Search

Colombia es el segundo país con mayor cantidad de etnias Amerindias del continente gracias a su ubicación geográfica y a que se encuentra en el Noroccidente del continente Sur Americano tuvo que haber sido un corredor para las migraciones de los Amerindios. Pero debido a la mezcla amerindia, europea y africana, ocurrida en diferentes proporciones a lo largo del país hubo cambios en las dinámicas poblacionales. Ojetivo: se caracterizó molecularmente una muestra indígena proveniente de dos etnias – Pijao y Nasa Paez, - y otra muestra de individuos mestizos no relacionados del Tolima; con el fin de identificar heterocigocidad, frecuencias alélicas y distancias Fst, mediante el análisis de 100 marcadores informativos de ancestría (SNPs autosómicos). Metodología: Para la realización de este estudio se obtuvo ADN a partir de muestras de sangre tomadas en personas indígenas y mestizas de las regiones ya mencionadas, para tipificar 100 SNPs autosómicos o Marcadores de informativos de Ancestría (AIMs). Resultados: los análisis de la Heterocigocidad (Het) mostraron que los valores bajos se presentaban en las etnias indígenas Nasa (0,181) y Pijaos (0,250), mientras que los de Planadas (0,402) e Ibagué (0,415) presentaron los valores altos. Los análisis realizados de manera global mostraron que las poblaciones del Tolima son menos heterocigotas que las poblaciones ancestrales. Conclusiones: La población nativa Nasa, es la de mayor conservación de la variación nativa ancestral reflejada con los análisis de heterocigocidad y posee una mayor distancia genética con respecto a las poblaciones mestizas.

Objetivo: Caracterizar las características clínico-patológicas y algunos fenotipos moleculares del cáncer colorrectal (CCR), en 1278 pacientes de la región andina colombiana. Métodos: Se analizó una muestra de 1278 pacientes con CCR. Análisis de expresión de los genes MMR-Mismatch Repair-hMLH1, utilizando métodos inmunohistoquímicos (IHC). Para inestabilidad microsatelital-MSI se utilizó ADN de tejido tumoral-normal mediante PCR. Resultados: Promedio de edad 57,4 años, la enfermedad es más frecuente en el género femenino 53,2%. La frecuencia de pacientes menores de 50 años (26,5%) es mayor a la esperada, el CCR en estos casos se asoció a tipos histológicos agresivos -carcinoma mucinoso y carcinoma en anillo de sello- p=

Resumen 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. Abstract 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.

Context: A recent study reported the nonsynonymous G534E (rs7080536, allele A) variant in the HABP2 gene as causal in familial nonmedullary thyroid cancer (NMTC). Objective: The objective of this study was to evaluate the causality of HABP2 G534E in the TCUKIN study, a multicenter population-based study of NMTC cases from the British Isles. Design and Setting: A case-control analysis of rs7080536 genotypes was performed using 2105 TCUKIN cases and 5172 UK controls. Participants: Cases comprised 2105 NMTC cases. Patient subgroups with papillary (n = 1056), follicular (n = 691), and Hürthle cell (n = 86) thyroid cancer cases were studied separately. Controls comprised 5172 individuals from the 1958 Birth Cohort and the National Blood Donor Service study. The controls had previously been genotyped using genome-wide single nucleotide polymorphism arrays by the Wellcome Trust Case Control Consortium study. Outcome Measures: Association between HABP2 G534E (rs7080536A) and NMTC risk was evaluated using logistic regression. Results: The frequency of the HABP2 G534E was 4.2% in cases and 4.6% in controls. We did not detect an association between this variant and NMTC risk (odds ratio [OR] = 0.896; 95% confidence interval, 0.746–1.071; P = .233). We also failed to detect an association between the HABP2 G534E and cases with papillary (1056 cases; G534E frequency = 3.5%; OR = 0.74; P = .017), follicular (691 cases; G534E frequency = 4.7%; OR = 1.00; P = 1.000), or Hürthle cell (86 cases; G534E frequency = 6.3%; OR = 1.40; P = .279) histology. Conclusions: We found that HABP2 G534E is a low-to-moderate frequency variant in the British Isles and failed to detect an association with NMTC risk, independent of histological type. Hence, our study does not implicate HABP2 G534E or a correlated polymorphism in familial NMTC, and additional data are required before using this variant in NMTC risk assessment.

Resumen:OBJETIVO:Reunir evidencias de la variación en la frecuencia de las mutaciones de BRCA1 y BRCA2 y la historia familiar en pacientes con cáncer de glándula mamaria (CGM) y cáncer de ovario (CO) de diferentes orígenes geográficos.MÉTODO:En este trabajo se realizó una revisión sistemática, siguiendo los parámetros del protocolo PRISMA, para estimar la prevalencia de mutaciones en los genes BRCA 1/2 en pacientes con CGM y CO, la incidencia de la historia familiar y la prevalencia observada en casos esporádicos en este tipo de cáncer.RESULTADOS:Se observa una heterogeneidad en la frecuencia de las mutaciones de estos genes en los estudios de historia familiar, con una variación entre 0.0 y 0.48 en pacientes y familiares con CGM y CO similares a los previamente reportados.DISCUSIÓN: Este amplio rango de la frecuencia se debe al origen de la población estudiada, el número de individuos analizados y la metodología de genotipificación utilizada. La revisión revela que el CGM y CO familiar es dos veces más frecuente, en comparación con los casos de esta misma patología con origen esporádico.CONCLUSIONES:Este tipo de estudios moleculares les permite a las personas que presentan historia familiar con CGM y CO realizarse análisis precoces y chequeos para prevenir en un futuro el desarrollo de alguna de estas neoplasias. Abstract:OBJECTIVE:Collect evidence about the frequency variation of BRCA1 and BRCA2 mutations and family history in patients with mammary gland cancer (MGC) and ovarian cancer (OC) from different geographical backgrounds.METHOD: This paper presents a systematic review using the PRISMA protocol parameters to estimate the prevalence of mutations in BRCA 1/2 genes in patients with MGC and OC, the incidence of family history and the observed prevalence in sporadic cases with this type of cancer.RESULTS:Heterogeneity is observed in the frequency of mutations of these genes in studies of family history ranging between 0.0 and 0.48 in patients and families with MGC and OC similar to those previously reported.DISCUSSION:This wide range of frequency is due to the origin of the studied population, the number of individuals analyzed and genotyping methodology used. The review reveals that the family MGC and OC is twice as common compared with cases of the same disease of a sporadic origin.CONCLUSIONS: This type of molecular studies allows other people who have family history of MGC and OC to perform early analysis and tests to prevent the future development of this neoplasia.

Background: Several colorectal cancer susceptibility disease loci have been discovered through genome-wide association studies. However most of the variants were originally identified in Caucasian populations. Aim: To analyze the role of 20 known risk SNPs for colorectal cancer. Methods: Given that linkage disequilibrium is highly dependent on population demographic history and admixture background, we studied 20 risk SNPs in a pooled sample of 955 cases and 968 controls from admixed populations in Colombia. Results: The replication was reached for 11 out of 20 nominally associated SNPs; with allelic odds ratios (OR) ranging from 1.14 to 1.41, indicating a minimal increase in risk individually, however coinheritance of those SNPs resulted in an overall OR = 5.4 (95% CI: 3.052-9.731, P = 1.16E−08). Most of the variants followed a recessive model consistent with significant homozygous ORs distributed between 1.3 and 1.65. Among the most associated markers we found: rs4939827 (18q21.1, P = 7.35E−6), rs10411210 (19q13.11, P = 0.001), rs10795668 (10p14, P = 0.0024), rs4444235 (14q.2.2, P = 0.005), rs961253 (20p12.3, P = 0.006), rs16892766 (8q23.3, P = 0.011) and rs1050547 (8q24.21, P = 0.017). Conclusion: Our findings in Colombia have addressed the admixture and how this has influenced the risk associated with the known/unknown colorectal cancer regions, providing a comprehensive vision about several CRC-susceptibility SNPs identified in European populations, which also resulted, associated with an increased risk to CRC in the Colombian population, even though frequency and genetic structure differences accounted for those nonreplicated SNPs.

Helicobacter pylori (H. pylori), clasificada como carcinógeno tipo I para cáncer gástrico (CG), ha acompañado al hombre al menos desde hace 116 000 años. Los conocimientos de las fuerzas evolutivas que modulan el rol de esta bacteria en el desarrollo del espectro de enfermedades gástricas son aún escasos. Esta revisión sistemática recopila artículos que reportan un proceso de coevolución, relacionan los componentes ances- trales huésped-hospedero y describen mecanismos adaptativos de H. pylori al entorno gástrico humano, con el fin de comprender si el proceso de coevolución modula la patogenicidad de la bacteria y el desarrollo de enfermedades gástricas. Se realizó una búsqueda sistemática en las bases de datos electrónicas: MEDLINE (OvidSP), Scopus (ScienceDirect), Scielo y Tree of Science (ToS); términos de búsqueda: “stomach”, “can- cer”, “neoplasms”, “ethinicity”, “evolution”, “genetics”, “ancestry” y “Helicobacter pylori”. Idiomas: inglés y es- pañol. Los datos fueron filtrados por un revisor utilizando un formulario estándar de extracción y ulteriormente revisados por otro. El riesgo de sesgo y la calidad metodológica de los estudios fueron evaluadas con el programa: Critical Appraisal Skills Programme (CASP). Del total de 1584 estudios, 36 cumplieron los criterios de inclusión. Los factores más relevantes en el desarrollo del espectro de enfermedades asociadas con la infección por H. pylori son: la disrupción en el proceso de coevolución entre la bacteria y su huésped humano –por la transferencia horizontal de segmentos de genes que no han evolucionado con sus anfitriones–; las sustituciones de aminoácidos; la fijación y la selección positiva principalmente en las regiones hipervariables.

The genetic contributions to breast cancer development among Latinas are not well understood. Here we carry out a genome-wide association study of breast cancer in Latinas and identify a genome-wide significant risk variant, located 5′ of the Estrogen Receptor 1 gene (ESR1; 6q25 region). The minor allele for this variant is strongly protective (rs140068132: odds ratio (OR) 0.60, 95% confidence interval (CI) 0.53–0.67, P=9 × 10−18), originates from Indigenous Americans and is uncorrelated with previously reported risk variants at 6q25. The association is stronger for oestrogen receptor-negative disease (OR 0.34, 95% CI 0.21–0.54) than oestrogen receptor-positive disease (OR 0.63, 95% CI 0.49–0.80; P heterogeneity=0.01) and is also associated with mammographic breast density, a strong risk factor for breast cancer (P=0.001). rs140068132 is located within several transcription factor-binding sites and electrophoretic mobility shift assays with MCF-7 nuclear protein demonstrate differential binding of the G/A alleles at this locus. These results highlight the importance of conducting research in diverse populations., Genome-wide association studies (GWAS) have revealed gene variants associated with breast cancer, but their association with breast cancer development in Latinas is not clear. Here, the authors carry out a GWAS of breast cancer in Latinas and identify a significant protective variant of Indigenous American origin in the 6q25 region.

TC is one of the most common malignancy that shows familial inheritance with ∼8 fold increase in the risk of developing TC in first-degree relatives affected by this disease. Recent genome-wide association studies (GWAS) aimed at characterizing the risk loci for TC have identified five single nucleotide polymorphisms (rs966423, rs2439302, rs965513, rs116909374 and rs944289) associated with increased risk for TC. However, effect of these polymorphisms have bot been studied in any Hispanic population. Therefore, the aim of this study was to analyze the above-mentioned SNPs in 235 TC patients and 588 healthy controls from Central Colombia using KASP genotyping system. Genotype frequencies, Hardy Weinberg equilibrium (HWE) and association testing was carried out using Plink. The cumulative genetic risk was assessed using unweighted and weighted approaches. Significant associations between thyroid cancer risk and rs965513A (OR = 1.503, 95% CI: 1.203-1.886, P = 0.00038) and rs944289T (OR = 1.372, 95% CI: 1.095-1.699, P = 0.00488) was observed in our study. Consistent, yet not -significant associations were observed between disease risk and rs2439302T (OR = 1.177, 95% CI: 0.931-1.477, P = 0.1666) and rs116909374A (OR = 1.626, 95% CI: 0.799-3.766, P = 0.2443). For rs966423G, significant departure from HWE was observed therefore this SNP was excluded from further analysis. The combined analyses of rs2439302, rs965513, rs116909374 and rs944289 showed consistent associations between the number of disease alleles and cancer risk. Having three risk alleles increased disease risk by two-fold (OR = 2.09, 95% CI:1.46 - 3.02),while carrying five risk alleles was associated with nearly 4-fold increase in the disease risk (OR = 3.84, 95% CI:1.47 - 10.06). To our knowledge, this was the first study that assessed TC risk associated with known polymorphisms in the Hispanic population and suggest that these variants could be used in future risk prediction profiling studies in these populations. Citation Format: Ana Estrada-Flórez, Mabel E. Bohórquez-Lozano, Rodrigo Prieto-Sánchez, Gilbert F. Mateus, Alejandro Rios, Alejandro Vélez Hoyos, Carlos S. Duque, Mirko A. Ledda, Maria J. Erazo, Fernando Bolaños, Cesar Panqueba, María Magdalena Echeverry de Polanco, Luis G. Carvajal-Carmona. Evaluation of known low-penetrance thyroid cancer risk alleles in a Hispanic population from South America. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-046. doi:10.1158/1538-7445.AM2015-LB-046

Cancer is a leading cause of non-communicable morbidity and mortality worldwide. Hispanics are the largest and fastest growing ethnic group in the U.S. and the largest population group in the Americas. Due to health care disparities, this population remains understudied and under-screened for cancer causing gene mutations. While many genes that predispose individuals for different cancers have been discovered, the prevalence of mutations in these genes remains largely undetermined in many populations. Developing customized screening panels and screening for novel variants for large population samples can be expensive and time consuming. We have developed a low-cost, high-throughput pipeline and method to screen 480 customizable amplicons (∼20 genes, ∼144Kbp) for up to 384 samples per run. By combining a bioinformatics pipeline for design and analysis with Fluidigm microfluidics PCR and Illumina MiSeq, we can quickly screen multiple cancer panels at a high depth of coverage, at a low cost per sample. The amplicon design pipeline provides ability to develop amplicon primer sets and pooling strategies. Libraries of 384 barcoded samples are run in a single MiSeq lane. Sequencing data is analyzed by an automated pipeline, which aligns using BWA-MEM, calls variants using VarScan 2, and annotates variants using multiple datasets using Annovar. We have applied these pipelines and methods to identify mutation in known cancer genes, such as APC, MSH2, MLH1, BRCA1, and BRCA2, in several hundred Hispanic individuals with familial and early-onset colon and breast cancer. While many of the mutations have been previously reported, we have identified several novel mutations that appear to have Amerindian origin. Moreover, a few are shared among many individuals in isolated geographic locations, suggesting founder effects are common in some of these populations. Over 50% of the patients screened to date have no mutations in our cancer panels; we plan to use these samples to screen for novel genes using whole exome or genome sequencing in the next phase of our study. In conclusion, we have developed a low-cost, high-throughput pipeline for screening customizable panels for known and novel mutations. Our study is an initial step to assess prevalence of known cancer causing genes and identify novel genes/mutations that contribute to different cancers in the Hispanic community. These discoveries provide a foundation for early detection, prevention, and treatment of familial cancers in Hispanic populations. Citation Format: Paul Lott, Ruta Sahasrabudhe, Anna Marie Tuazon, John Williamson, Ana Estrada, Mabel Bohorquez, Rodrigo Prieto, Angel Criollo, Alejandro Velez, Jorge Castro, Gilbert Mateus, María Magdalena Echeverry, Luis Carvajal-Carmona. Development of low-cost high throughput screening pipeline for detecting germline cancer causing mutations in Hispanic populations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1520. doi:10.1158/1538-7445.AM2014-1520