Genetic mutations associated with hereditary breast cancer in Nicaraguan women
DOI:
https://doi.org/10.5377/rtu.v10i29.12735Keywords:
Breast cancer, Hereditary, Susceptibility genes, BRCA1/2, Pathogenic variants, Latin AmericaAbstract
Introduction: The etiology of breast cancer is multifactorial; however, it has been shown that most are sporadic and 5 to 10% of genetic origin. Genes known to date, and associated with an inherited predisposition to breast cancer, have been classified into high, moderate and low penetrance genes.
Objective: To determine genetic mutations associated to hereditary breast cancer in Nicaraguan women.
Materials and method: 39 women with histopathological diagnosis of breast cancer were recruited to participate in the study, with prior informed consent. 5ml of peripheral blood was taken from each of the patients for DNA extraction, then the genetic test was performed on the BRCA1, BRCA2, Tp53, PALB2, CDH1, PTEN and CHEK2 genes, determining their clinical significance by comparing the sequences with the databases from the Breast Cancer Information Core (BIC) and ClinVar.
Results: The 10% (4/39) of patients studied carry a pathogenic mutation in the BRCA2 (5%), Tp53 and PALB2 genes (2.5% respectively), associated with hereditary breast cancer. Variations of benign clinical significance, uncertain, variants that have not yet been reported in the databases and others with pathogenicity conflicts were also identified.
Conclusions: It is necessary and important to include molecular diagnosis in Nicaraguan patients at risk of developing hereditary breast cancer, for their own well-being and that of their family members, to achieve an early diagnosis, and to improve therapy and follow-up. Therefore, we recommend integrating genetic screening for Nicaraguan women at risk of developing this disease and for those who already suffer from it.
Downloads
References
Abugattas, J., Llacuachaqui, M., Allende, Y. S., Velásquez, A. A., Velarde, R., Cotrina, J., Garcés, M., León, M., Calderón, G., de la Cruz, M., Mora, P., Royer, R., Herzog, J., Weitzel, J. N., & Narod, S. A. (2015). Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Peru. Clinical genetics, 88(4), 371–375. https://doi.org/10.1111/cge.12505
Adaniel, C., Salinas, F., Donaire, J. M., Bravo, M. E., Peralta, O., Paredes, H., Aliaga, N., Sola, A., Neira, P., Behnke, C., Rodriguez, T., Torres, S., Lopez, F., & Hurtado, C. (2019). Non-BRCA1/2 Variants Detected in a High-Risk Chilean Cohort with a History of Breast and/or Ovarian Cancer. Journal of global oncology, 5, 1–14. https://doi.org/10.1200/JGO.18.00163
Álvarez, C., Tapia, T., Perez-Moreno, E., Gajardo-Meneses, P., Ruiz, C., Rios, M., Missarelli, C., Silva, M., Cruz, A., Matamala, L., Carvajal-Carmona, L., Camus, M., & Carvallo, P. (2017). BRCA1 and BRCA2 founder mutations account for 78% of germline carriers among hereditary breast cancer families in Chile. Oncotarget, 8(43), 74233–74243. https://doi.org/10.18632/oncotarget.18815
Apostolou, P., & Fostira, F. (2013). Hereditary breast cancer: the era of new susceptibility genes. BioMed research international, 2013, 747318. https://doi.org/10.1155/2013/747318
Ashton-Prolla, P., & Vargas, F. R. (2014). Prevalence and impact of founder mutations in hereditary breast cancer in Latin America. Genetics and molecular biology, 37(1 Suppl), 234–240. https://doi.org/10.1590/s1415-47572014000200009
Bagherzadeh, M., Szymiczek, A., Donenberg, T., Butler, R., Hurley, J., Narod, S. A., & Akbari, M. R. (2020). Association of RAD51C germline mutations with breast cancer among Bahamians. Breast cancer research and treatment, 184(2), 649–651. https://doi.org/10.1007/s10549-020-05872-3
Brewer, H. R., Jones, M. E., Schoemaker, M. J., Ashworth, A., & Swerdlow, A. J. (2017). Family history and risk of breast cancer: an analysis accounting for family structure. Breast cancer research and treatment, 165(1), 193–200. https://doi.org/10.1007/s10549-017-4325-2
Buleje, J., Guevara-Fujita, M., Acosta, O., Huaman, F., Danos, P., Murillo, A., Pinto, J. A., Araujo, J. M., Aguilar, A., Ponce, J., Vigil, C., Castaneda, C., Calderon, G., Gomez, H. L., & Fujita, R. (2017). Mutational analysis of BRCA1 and BRCA2 genes in Peruvian families with hereditary breast and ovarian cancer. Molecular genetics & genomic medicine, 5(5), 481–494. https://doi.org/10.1002/mgg3.301
Carraro, D. M., Koike Folgueira, M. A., Garcia Lisboa, B. C., Ribeiro Olivieri, E. H., Vitorino Krepischi, A. C., de Carvalho, A. F., de Carvalho Mota, L. D., Puga, R. D., do Socorro Maciel, M., Michelli, R. A., de Lyra, E. C., Grosso, S. H., Soares, F. A., Achatz, M. I., Brentani, H., Moreira-Filho, C. A., & Brentani, M. M. (2013). Comprehensive analysis of BRCA1, BRCA2 and TP53 germline mutation and tumor characterization: a portrait of early-onset breast cancer in Brazil. PloS one, 8(3), e57581. https://doi.org/10.1371/journal.pone.0057581
Cerretini R, Mercado G, Morganstein J, Schiaffi J, Reynoso M, Montoya D, Valdéz R, Narod SA, Akbari MR. Germline pathogenic variants in BRCA1, BRCA2, PALB2 and RAD51C in breast cancer women from Argentina. Breast Cancer Res Treat. 2019 Dec;178(3):629-636. doi: 10.1007/s10549-019-05411-9. Epub 2019 Aug 24. PMID: 31446535. Accesado el 03 de junio del 2021 en https://pubmed.ncbi.nlm.nih.gov/31446535/
Chávarri-Guerra, Y., Villarreal-Garza, C., Liedke, P. E., Knaul, F., Mohar, A., Finkelstein, D. M., & Goss, P. E. (2012). Breast cancer in Mexico: a growing challenge to health and the health system. The Lancet. Oncology, 13(8), e335–e343. https://doi.org/10.1016/S1470-2045(12)70246-2
Cock-Rada, A. M., Ossa, C. A., Garcia, H. I., & Gomez, L. R. (2018). A multi-gene panel study in hereditary breast and ovarian cancer in Colombia. Familial cancer, 17(1), 23–30. https://doi.org/10.1007/s10689-017-0004-z
da Costa E Silva Carvalho, S., Cury, N. M., Brotto, D. B., de Araujo, L. F., Rosa, R., Texeira, L. A., Plaça, J. R., Marques, A. A., Peronni, K. C., Ruy, P. C., Molfetta, G. A., Moriguti, J. C., Carraro, D. M., Palmero, E. I., Ashton-Prolla, P., de Faria Ferraz, V. E., & Silva, W. A., Jr (2020). Germline variants in DNA repair genes associated with hereditary breast and ovarian cancer syndrome: analysis of a 21 gene panel in the Brazilian population. BMC medical genomics, 13(1), 21. https://doi.org/10.1186/s12920-019-0652-y
Della Valle A, Acevedo C, Esperón P, Neffa F, Artagaveytia N, Santander G, Menini M, Vergara C, Carusso F, Sapone M. Cáncer de mama y ovario hereditario en Uruguay. Rev. Méd. Urug. [Internet]. 16 de julio de 2019 [citado 4 de junio de 2021];33(2):102-7. Disponible en: http://revista.rmu.org.uy/ojsrmu311/index.php/rmu/article/view/112/99
Donenberg, T., Ahmed, H., Royer, R., Zhang, S., Narod, S. A., George, S., Akbari, M. R., Ali, J., & Hurley, J. (2016). A Survey of BRCA1, BRCA2, and PALB2 mutations in women with breast cancer in Trinidad and Tobago. Breast cancer research and treatment, 159(1), 131–138. https://doi.org/10.1007/s10549-016-3870-4
Fernández, A., & Reigosa, A. (2016). Cáncer de mama hereditario. Comunidad y salud. 2016; 14: 1, pp. 52-60
Gallardo-Alvarado, L. N., Tusié-Luna, M. T., Tussié-Luna, M. I., Díaz-Chávez, J., Segura, Y. X., Bargallo-Rocha, E., Villarreal, C., Herrera-Montalvo, L. A., Herrera-Medina, E. M., & Cantu-de Leon, D. F. (2019). Prevalence of germline mutations in the TP53 gene in patients with early-onset breast cancer in the Mexican population. BMC cancer, 19(1), 118. https://doi.org/10.1186/s12885-019-5312-2
García, L., Gutiérrez, G., & Narod, S. Epidemiología descriptiva y genética molecular del cáncer de mama hereditario en Costa Rica. Rev. Biol. Trop. (Int. J. Trop. Biol. ISSN-0034-7744). 2012: Dec; Vol. 60 (4): 1663-1668. Accesado el 04 de junio del 2021 en https://www.scielo.sa.cr/pdf/rbt/v60n4/a23v60n4.pdf
George, S., Donenberg, T., Alexis, C., DeGennaro, V., Jr, Dyer, H., Yin, S., Ali, J., Butler, R., Chin, S. N., Curling, D., Lowe, D., Lunn, J., Turnquest, T., Wharfe, G., Cerbon, D., Barreto-Coelho, P., Schlumbrecht, M. P., Akbari, M. R., Narod, S. A., & Hurley, J. E. (2021). Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean. JAMA network open, 4(3), e210307. https://doi.org/10.1001/jamanetworkopen.2021.0307
Gutiérrez Espeleta, G. A., Llacuachaqui, M., García-Jiménez, L., Aguilar Herrera, M., Loáiciga Vega, K., Ortiz, A., Royer, R., Li, S., & Narod, S. A. (2012). BRCA1 and BRCA2 mutations among familial breast cancer patients from Costa Rica. Clinical genetics, 82(5), 484–488. https://doi.org/10.1111/j.1399-0004.2011.01774.x
Hernández, J. E., Llacuachaqui, M., Palacio, G. V., Figueroa, J. D., Madrid, J., Lema, M., Royer, R., Li, S., Larson, G., Weitzel, J. N., & Narod, S. A. (2014). Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Medellín, Colombia. Hereditary cancer in clinical practice, 12(1), 11. https://doi.org/10.1186/1897-4287-12-11
Jara, L., Morales, S., de Mayo, T., Gonzalez-Hormazabal, P., Carrasco, V., & Godoy, R. (2017). Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations. Biological research, 50(1), 35. https://doi.org/10.1186/s40659-017-0139-2
Lara, K., Consigliere, N., Pérez, J., & Porco, A. (2012). BRCA1 and BRCA2 mutations in breast cancer patients from Venezuela. Biological research, 45(2), 117–130. https://doi.org/10.4067/S0716-97602012000200003
Larsen, M. J., Thomassen, M., Gerdes, A. M., & Kruse, T. A. (2014). Hereditary breast cancer: clinical, pathological and molecular characteristics. Breast cancer: basic and clinical research, 8, 145–155. https://doi.org/10.4137/BCBCR.S18715
Lerner-Ellis, J., Donenberg, T., Ahmed, H., George, S., Wharfe, G., Chin, S., Lowe, D., Royer, R., Zhang, S., Narod, S., Hurley, J., & Akbari, M. R. (2017). A high frequency of PALB2 mutations in Jamaican patients with breast cancer. Breast cancer research and treatment, 162(3), 591–596. https://doi.org/10.1007/s10549-017-4148-1
Mahdavi, M., Nassiri, M., Kooshyar, M. M., Vakili-Azghandi, M., Avan, A., Sandry, R., Pillai, S., Lam, A. K., & Gopalan, V. (2019). Hereditary breast cancer; Genetic penetrance and current status with BRCA. Journal of cellular physiology, 234(5), 5741–5750. https://doi.org/10.1002/jcp.27464
Narod, S., & Rodríguez, A. (2011) Predisposición genética para el cáncer de mama: genes BRCA1 y BRCA2. Salud Publica Mex 2011; 53:420-429
Quezada Urban, R., Díaz Velásquez, C. E., Gitler, R., Rojo Castillo, M. P., Sirota Toporek, M., Figueroa Morales, A., Moreno García, O., García Esquivel, L., Torres Mejía, G., Dean, M., Delgado Enciso, I., Ochoa Díaz López, H., Rodríguez León, F., Jan, V., Garzón Barrientos, V. H., Ruiz Flores, P., Espino Silva, P. K., Haro Santa Cruz, J., Martínez Gregorio, H., Rojas Jiménez, E. A., … Vaca Paniagua, F. (2018). Comprehensive Analysis of Germline Variants in Mexican Patients with Hereditary Breast and Ovarian Cancer Susceptibility. Cancers, 10(10), 361. https://doi.org/10.3390/cancers10100361
Rebbeck, T. R., Friebel, T. M., Friedman, E., Hamann, U., Huo, D., Kwong, A., Olah, E., Olopade, O. I., Solano, A. R., Teo, S. H., Thomassen, M., Weitzel, J. N., Chan, T. L., Couch, F. J., Goldgar, D. E., Kruse, T. A., Palmero, E. I., Park, S. K., Torres, D., van Rensburg, E. J., … Nathanson, K. L. (2018). Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2mutations. Human mutation, 39(5), 593–620.
Solano, A. R., Aceto, G. M., Delettieres, D., Veschi, S., Neuman, M. I., Alonso, E., Chialina, S., Chacón, R. D., Renato, M. C., & Podestá, E. J. (2012). BRCA1 And BRCA2 analysis of Argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin. SpringerPlus, 1, 20. https://doi.org/10.1186/2193-1801-1-20
Torres, D., Bermejo, J. L., Rashid, M. U., Briceño, I., Gil, F., Beltran, A., Ariza, V., & Hamann, U. (2017). Prevalence and Penetrance of BRCA1 and BRCA2 Germline Mutations in Colombian Breast Cancer Patients. Scientific reports, 7(1), 4713. https://doi.org/10.1038/s41598-017-05056-y
Torres-Mejía, G., Royer, R., Llacuachaqui, M., Akbari, M. R., Giuliano, A. R., Martínez-Matsushita, L., Angeles-Llerenas, A., Ortega-Olvera, C., Ziv, E., Lazcano-Ponce, E., Phelan, C. M., & Narod, S. A. (2015). Recurrent BRCA1 and BRCA2 mutations in Mexican women with breast cancer. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 24(3), 498–505. https://doi.org/10.1158/1055-9965.EPI-13-0980
Tung, N., Lin, N. U., Kidd, J., Allen, B. A., Singh, N., Wenstrup, R. J., Hartman, A. R., Winer, E. P., & Garber, J. E. (2016). Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients with Breast Cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 34(13), 1460–1468. https://doi.org/10.1200/JCO.2015.65.0747
Vaca-Paniagua F, Álvarez-Gómez RM, Fragoso-Ontiveros V, Vidal-Millan S, Herrera LA, et al. (2012) Full-Exon Pyrosequencing Screening of BRCA Germline Mutations in Mexican Women with Inherited Breast and Ovarian Cancer. PLoS ONE 7(5): e37432. doi: 10.1371/journal.pone.0037432
Villarreal-Garza, C., Aguila, C., Magallanes-Hoyos, M. C., Mohar, A., Bargalló, E., Meneses, A., Cazap, E., Gomez, H., López-Carrillo, L., Chávarri-Guerra, Y., Murillo, R., & Barrios, C. (2013). Breast cancer in young women in Latin America: an unmet, growing burden. The oncologist, 18(12), 1298–1306. https://doi.org/10.1634/theoncologist.2013-0321
Villarreal-Garza, C., Alvarez-Gómez, R. M., Pérez-Plasencia, C., Herrera, L. A., Herzog, J., Castillo, D., Mohar, A., Castro, C., Gallardo, L. N., Gallardo, D., Santibáñez, M., Blazer, K. R., & Weitzel, J. N. (2015). Significant clinical impact of recurrent BRCA1 and BRCA2 mutations in Mexico. Cancer, 121(3), 372–378. https://doi.org/10.1002/cncr.29058
Villarreal-Garza, C., Weitzel, J. N., Llacuachaqui, M., Sifuentes, E., Magallanes-Hoyos, M. C., Gallardo, L., Alvarez-Gómez, R. M., Herzog, J., Castillo, D., Royer, R., Akbari, M., Lara-Medina, F., Herrera, L. A., Mohar, A., & Narod, S. A. (2015). The prevalence of BRCA1 and BRCA2 mutations among young Mexican women with triple-negative breast cancer. Breast cancer research and treatment, 150(2), 389–394. https://doi.org/10.1007/s10549-015-3312-8
Walsh, M. F., Nathanson, K. L., Couch, F. J., & Offit, K. (2016). Genomic Biomarkers for Breast Cancer Risk. Advances in experimental medicine and biology, 882, 1–32. https://doi.org/10.1007/978-3-319-22909-6_1
Weitzel, J. N., Clague, J., Martir-Negron, A., Ogaz, R., Herzog, J., Ricker, C., Jungbluth, C., Cina, C., Duncan, P., Unzeitig, G., Saldivar, J. S., Beattie, M., Feldman, N., Sand, S., Port, D., Barragan, D. I., John, E. M., Neuhausen, S. L., & Larson, G. P. (2013). Prevalence and type of BRCA mutations in Hispanics undergoing genetic cancer risk assessment in the southwestern United States: a report from the Clinical Cancer Genetics Community Research Network. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 31(2), 210–216. https://doi.org/10.1200/JCO.2011.41.0027
Wendt, C., & Margolin, S. (2019). Identifying breast cancer susceptibility genes - a review of the genetic background in familial breast cancer. Acta oncologica (Stockholm, Sweden), 58(2), 135–146. https://doi.org/10.1080/0284186X.2018.1529428
Zavala, V. A., Serrano-Gomez, S. J., Dutil, J., & Fejerman, L. (2019). Genetic Epidemiology of Breast Cancer in Latin America. Genes, 10(2), 153. https://doi.org/10.3390/genes10020153
Zayas-Villanueva OA, Campos-Acevedo LD, Lugo-Trampe JJ, Hernández-Barajas D, González-Guerrero JF, Noriega-Iriondo MF, Ramírez-Sánchez IA, Martínez-de-Villarreal LE. Analysis of the pathogenic variants of BRCA1 and BRCA2 using next-generation sequencing in women with familial breast cancer: a case-control study. BMC Cancer. 2019 Jul 22;19(1):722. doi: 10.1186/s12885-019-5950-4. PMID: 31331294; PMCID: PMC6647062. Acceso el 29 de mayo del 2021 en https://pubmed.ncbi.nlm.nih.gov/31331294/
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Universidad Nacional Autónoma de Nicaragua, Managua
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Los autores que publican en esta revista están de acuerdo con los siguientes términos.
- El autor o los autores de los artículos, ensayos o investigaciones conceden a la Universidad Nacional Autónoma de Nicaragua, Managua (UNAN-Managua) los derechos de edición (copyright) del trabajo enviado, por consiguiente la Universidad cuenta con el derecho exclusivo para publicar el artículo durante el periodo completo de los derechos de autor.
- Estos derechos de autor/ autores autorizan a la Revista Torreón Universitario y a la Universidad editar y divulgar/publicar el artículo en dicha Revista, incluyendo reproducción impresa y electrónica, el almacenamiento, recuperación y cualquier otro tipo de publicación, y fuentes de información secundaria como servicios de resúmenes y bases de datos, así mismo la facultan a proteger el artículo contra el uso no autorizado para su difusión por medios impresos o electrónicos (PDF, HTML, EPUB, XML u otros).
Licencia para el uso del contenido
La revista hace uso de la Licencia Creative Commons Atribución-NoComercial-SinDerivar 4.0 Internacional.
Bajo esta declaración:
Este revista está sujeta a una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional. Puede ser copiada, distribuida y transmitida públicamente siempre y cuando se cite al autor y la fuente (Revista Torreón Universitario), no debe modificarse ni utilizarse con ningún fin comercial. La licencia completa se puede consultar en http://creativecommons.org/licenses/by-nc-nd/4.0/.
