handorf E, et al. Breast and ovarian cancer penetrance estimates derived from germline multiple-gene sequencing results in women. JCO Precision Oncology. 2017(1):1-12. Accessed November 12, 2022. http://ascopubs.org/doi/abs/10.1200/PO.16.00066
20. Suszynska M, Klonowska K, Jasinska AJ, Kozlowski P. Large-scale meta-analysis of mutations identified in panels of breast/ovarian cancerrelated genes - providing evidence of cancer predisposition genes. Gynecol Oncol. 2019; 153(2):452-462. Accessed December 18, 2022. https://www.ncbi.nlm.nih.gov/pubmed/30733081
21. Kurian A, Ward K, Howlader N, et al. Genetic testing and results in a population-based cohort of breast cancer patients and ovarian cancer patients. J Clin Oncol 2019;37(15):1305-1315. Accessed December 7, 2022. https://www.ncbi.nlm.nih.gov/pubmed/30964716.
22. NCCN Guidelines Version 2.2023 Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. Cancer Risk Management Based on Genetic Test Results. 2023. Accessed December 29, 2022. https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf
23. Couch F, Shimelis H, Hu C, et al. Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol. 2017;3(9):1190-1196. Accessed December 21, 2022. https://www.ncbi.nlm.nih.gov/pubmed/28418444.
24. Zhang B, Beeghly-Fadiel A, Long J, Zheng W. Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence. Lancet Oncol. 2011;12(5):477-488. Accessed January 15, 2023. https://www.ncbi.nlm.nih.gov/pubmed/21514219
25. Zhang G, Zeng Y, Liu Z, Wei W. Significant association between Nijmegen breakage syndrome 1 657del5 polymorphism and breast cancer risk. Tumour Biol. 2013;34(5):2753-2757. Accessed November 24, 2022. https://www.ncbi.nlm.nih.gov/pubmed/23765759 Breast Cancer Association Consortium, Dorling L, Carvalho S, et al. Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. N Engl J Med. 2021;384(5): 428-439. Accessed December 10, 2022. https://www.ncbi.nlm.nih.gov/pubmed/33471991
26. Hu C, Hart S, Gnanaolivu R, et al. Population-Based Study of Genes Previously Implicated in Breast Cancer. N Engl J Med. 2021;384(5):440-451. doi: 10.1056/NEJMoa2005936.