Haplotype analysis of the internationally distributed BRCA1 c.3331_3334delCAAG founder mutation reveals a common ancestral origin in Iberia.

BACKGROUND: The BRCA1 c.3331_3334delCAAG founder mutation has been reported in hereditary breast and ovarian cancer families from multiple Hispanic groups. We aimed to evaluate BRCA1 c.3331_3334delCAAG haplotype diversity in cases of European, African, and Latin American ancestry. METHODS: BC mutation carrier cases from Colombia (n = 32), Spain (n = 13), Portugal (n = 2), Chile (n = 10), Africa (n = 1), and Brazil (n = 2) were genotyped with the genome-wide single nucleotide polymorphism (SNP) arrays to evaluate haplotype diversity around BRCA1 c.3331_3334delCAAG. Additional Portuguese (n = 13) and Brazilian (n = 18) BC mutation carriers were genotyped for 15 informative SNPs surrounding BRCA1. Data were phased using SHAPEIT2, and identical by descent regions were determined using BEAGLE and GERMLINE. DMLE+ was used to date the mutation in Colombia and Iberia. RESULTS: The haplotype reconstruction revealed a shared 264.4-kb region among carriers from all six countries. The estimated mutation age was ~ 100 generations in Iberia and that it was introduced to South America early during the European colonization period. CONCLUSIONS: Our results suggest that this mutation originated in Iberia and later introduced to Colombia and South America at the time of Spanish colonization during the early 1500s. We also found that the Colombian mutation carriers had higher European ancestry, at the BRCA1 gene harboring chromosome 17, than controls, which further supported the European origin of the mutation. Understanding founder mutations in diverse populations has implications in implementing cost-effective, ancestry-informed screening.

Sociodemographic, Clinical, and Variation Outcomes for Breast Cancer and Breast Cancer-Related Mutations in a Ten-Year Cohort From Neiva, Huila, Colombia.

Background Some breast cancer cases are related to inherited mutations, and this is the reason why early mutation screening is emerging as an area of focus for cost-effective care. However, breast cancer-related mutations vary according to race, ethnicity, geographic origin, and healthcare access. Surveillance for familial breast cancer is not performed routinely in Colombia. Our main aim in this study was to describe a cohort of breast cancer patients, carrying founder breast cancer gene (BRCA) mutations, which were followed up for up to 10 years (2010-2019) in Neiva, Colombia. Methods We performed a retrospective description from an outpatient care center in Huila, Colombia, a region with high breast cancer rates. This study included patients with both a breast cancer diagnosis and an incident genetic mutation for breast cancer (detected during a breast cancer consultation). We captured information from patient medical records. Descriptive analyses were performed. Results A total of 105 patients met the study's inclusion criteria and were included patients with the BRCA1 mutation and three with BRCA2 mutations. They had a median age of 45 years (IQR, 36 to 51 years). Relatives with a breast cancer history were found in 74 carriers (70.5%). Most patients had a report of Breast Imaging-Reporting and Data System (BIRADS) ≥ 4. A TNM (tumor, node, metastasis) changed reclassification was observed in anatomical vs. prognostic classification. Median follow-up was of 74 months (IQR, 44 to 130), overall observed mortality was 22.9%, and specific mortality was 19.1%. Conclusion Women with breast cancer who carry a mutation related to breast cancer are usually younger than age 50 at diagnosis. Developing strategies and specific policies for this population is needed, and a prevalent BRCA1 c.3331_3334delCAAG mutation could be used as a cost-effective first approach. Among these patients, a risk-increased reclassification was observed.

Risk Factors for Disease Recurrence in Women With Phyllodes Tumors of the Breast in Southern Colombia: A Nine-Year Cohort Study.

Introduction Phyllodes tumors (PTs) are uncommon fibroepithelial breast tumors that occur in middle-aged women, and they tend to vary in biologic behavior. Surgical management is the standard therapy for the condition, but factors associated with recurrence remain unclear. The aim of this study was to evaluate clinical and surgical characteristics related to PT recurrences. Methods This retrospective cohort study included patients in southern Colombia who were diagnosed with PT and managed at a level I teaching and referral hospital over a nine-year period. Factors associated with recurrence were determined by Cox regression analysis. Results This study included 61 patients; their median age was 46 years [interquartile range (IQR): 39-55 years]. Pathologically, 37 tumors (60.7%) were classified as low-grade. The median tumor size was 7 cm (IQR: 4-11.5 cm). Thirty-nine (63.9%) patients underwent quadrantectomy. Nine patients (14.8%) experienced tumor recurrence, with the median time to recurrence being one year (IQR: 0.5-2 years). Distant metastasis was observed in four patients (6.6%) at a median of nine months (IQR: 0.4-2.5 years). Univariate analyses showed that patients with high-grade tumors [hazard ratio (HR): 2.90, p = 0.148] and those who underwent mastectomy (HR: 2.90, p = 0.460) were at higher risk of recurrence. Conclusion PT recurrence may be associated with biological features, the extent of local excision, tumor size, and negative margins. However, multicenter data are needed to confirm these findings.

Breast cancer in six families from Tolima and Huila: BRCA1 3450del4 mutation / [Cáncer de mama en seis familias del Tolima y el Huila: mutación BRCA1 3450del4].

Introduction: Breast cancer is a worldwide public health problem; between 5% and 10% of the cases present familial aggregation explained by genes of high risk such as BRCA1 and BRCA2. The founding origin of the deletion BRCA1 3450del4 in Colombia has been previously reported. Objective: To carry out in six families from Tolima and Huila departments a descriptive analysis of the presence of the BRCA1 3450del4 mutation associated with breast cancer and familial aggregation. Materials and methods: We conducted a descriptive and cross-sectional study of six index cases with breast cancer positive for BRCA1 3450del4 that fulfilled three of the criteria established by Jalkh, et al. The genealogical trees were made using the information of the interview data (GenoPro™, version 2016). The mutation was typified in healthy and affected relatives who agreed to participate. Results: Thirty of the 78 individuals selected by convenience in the six families presented the mutation BRCA1 3450del4 six of whom developed breast cancer, one, ovarian cancer, one ovarian and breast cancer, and one prostate cancer; 21 did not present any type of neoplasm at the time of the study. Of the 30 individuals carrying the pathogenic variant, six were men, 24 were women, and 13 of these were under 30. Conclusions: In this study of families with the deletion BRCA1 3450del4 in Tolima and Huila we confirmed its association with familial aggregation of breast cancer.

Introducción. El cáncer de mama es un problema mundial de salud pública; entre el 5 y el 10 % de los casos presentan agregación familiar, lo que se explicaría por la presencia de mutaciones en genes de alto riesgo como el BRCA1 y el BRCA2. El origen fundador de la deleción BRCA1 3450del4 en Colombia ya fue reportado. Objetivo. Hacer un análisis descriptivo de seis familias del del Tolima y del Huila con la deleción BRCA1 3450del4 de la asociación de la mutación germinal, con el cáncer de mama y la agregación familiar. Materiales y métodos. Se hizo un estudio descriptivo y transversal de seis casos índice con cáncer de mama positivos para BRCA1 3450del4, que cumplían tres de los criterios establecidos por Jalkh, et al. A partir de la información de las entrevistas, se realizaron los árboles genealógicos (GenoPro™, versión 2016). Se tipificó la mutación en familiares sanos y afectados que aceptaron participar. Resultados. De los 78 individuos seleccionados por conveniencia en las seis familias, 30 presentaron la mutación BRCA1 3450del4; de ellos, seis tenían cáncer de mama, uno, cáncer de ovario, uno, cáncer de mama y ovario, y otro, cáncer de próstata; 21 no presentaban neoplasias. De los 30 individuos portadores de la variante patogénica, seis eran hombres y 24 mujeres, 13 de ellas menores de 30 años. Conclusiones. En este estudio se confirmó la asociación de la deleción BRCA1 3450del4 con el cáncer de mama de agregación familiar.

Cáncer de mama en seis familias del Tolima y el Huila: mutación BRCA1 3450del4 / Breast cancer in six families from Tolima and Huila: BRCA1 3450del4 mutation

Introducción. El cáncer de mama es un problema mundial de salud pública; entre el 5 y el 10 % de los casos presentan agregación familiar, lo que se explicaría por la presencia de mutaciones en genes de alto riesgo como el BRCA1 y el BRCA2. El origen fundador de la deleción BRCA1 3450del4 en Colombia ya fue reportado. Objetivo. Hacer un análisis descriptivo de seis familias del del Tolima y del Huila con la deleción BRCA1 3450del4 de la asociación de la mutación germinal, con el cáncer de mama y la agregación familiar. Materiales y métodos. Se hizo un estudio descriptivo y transversal de seis casos índice con cáncer de mama positivos para BRCA1 3450del4, que cumplían tres de los criterios establecidos por Jalkh, et al. A partir de la información de las entrevistas, se realizaron los árboles genealógicos (GenoPro™, versión 2016). Se tipificó la mutación en familiares sanos y afectados que aceptaron participar. Resultados. De los 78 individuos seleccionados por conveniencia en las seis familias, 30 presentaron la mutación BRCA1 3450del4; de ellos, seis tenían cáncer de mama, uno, cáncer de ovario, uno, cáncer de mama y ovario, y otro, cáncer de próstata; 21 no presentaban neoplasias. De los 30 individuos portadores de la variante patogénica, seis eran hombres y 24 mujeres, 13 de ellas menores de 30 años. Conclusiones. En este estudio se confirmó la asociación de la deleción BRCA1 3450del4 con el cáncer de mama de agregación familiar.

Introduction: Breast cancer is a worldwide public health problem; between 5% and 10% of the cases present familial aggregation explained by genes of high risk such as BRCA1and BRCA2. The founding origin of the deletion BRCA1 3450del4 in Colombia has been previously reported. Objective: To carry out in six families from Tolima and Huila departments a descriptive analysis of the presence of the BRCA1 3450del4 mutation associated with breast cancer and familial aggregation. Materials and methods: We conducted a descriptive and cross-sectional study of six index cases with breast cancer positive for BRCA1 3450del4 that fulfilled three of the criteria established by Jalkh, et al. The genealogical trees were made using the information of the interview data (GenoPro™, version 2016). The mutation was typified in healthy and affected relatives who agreed to participate. Results: Thirty of the 78 individuals selected by convenience in the six families presented the mutation BRCA1 3450del4 six of whom developed breast cancer, one, ovarian cancer, one ovarian and breast cancer, and one prostate cancer; 21 did not present any type of neoplasm at the time of the study. Of the 30 individuals carrying the pathogenic variant, six were men, 24 were women, and 13 of these were under 30. Conclusions: In this study of families with the deletion BRCA1 3450del4 in Tolima and Huila we confirmed its association with familial aggregation of breast cancer.

Tamización para cáncer de mama en el departamento del Huila, Colombia / Screening for mammary cancer in the state of Huila, Colombia

Introducción. En Colombia, la tamización para cáncer de mama, de acuerdo con las normativas del Ministerio de Protección Social, se hace mediante el examen clínico anual de la mama a partir de los 40 años y la mamografía bienal entre los 50 y los 69 años. Se presenta la experiencia en tamización con mamografía y examen clínico de la mama en el departamento del Huila de Colombia. Materiales y métodos. El departamento del Huila, al sur de Colombia, tiene una población de 1'097.615 habitantes, y se seleccionaron 15 municipios para este estudio. La tamización se llevó a cabo entre junio de 2011 y diciembre de 2013, y se adaptó un vehículo que permanecía en cada uno de los municipios durante un tiempo establecido. Dicha unidad móvil contaba con recepción, consultorio médico y unidad de mamografía digitalizada. Se hizo una ronda de tamización con el examen clínico de la mama y la mamografía de dos proyecciones. Resultados. Se valoraron 5.212 mujeres, 4.995 de las cuales contaban con información completa. De estas, 100 (2 %) tenían hallazgos positivos en el examen clínico de la mama. El 51,9 % de las mamografías fueron caracterizadas como BI-RADS 3 y el 1,12 %, como BI-RADS 4 o 5. Se confirmó el diagnóstico de cáncer en 29 pacientes, 9 con carcinoma in situ y 20 con carcinoma infiltrante, de las cuales 17 (59 %) tenían tumores en los estadios clínicos tempranos. Discusión. Se muestra que es posible hacer tamización para cáncer de mama con mamografía y examen clínico de la mama en municipios alejados de los grandes centros urbanos de Colombia, si se cuenta con una infraestructura básica y médicos generales o enfermeras con entrenamiento en la detección temprana del cáncer de mama

Introduction: Breast cancer screening in Colombia is performed following the "Ministerio de Salud y Protección Social" guidelines, through annual clinical examination starting with women 40 years old and biennial mammography in women between 50 and 69 years old. The article shows the experience in screening with mammography and breast clinical examination in the state of Huila, Colombia. Methods and materials: The state of Huila, located in southern Colombia, has a population of 1,097,615. Fifteen townships were selected for the study. Screening was carried out between June 2011 and December 2013. A customized vehicle stayed in every single township during an stablished period of time. This mobile unit was equipped with a reception area, a doctor´s office and a digitalized mammography unit. Screening was performed by breast clinical examination and a two-projection mammography. Results: 5,212 patients were screened, of which 4,995 had complete information. 100 women (2%) had positive clinical breast examination findings; 51.9% of the mammographies were BI-RADS 3, and 56 (1.12%) were BI-RADS 4 or 5. Diagnosis of cancer was confirmed in 29 patients, 9 of them with carcinoma in situ, and 20 with infiltrating carcinoma, of which 17 (59%) had early stage tumors. Discussion: This work shows that it is possible to screen for mammary cancer with mammography and breast clinical examination in townships away from the large urban centers of Colombia, provided there are a basic infrastructure and general physicians or nurses with training in early detection of breast cancer

Frecuencia de cáncer de seno mediante detección temprana en el hospital universitario de Neiva entre el 1 de junio y el 30 de noviembre de 2007 / Incidence of breast cancer by early detection at the University Hospital, Neiva, Colombia, in the period June 1-November 30, 2007

Introducción. El cáncer de seno ha presentado últimamente un aumento significativo en su incidencia, la cual es de 30 por cada 100.000 mujeres en Colombia. La detección temprana, mediante pruebas de tamización, ha generado mayor oportunidad en el manejo y pronóstico de las pacientes. Este estudio busca determinar la frecuencia de cáncer de seno en mujeres que asistieron voluntariamente al programa de detección temprana de cáncer de seno mediante mamografía en el Hospital Universitario de Neiva, entre el 1 de junio y 30 de noviembre de 2007.Materiales y métodos. Se realizó un estudio de corte transversal con pacientes mayores de 40 años, pertenecientes a los niveles 1 y 2 del Sisben (vinculados), que desearan participar en el estudio, en forma voluntaria y gratuita; en este periodo se incluyeron 848 mujeres a quienes se les analizó variables sociodemográficas, clínicas y de diagnóstico propias de la evaluación del cáncer de seno.Resultados y discusión. Del total de la población estudiada, a 18 pacientes (2,1%) se les confirmó el diagnóstico de cáncer de seno en estadio temprano. El más frecuente fue el IIB (44,4%), seguido del estadio IIA (38,9%), a diferencia de los datos suministrados por el Instituto Nacional de Cancerología en 2006, donde la proporción de presentación de cáncer de seno es mayor al momento de la consulta en estadios más avanzados.Por lo anterior, es imperativa la implementación de políticas para la detección temprana y el diagnóstico precoz del cáncer de seno, para mejorar la supervivencia y el pronóstico de las pacientes con este diagnóstico.

Longitud esofágica: correlación con talla y sexo / Esophageal length: a correlation study

Utilizando la endoscopia digestiva alta (EVDA), se realizaron 120 mediciones de longitud esofágica : 60 mujeres y 60 hombres. Se obtuvo un promedio de longitud del esófago de 22 cms para la población general; 21 cms para mujeres y 23 cms para hombres. El presente artículo no logró establecer una correlación estadística entre la longitud esofágica, la talla y el sexo.