Frequency of sequence mutations and variants for the BRCA1 and BRCA2 genes in a sample of Colombian women with suspected hereditary breast cancer syndrome: Case series
DOI:
https://doi.org/10.18597/rcog.294Keywords:
Breast cancer, BRCA 1, BRCA 2, gene mutationAbstract
Objective: To describe sequence variants in the BRCA1 and BRCA2 genes in a sample of Colombian patients with a personal or family history of breast cancer suggestive of genetic risk.
Materials and methods: Case series consisting of 67 patients referred for genetic testing because of suspected hereditary breast and ovarian cancer syndrome (HBOC). Of the 67 cases, 42 (62.7%) met the medical indication criteria of the 2013 National Comprehensive Cancer Network (NCCN) and they were subjected to the entire sequencing of the BRCA1 and BRCA2 genes. A determination was made of the frequency of sequence mutation, variants, and of the clinical significance of the variants found based on the Breast Cancer Information Core (BIC).
Results: Mutations were identified for the BRCA 1 gene in six patients (14.3%), no mutation was documented for the BRCA 2 gene, and 43 genetic variants were found in 27 patients (64.2% of 42 cases). Of these, 21 (48.8%) were identified in the BRCA1 gene and 22 (51.2%) in the BRCA 2 gene. Among these variants, 5 pathogenic mutations were found only in the BRCA1 gene and, of those, only 1 had been reported previously in Colombia.
Conclusions: This study identifies pathogenic genetic variants in the BRCA1 gene not described previously in the Colombian population, as well as others known in different populations. Therefore, it helps expand knowledge regarding the variants of the BRCA1 and BRCA2 genes in the Colombian population. However, additional studies are required with sufficient power and methodological quality to estimate the frequency of sequence mutations and variants for the BRCA1 and BRCA2 genes in Colombian women suspected of having the hereditary breast or ovarian cancer syndrome.
Author Biographies
Juan Felipe Arias-Blanco
Eder Alonso Ospino-Durán
Carlos M. Restrepo-Fernández
Luis Guzmán-AbiSaab
Dora Janeth Fonseca-Mendoza
Diana Isabel Ángel-Guevara
Elena del Pilar Garzón-Venegas
Oscar Gamboa-Garay
Alexandra J. Obregón-Tito
Yenny Gómez-Parrado
References
Piñeros M, Gamboa O, Hernández-Suárez G, Pardo C, Bray F. Patterns and trends in cancer mortality in Colombia 1984-2008. Cancer epidemiol. 2013;37:233-9.
Piñeros M, Sánchez R, Perry F, García OA, Ocampo R, Cendales R. Delay for diagnosis and treatment of breast cancer in Bogota, Colombia. Salud Pública Mex. 2011:478-85.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11-30.
Nkondjock A, Ghadirian P. Epidemiology of breast cancer among BRCA mutation carriers: an overview. Cancer Lett. 2004;205:1-8.
Walsha T, Leea MK, Casadeia S, Thorntona AM, Straya SM, Pennil C, et al. Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proceedings of the National Academy of Sciences. 2010;107:12629-33.
Meaney-Delman D, Bellcross C. Hereditary breast/ovarian cancer syndrome: a primer for obstetricians/gynecologists Obstet Gynecol Clin North Am. 2013;40:475-512.
Yoshida K, Yoshio M. Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage. Cancer Sci. 2004; 95: 866-71.
Green VL. Breast cancer risk assessment, prevention, and the future. Obstet Gynecol Clin North Am. 2013;40:525-49.
National Comprehensive Cancer Network. Genetic/familial high-risk assessment: breast and ovarian (version 1.2013). Rockledge, PA: NCCN Clinical Practice Guidelines in Oncology; 2013.
Gallardo M, Silva A, Rubio L, Alvarez C, Torrealba C, Salinas M, et al. Incidence of BRCA1 and BRCA2 mutations in 54 Chilean families with breast/ovarian cancer, genotype–phenotype correlations. Breast Cancer Res Treat. 2006;95:81-7.
Ruiz-Flores P, Sinilnikova OM, Badzioch M, Calderon-Garcidueñas AL, Chopin S, Fabrice O, et al. BRCA1 and BRCA2 mutation analysis of early–onset and familial breast cancer cases in Mexico. Hum Mutat. 2002;20:474-5.
Dutil J, Colon-Colon JL, Matta JL, Sutphen R, Echenique M. Identification of the prevalent BRCA1 and BRCA2 mutations in the female population of Puerto Rico. Cancer Genet. 2012;205:242-8.
Esteves VF, Thuler LC, Amêndola LC, Koifman RJ, Koifman S, Frankel PP, et al. Prevalence of BRCA1 and BRCA2 gene mutations in families with medium and high risk of breast and ovarian cancer in Brazil. Braz J Med Biol Res. 2009;42:453-7.
Weitzel JN, Clague J, Martir-Negron A, Ogaz R, Herzog J, Ricker C, et al. 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. J Clin Oncol. 2013;31:210-6.
Sanabria MC, Muñoz G, Vargas CI. Análisis de las mutaciones más frecuentes del gen BRCA1 (185delAG y 5382insC) en mujeres con cáncer de mama en Bucaramanga, Colombia. Biomédica. 2009;29:61-72.
Torres D, Rashid MU, Gil F, Umana A, Ramelli G, Robledo JF, et al. High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia. Breast Cancer Res Treat. 2007;103:225-32.
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.
Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci. 1977;74:5463-7.
Ensembl, NCBI and UCSC browsers/annotation groups. Browser Genome Release Agreement. Reino Unido (UK). [Visitado 2015 Sept 15]. Disponible en: http://www.ensembl.org/Homo_sapiens/Gene
Porchia LM, González M, Calderilla L, Ordaz NI, Islas F, Oldak J, et al. Common BRCA1 and BRCA2 Mutations among Latin American Breast Cancer Subjects: A Meta-Analysis. J Carcinog. 2015;6:228.
Roa BB, Boyd AA, Volcik K, Richards CS. Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat Genet. 1996;14:185-7.
Hernández JE, Llacuachaqui M, Palacio GV, Figueroa JD, Madrid J, Lema M, et al. Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Medellin, Colombia. Hered Cancer Clin Pract. 2014;12:11.
Castéra L, Krieger S, Rousselin A, Legros A, Baumann JJ, Bruet O, et al. Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes. Eur J Hum Genet. 2014;22:1305-13.
Lindor NM, Goldgar DE, Tavtigian SV, Plon SE, Couch FJ. BRCA1/2 Sequence variants of uncertain significance: a primer for providers to assist in discussions and in medical management. Oncologist. 2013;18:518-24.
How to Cite
Downloads
Downloads
Published
Issue
Section
| Article metrics | |
|---|---|
| Abstract views | |
| Galley vies | |
| PDF Views | |
| HTML views | |
| Other views | |
