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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. Demographic history and admixture background may impact the association of known CRC variants due to the differences in linkage disequilibrium across different populations. We performed a genomic study in a sample of 955 cases and 968 controls from admixed populations in Colombia by genotyping ∼1 million SNPs aimed to detect the impact of genetic structure in the association of 20 known SNPs risk for colorectal cancer. The replication was reached for eleven out of 20 nominally associated SNPs; with allelic odds ratios (OR) between 1.14 and 1.41, indicating a minimal individual risk increment; on the other hand, the overall OR for co-inherited SNPs was 5.4 (95% CI: 3.052-9.731,P=1.16E-08). Most of the variants followed a recessive model with significant homozygous ORs distributed between 1.3 and 1.65. The major associated markers were: 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). Additionally, European ancestral component was associated with colorectal cancer risk (p=6.48E-04, OR = 4.244 95% IC: 1.701-10.68). Our findings in Colombia indicates a significant contribution of the known CRC risk SNPs to the disease in the Colombian population, which in turns can be explained by the genetic European component influx during the admixture process. The unassociated SNPs indicates frequency and genetic structure differences between European and Colombian populations or due to the sample process.

El Marketing Político diseña y formula estrategias publicitarias con la finalidad de captar el mayor número de votantes posibles. En los últimos años, estas estrategias quieren ser adaptadas a medios de comunicación OTL, que son medios relacionados con el internet y medios digitales. El objetivo de investigación es analizar la efectividad los componentes de los medios de comunicación OTL y como estos tienen incidencia en la captación de votantes. Se consideró a los votantes oficiales registrados en las últimas elecciones seccionales 2.019. El abordaje de los métodos se sustentó en un tipo exploratorio, con modalidad bibliográfica y un enfoque cuantitativo, mediante la aplicación de una encuesta. Los resultados aportan un análisis de los componentes de los medios OTL, como herramientas más utilizadas, tipos de estrategias, temas de interés y percepción de anuncios. Se concluye una buena aceptación de las características y bondades de los medios de comunicación OTL, pero no por encima de los medios de comunicación tradicionales.

Helicobacter pylori have coevolved with mankind since its origins, adapting to different human groups. In America H. pylori has evolved in several subpopulations specific for regions or even countries. In this study we analyzed the genome of 163 Colombian strains along with 1,113 strains that represent worldwide H. pylori populations to better discern the ancestry and adaption to Colombian people. Population structure was inferred with FineStructure and chromosome painting identifying the proportion of ancestries in Colombian isolates. Phylogenetic relationship was analyzed using the SNPs present in the core genome. Also, a Fst analysis was done to identify the gene variants with the strongest fixation in the identified Colombian subpopulations in relation to their parent population hspSWEurope. Worldwide, population structure analysis allowed the identification of two Colombian subpopulations, the previously described hspSWEuropeColombia and a novel subpopulation named hspColombia. In addition, three subgroups of H. pylori were identified within hspColombia that follow their geographic origin. The Colombian H. pylori subpopulations represent an admixture of European, African and Native indigenous ancestry; although some genomes showed a high proportion of self-identity, suggesting a strong adaption to these mestizo Colombian groups. The Fst analysis identified 82 SNPs significantly fixed in 26 genes of the hspColombia subpopulation that encode mainly for outer membrane proteins and proteins involved in central metabolism. The strongest fixation indices were identified in genes encoding the membrane proteins HofC, HopE, FrpB-4 and Sialidase A. These findings demonstrate that H. pylori has evolved in Colombia to give rise to subpopulations following a geographical structure, evolving to an autochthonous genetic pool, drive by a positive selective pressure especially on genes encoding for outer membrane proteins.

Introducción. El cáncer colorrectal es una carga para la salud pública en Colombia y el mundo. Estudios de asociación genética han identificado regiones cromosómicas asociadas a esta enfermedad, mostrando riesgo variable entre poblaciones, debido a la historia demográfica y la ancestría genética. Objetivo. Estudiar el riesgo que aportan 20 marcadores al cáncer colorrectal en Colombia, empleando 955 casos y 972 controles del consorcio CHIBCHA, analizando conjuntamente el efecto de la ancestría genética global y local. Metodología. Las muestras se genotipificaron usando microarreglos Axyom Affymetrix LAT y CUSTOME, para obtener los genotipos genómicos globales, incluyendo 20 SNPs de riesgo. Los análisis estadísticos se realizaron en PLINK (asociaciones), ADMIXTURE (ancestría global), Elai (ancestría local) y R (modelos logísticos). Resultados. Once regiones cromosómicas resultaron asociadas presentando ORs entre 1.14 y 1.41 (p

The G allele of the rs6983267 single-nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer (TC) has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in TC susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3067 cases and 8575 controls. We detected significant associations between rs6983267G and TC in the British Isles (odds ratio (OR)=1.19, 95% CI: 1.11–1.27, P=4.03×10−7), Japan (OR=1.20, 95% CI: 1.03–1.41, P=0.022) and a borderline significant association of similar effect direction and size in Colombia (OR=1.19, 95% CI: 0.99–1.44, P=0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5484 cases and 12 594 controls, confirmed the association between rs6983267G and TC (P=1.23×10−7, OR=1.13, 95% CI: 1.08–1.18). Our results therefore support the notion that rs6983267G is a bona fide TC risk variant that increases the risk of disease by ∼13%.

Copyright © 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved. Colorectal cancer (CRC) is a major public health problem, and its incidence is rising in developing countries. However, studies characterizing CRC clinicopathological features in cases from developing countries are still lacking. The goal of this study was to evaluate clinicopathological and demographic features in one of the largest CRC studies in Latin America. The study involved over 1525 CRC cases recruited in a multicenter study in Colombia between 2005 and 2014 as part of ongoing genetic and epidemiological studies. We gathered clinicopathological data such as age at diagnosis, sex, body mass index, tobacco and alcohol consumption, family history of cancer, and tumor features including location, histological type, and stage. Statistical analyses were performed to test the association between age of onset, sex, and clinical manifestations. The average age at CRC diagnosis was 57.4 years, with 26.5% of cases having early-onset CRC (diagnosed by age 50 years). Most cases were women (53.2%; P=0.009), 49.2% were overweight or obese, 49.1% were regular alcohol drinkers, 52% were smokers/former smokers, and 12.2% reported relatives with cancer. Most tumors in the study were located in the rectum (42.7%), were adenocarcinomas (91.5%), and had advanced stage (T3-T4, 79.8%). Comparisons by sex found that male cases were more likely to be obese (36.5% vs 31.1%; P=0.001), less likely to have a family history of cancer (9.7% vs 15.3%; P=0.016), and more likely to have advanced-stage tumors (83.9% vs 76.1%; P=0.036). Comparisons by age of onset found that early-onset cases were more likely to be women (59.3% vs 51.0%; P=0.005) and report a family history of cancer (17.4% vs 10.2%; P=0.001). To our knowledge, our study is the largest report of clinicopathological characterization of Hispanic CRC cases, and we suggest that further studies are needed to understand CRC etiology in diverse Hispanic populations.

Breast cancer (BC) is the most commonly diagnosed cancer among women, with 1 in every 7 women in the U.S. developing BC in their lifetime. While BC may not be the leading cause of cancer incidence in many minority populations, such as Hispanics, it is the leading cause of cancer death, highlighting a cancer disparity. Moreover, the contribution of mutations in BC susceptibility genes remains poorly investigated in Hispanic populations. To begin to address these voids, we screened Colombian BC patients for common BRCA1 and BRCA2 mutations using the KASP genotyping system. Strikingly, 27 of 722 unselected cases (4%) harbored the same BRCA1 3450del4 mutation. Clinical data and family history indicate that these individuals originate from a distinct geographic region in Colombia, Neiva. Significantly, 10% of the unselected BC cases in Neiva and the surrounding region harbor the 3450del4 mutation, potentially representing one of the most profound founder effects reported in human populations. Interesting, this BRCA1 mutation has also been reported in other countries, including Portugal, Spain, and Chile. To determine whether this mutation stems from a single origin, mutation carriers from each of these countries (n = 26), along with mutation carriers from Colombia (n = 27), were subjected to the Affymetrix Axiom Human UK Biobank Array (>800 thousand markers). Haplotypes in which the BRCA1 mutation resides were estimated by SHAPEIT, and pairwise segmental sharing was determined using GERMLINE. Our data suggest that the mutation carriers, although from different countries and continents, share a core haplotype, likely to have originated from Spain. Additionally, the mutation seems to be fairly new to Colombia, with individuals sharing up to a 40Mb haplotype comprising the mutation. We are currently estimating the age of the mutation using the bioinformatic software DMLE+, which exploits the rate of linkage disequilibrium decay due to recombination. By understanding the prevalence of mutations in known breast cancer risk genes in minority populations, cancer disparities can be better addressed and breast cancer screening can be improved. Furthermore, these findings have direct implications in robust and cost-effective targeted screening in regions where there is a high prevalence of the BRCA1 3450del4 mutation. Citation Format: Anna Marie De Asis Tuazon, Carolina Ramirez, Mabel Bohorquez, Rodrigo Prieto, Paul Lott, Angel Criollo, Ana Estrada, Gillbert Mateus, Alejandro Velez, Justo Ramirez, COLUMBUS Consortium, Manuel Teixeira, Ana Vega, Conxi Lazaro, Eva Tornero, Cristina Martinez, Mar Infante, Miguel De La Hoya, Orland Diez, Pilar Carvallo, Magdalena Echeverry, Luis Carvajal-Carmona. Transcontinental characterization of the Hispanic BRCA1 3450del4 breast cancer founder mutation. [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 2739. doi:10.1158/1538-7445.AM2015-2739

Cancer is a leading cause of non-communicable morbidity and mortality worldwide. While many genes that predispose individuals for different cancers have been discovered, the population prevalence of mutations in these genes remains largely undetermined in many populations. Developing customized screening panels and screening for novel variants for a 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 the full coding sequence of multiple cancer panels at a high depth of coverage at a low cost per sample (∼$20-40/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 these mutations have been previously reported, we have identified several novel pathogenic changes that appear to have Amerindian origin. Of which, a few are shared among many individuals in isolated geographic locations, suggesting founder effects are common in some of these populations. In conclusion, we have developed a low-cost high-throughput method for screening customizable panels for known and novel mutations. These panels typically consist of 20 cancer genes and our group has already developed panels that are specific for breast cancer, colon cancer and thyroid cancer. 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. Citation Format: Ruta Sahasrabudhe,, Paul Lott, Anna Marie Tuazon, John Williamson, Natalia Belter, Ana Estrada, Mabel Bohorquez, Rodrigo Prieto, Angel Criollo, Alejandro Velez, Jorge Castro, Gilbert Mateus, Magdalena Echhevery, Luis G. Carvajal-Carmona. Development of low-cost high-throughput screening methods for detecting germline mutations in multiple cancer genes. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr 42. doi:10.1158/1538-7445.CANSUSC14-42

Colorectal and breast cancers are leading causes of cancer morbidity and mortality in Hispanics. Most of the genes predisposing to these common malignancies are yet to be identified. Moreover, the prevalence of mutations in known cancer genes in Hispanic populations remains largely undetermined. Our present study aims to establish the prevalence of mutations that predispose to cancer susceptibility syndromes in Hispanics using a high throughput next-generation sequencing approach. We have developed an amplicon sequencing method that uses microfluidics PCR to simultaneously identify mutations in up to 480 amplicons. This amount of sequence data is enough to cover, at a high depth, the coding sequence of ∼20 different genes in a single reaction. To do so, the samples are barcoded individually using indexing adapters that allows pooling of multiple amplicon libraries for up to 384 samples in a single MiSeq run. The sequence data is analyzed with a locally developed bioinformatics pipeline that uses BWA, VarScan V2.0 and custom shell and Perl scripts. Our preliminary data, in several hundred familial and early-onset colon and breast cancer patients from South America, have identified many individuals with mutations in known cancer genes, such as APC, MSH2, MLH1, BRCA1 and BRCA2, and that have been previously reported in Southern European populations. We have also identified several mutations that have not been reported previously and that appear to have an Amerindian origin. Interestingly, a large fraction of these mutations are shared by multiple patients and suggest that founder effects are common in some of these populations. We have also found that more than over 50% of the patients screened so far are mutation negative. We plan to use this latter set of samples for novel gene discovery by whole exome or genome sequencing in the next phase of our study. In conclusion, we have developed a rapid, cost effective, and efficient method for screening mutations in known cancer genes in the Hispanic population. Hispanics are the youngest, largest and the fastest growing US minority and the largest population group living in the Americas. However, to a large extent, this population remains under-studied and under-screened, contributing to health care disparities. Prevalence of mutations in known cancer genes as well as novel mutations identified in our study can be used during initial steps of genetic testing programs that can improve the detection of early cancers among Hispanic communities. Citation Format: Ruta Sahasrabudhe, Anna-Marie Tuazon, Paul Lott, Ana Estrada, Mabel Bohorquez, Rodrigo Prieto, Angel Criollo, Carolina Ramirez, Magdalena Echeverry, Luis G. Carvajal-Carmona. Development of high-throughput screening methods for detecting germline cancer causing mutations in the Hispanic population. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B10. doi:10.1158/1538-7755.DISP13-B10

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