Mutational spectrum in breast cancer associated BRCA1 and BRCA2 genes in Colombia
Abstract
Introduction: The risk of developing breast and ovarian cancer is higher in families that carry mutations in BRCA1 or BRCA2 genes, and timely mutation detection is critical.Objective: To identify the presence of mutations in the Colombian population and evaluate two testing strategies.Methods: From a total universe of 853 individual blood samples tests referred for BRCA1 and BRCA2 typing, 256 cases were analyzed by complete direct sequencing of both genes in Myriad Genetics, and the remaining 597 cases were studied by partial sequencing based on founder mutations in a PCR test designed by ourselves ("Profile Colombia").Results: We found 107 patients carrying deleterious mutations in this group of patients, 69 (64.5%) located in BRCA1, and 38 (35.5%) in BRCA2. Overall, we detected 39 previously unreported mutations in Colombia (22 in BRCA1 and 17 in BRCA2) and only 4 out of the 6 previously reported founder mutations. Sixty four out of 597 patients (10.7%) studied by "Profile Colombia" showed mutations in BRCA1 or BRCA2, and 41/256 patients (16%) showed mutations by complete BRCA1-BRCA2 sequencing.Conclusions: The spectrum of 44 different mutations in Colombia as detected in our study is broader than the one previously reported for this country. "Profile Colombia" is a useful screening test to establish both founder and new mutations (detection rate of 10.7%) in cases with family history of breast cancer. Complete sequencing shows a detection rate of 16.0%, and should complement the study of the genetic basis of this disease.Authors
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Keywords
- Breast cancer
- BRCA1
- BRCA2
- mutation
- diagnostic test
- Colombia
References
. Globocan (IARC). Breast cancer: Estimated Incidence, Mortality and Prevalence Worldwide in 2012. IARC Monogr Eval Carcinog Risks Hum. 2012.
. Nkondjock A, Ghadirian P. Epidemiology of breast cancer among BRCA mutation carriers: an overview. Cancer lett. 2004; 205: 1-8.
. Londoño B., Ramírez C.M, Urquijo L.E, Ospino M.L, Londoño C., Ortiz L.C et al. Plan nacional para el control de cáncer en Colombia 2012-2020. Republica de Colombia, Ministerio de Salud y Protección Social / Instituto Nacional de Cancerología. 2012.
. Piñeros M., Sánchez R., Perry F., García O.A, Ocampo R., Cendales R. Demoras en el diagnóstico y tratamiento de mujeres con cáncer de mama en Bogotá, Colombia. Salud Publica Mex. 2011; 53: 478-485.
. Universidad del Valle. Registro poblacional de cáncer de Cali, Colombia. Tasas de mortalidad media anual específicas por edad, crudas y estandarizadas por edad por 100.000 por año en mujeres (2008-2012). Available in: http://rpcc.univalle.edu.co/es/Mortalidad/Estadisticas/Tablas_mortalidad.php?periodo=10&genero=2
. Universidad del Valle. Registro poblacional de cáncer de Cali, Colombia. Tasas de Incidencia media anual específicas por edad, crudas y estandarizadas por edad por 100.000 por año en mujeres (2004-2008). Available in: http://rpcc.univalle.edu.co/es/incidencias/Estadisticas/Tablas_Incidencia.php?periodo=16&genero=2
. Briceño I, Torres D. Cáncer familiar. In: Tratado de Medicina Interna. 4, Colombia: Celsus; 2005. 22-26.
. Torres D, Rashid M.U, 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: 225-232.
. Struewing J.P, Hartge P, Wacholder S, Baker S.M, Berlin M., McAdams M., et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews, N. Engl. J. Med. 1997; 336: 1401 – 1408.
. Easton D.F, Steele L., Fields P., Ormiston W, Averill D., Daly P.A et al. Cancer risks in two large breast cancer families linked to BRCA2 on chromosome 13q12-13, Am. J. Hum. Genet. 1997; 61: 120-128.
. Finger A., Irmin L., Geva R., Flex D., Sulkes J., Sulkes A. et al. The rate of the 6174delT founder Jewish mutation in BRCA2 in patients with non-colonic gastrointestinal tract tumours in Israel. Br. J. Cancer. 2001; 84: 478 – 481.
. Ghadirian P., Narod S., Perret C., Lambert D.M, Latreille J, Letendre F. et al., Hereditary breast cancer in 19 females and 2 males: Kindred, P.G. 1940, Eur. J. Cancer. 1995; 31A: 284-287.
. Chodosh LA. Expression of BRCA1 and BRCA2 in normal and neoplastic cells.
J Mammary Gland Biol Neoplasia. 1998; 3(4): 389-402.
. Hall J.M, Lee M.K, Newman B, Morrow J.E, Anderson L.A, Huey B, King M.C. Linkage of early-onset familial breast cancer to chromosome 17q21. Science. 1990; 250(4988): 1684-9.
. Wooster R, Bignell G, Lancaster J, Swift S, Seal Sh, Mangion J et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995; 378: 789-792.
. Tavtigian SV, Simard J, Rommens J, Couch F, Shattuck-Eidens D, Neuhausen S, et al. The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet. 1996; 12(3):333-7.
. Fergus J. Couch et al. BRCA2 germline mutations in male breast cancer cases and breast cancer families, Nat Genet. 1996; 13: 123-125.
. Torres D, Umaña A, Robledo JF, Caicedo JJ, Quintero E, Orozco A et al. Estudio de factores genéticos para cáncer de mama en Colombia. Univ Med. 2009; 50(3): 297–301
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