Avaliação da saúde sexual nas pacientes sobreviventes ao câncer de mama e do grau de interesse em resolver as dificuldades na consulta médica

Natalia Camejo: Asistente del Servicio de Oncología. Hospital de Clínicas “Dr. Manuel Quintela”. Facultad de Medicina. Universidad de la República, Uruguay. ORCID: 0000-0002-8684-0291 -- Cecilia Castillo: Prof. Adj. del Servicio de Oncología. Hospital de Clínicas “Dr. Manuel Quintela”. Facultad de Medicina. Universidad de la República, Uruguay. ORCID: 0000-0002-0417-0512.-- Ana Laura Hernández: Prof. Adj. del Departamento de Psicologia Medica, Hospital de Clínicas, “Dr. Manuel Quintela”. Facultad de Medicina. Universidad de la República, Uruguay. ORCID: 0000-0001-7335-9530.-- Nora Artagaveytia: Prof. Adj. del Departamento Básico de Medicina, Hospital de Clínicas, “Dr. Manuel Quintela”. Facultad de Medicina. Universidad de la República, Uruguay. ORCID: 0000-0001-8798-7941.-- Dahiana Amarillo: Asistente del Servicio de Oncología. Hospital de Clínicas “Dr. Manuel Quintela”. Facultad de Medicina. Universidad de la República, Uruguay. ORCID: 0000-0002-8615-8639.-- Lucia Delgado: Prof. Directora del Servicio de Oncología. Hospital de Clínicas. Servicio de Oncología Hospital de Clínicas “Dr. Manuel Quintela”. Facultad de Medicina. Universidad de la República, Uruguay. ORCID: 0000-0002-2966-5490. Contacto: [email protected]ón: Las disfunciones sexuales producidas por el cáncer de mama y sus diversas formas de tratamiento se encuentran presentes hasta en el 60 % de las pacientes. En la actualidad la sexualidad sigue siendo un tema eludido, a menudo los médicos omiten tratarlo aduciendo falta de tiempo, conocimiento y experiencia para abordarlo. Objetivos: Evaluar la sexualidad de las pacientes sobrevivientes de cáncer de mama, indagar sobre el grado de interés en recibir ayuda para resolver las disfunciones sexuales vinculas al diagnóstico y al tratamiento de la enfermedad y el nivel de satisfacción con la atención recibida. Materiales y métodos: Se incluyeron pacientes diagnosticadas de cáncer de mama precoz asistidas en la Unidad de Mastología del Servicio de Oncología del Hospital de Clínicas. Se contó con la aprobación del Comité de Ética del Hospital de Clínicas. El cuestionario seleccionado es el utilizado en la Clínica de Oncología Médica de la Universidad de Chicago. Se incluyeron 128 pacientes, la mayoría eran mayores de 50 años y tenían pareja, 98 pacientes (76,5 %) estuvieron sexualmente activas en los últimos 12 meses y 85 (86,7 %) tuvieron problemas sexuales. Resultados: La mayoría (67 pacientes, 68,3 %) respondió que la sexualidad era importante en su vida, 85 (86,6 %) se mostró interesada en recibir atención para tratar sus problemas sexuales y 72 (73,4 %) considera probable abordar los mismas con un médico. Sin embargo, tan sólo 29 (29,6 %) había solicitado ayuda médica para tratarlos, y la mayoría quedó insatisfecha con la atención recibida. El 80,6 % (79) estaría dispuesta a participar de un programa dirigido a confrontar los problemas sexuales. Conclusiones: Nuestros resultados revelan la necesidad de atención de los problemas sexuales de las pacientes diagnosticadas y tratadas por cáncer de mama. Los futuros estudios deberán enfocarse en desarrollar y evaluar el éxito de las intervenciones específicas en el tratamiento de la disfunción sexual en estas pacientes y, lo que es más importante aún, diseñar estrategias para su prevención.Introduction: Sexual dysfunction from breast cancer and its various therapies is present in up to 60 % of the breast cancer patients. Sexuality remains a neglected issue; doctors often ignore it, claiming they lack the time, knowledge or expertise required to address it. Objectives: To evaluate the sexuality of breast cancer survivors’, inquire about the degree of interest in receiving help to resolve sexual dysfunctions related to the diagnosis and treatment of the disease and the level of satisfaction with the care received. Materials and methods: The subjects enrolled had an early breast cancer and were treated at the Mastology Unit of the Cancer Department of the Hospital de Clínicas. The study was approved by the hospital’s Ethics Committee. The selected questionnaire is the one used at the University of Chicago Medical Oncology Clinic. Most of the 128 patients included were over 50 years old and had a sexual partner, 98 patients (76.5 %) had been sexually active within the last 12 months and 85 (86.7 %) reported having sexual problems. Results: Most patients (67/128, 68.3 %) responded that sexuality was important in their lives; 85 (86.6 %) were interested in receiving support to treat their sexual difficulties, and 72 (73.4 %) saw the feasibility of addressing them with a doctor. However, only 29 (29.6%) had sought medical help for that purpose, and most were unhappy with the care received. Seventy-nine patients (80.6 %) would be willing to participate in a program aimed at confronting their sexual problems. Conclusions: Our results reveal the need to address the sexual problems of patients diagnosed with and treated for breast cancer as part of their medical care. Future studies should focus on developing and evaluating the success of specific interventions in the management of these patients’ sexual dysfunction and ―even more importantly― designing strategies for its prevention.Atualmente, a sexualidade continua sendo uma questão evitada, e muitas vezes os médicos não abordam o assunto alegando falta de tempo, conhecimento e experiência para tratá-lo. Objetivos: Avaliar a saúde sexual das pacientes sobreviventes ao CM e o grau de interesse em receber ajuda médica para abordar e tratar seus problemas sexuais. Material e métodos: Foram incluídas pacientes diagnosticadas com CM precoce, atendidas na Unidade de Mastologia do Serviço de Oncologia do Hospital de Clínicas, O questionário selecionado é o utilizado na Clínica de Oncologia Médica da Universidade de Chicago. Resultados: Foram incluídas 128 pacientes, a maioria tinha parceiro e idade acima de 50 anos, 98 pacientes (76,5 %) se mantiveram sexualmente ativas nos últimos 12 meses e 85 (86,7 %) tiveram problemas sexuais. A maioria (67 pacientes; 68,3 %) respondeu que a sexualidade era importante na sua vida, 85 (86,6 %) mostraram interesse em receber atendimento para tratar suas dificuldades sexuais, e 72 (73,4 %) consideraram provável falar sobre essas dificuldades com um médico. No entanto, apenas 29 (29,6 %) tinham procurado ajuda médica para tratá-las, e a maioria delas ficaram insatisfeitas com o atendimento recebido. 80,6 % (79) estariam dispostas a participar de um programa voltado a confrontar os problemas sexuais. Conclusões: Nossos resultados revelam a necessidade de atendimento médico na saúde sexual das pacientes diagnosticadas e tratadas por CM. Os futuros estudos deverão estar focados em desenvolver e avaliar o sucesso das intervenções específicas no tratamento da disfunção sexual nessas pacientes e, o que é ainda mais importante, em desenhar estratégias para sua prevenção

Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients

Background: the study of genetic variants alone is not enough to explain a complex disease like cancer. Alterations in DNA methylation patterns have been associated with different types of tumor. In order to detect markers of susceptibility for the development of cutaneous melanoma and breast cancer in the Uruguayan population, we integrated genetic and epigenetic information of patients and controls. Methods: we performed two case-control studies that included 49 individuals with sporadic cutaneous melanoma and 73 unaffected controls, and 179 women with sporadic breast cancer and 209 women controls. We determined the level of global leukocyte DNA methylation using relative quantification of 5mdC by HPLC, and we compared methylation levels between cases and controls with nonparametric statistical tests. Since the Uruguayan population is admixed and both melanoma and breast cancer have very high incidences in Uruguay compared to other populations, we examined whether individual ancestry influences global leucocyte DNA methylation status. We carried out a correlation analysis between the percentage of African, European and Native American individual ancestries, determined using 59 ancestry informative markers, and global DNA methylation in all participants. Results: we detected global DNA hypomethylation in leukocytes of melanoma and breast cancer patients compared with healthy controls (p < 0.001). Additionally, we found a negative correlation between African ancestry and global DNA methylation in cancer patients (p <0.005). Conclusions: these results support the potential use of global DNA methylation as a biomarker for cancer risk. In addition, our findings suggest that the ancestral genome structure generated by the admixture process influences DNA methylation patterns, and underscore the importance of considering genetic ancestry as a modifying factor in epigenetic association studies in admixed populations such as Latino ones

Surveys on prevention of breast cancer in a population of uruguayan women

Natalia Camejo Martínez: Asistente del Servicio de Oncología Clínica, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Uruguay.-- Cecilia Castillo: Prof. Adj. del Servicio de Oncología Clínica, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Uruguay.-- Nora Artagaveytia: Prof. Adj. del Departamento Básico de Medicina, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Uruguay.-- Ana Laura Hernández: Prof. Adj. del Departamento de Psicología Medica, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Uruguay.-- Andrea Schiavone: Asistente del Servicio de Oncología Clínica, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Uruguay.-- Soledad Milans: Prof. Adj. con Orientación en Imagenología Mamaria del Departamento de Imagenología, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Uruguay.-- Guillermo Laviña: Ex Prof. Adj. Clínica Quirúrgica 1, Facultad de Medicina, Universidad de la República, Uruguay.-- Lucía Delgado: Prof. Directora del Servicio de Oncología Clínica, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Uruguay.-- Contacto: [email protected] cáncer de mama ocupa el primer lugar en incidencia y mortalidad en el Uruguay. El conocimiento de la distribución de los factores de riesgo relacionados con el desarrollo de la enfermedad facilita la incorporación de estrategias de prevención en la práctica clínica habitual, lo que podría contribuir a disminuir los índices de morbimortalidad. Objetivos: conocer el perfil epidemiológico para el cáncer de mama y la frecuencia del control mamográfico en la población encuestada. Material y Métodos: Se aplicó una encuesta a mujeres uruguayas, luego de realizada, se les brindó información sobre los factores de riesgo y protectores y sobre la importancia de realizar el control mamográfico. Resultados: Se incluyeron 182 encuestadas, la mediana de edad fue 34 años (18-75 años). Excluyendo el sexo femenino (factor de riesgo presente en todas las encuestadas), 73 encuestadas (48%) presentaban uno o más factores de riego. La mayoría de las mujeres mayores de 50 años (58; 87,8%), realizaban control mamográfico al menos en forma bianual. Conclusiones: Concordantemente con lo reportado por el Programa Nacional de Cáncer de Mama, 40% de las encuestadas tuvieron algún factor de riesgo. La mayoría de las encuestadas mayores de 50 años realizaban control mamográfico y clínico al menos en forma bianual. Si bien, debido a las características del trabajo, solamente podemos obtener conclusiones sobre las mujeres incluidas, los datos recogidos nos permiten conocer mejor el perfil epidemiológico de la población uruguaya, lo que puede contribuir a las prácticas de prevención.Breast cancer ranks fi rst in incidence and mortality in Uruguay. The knowledge of the distribution of risk factors related to the development of the disease facilitates the incorporation of prevention strategies in routine clinical practice, which could contribute to lower morbidity and mortality rates. Objectives: to know the epidemiological profi le for breast cancer and the frequency of mam mographic control in the surveyed population. Material and Methods: A survey was applied to Uruguayan women. After the same, they were given information about the risk and protective factors and the importance of performing mammographic control. Results: 182 respondents were included; the median age was 34 years (18-75 years). Excluding the female sex (risk factor present in all respondents), 73 respondents (48%) had one or more risk factors. The majority of women older than 50 years (58; 87.8%), performed mammographic control at least biannually. Conclusions: Consistent with what was reported by the National Breast Cancer Program, 40% of the respondents had some risk factor. The majority of respondents over 50 years of age performed mammographic and clinical control at least bi-annually. Although, due to the characteristics of the work, we can only draw conclusions about the women included, the data collected allow us to better understand the epidemiological profi le of the Uruguayan population, which can contribute to prevention practices.O câncer de mama ocupa o primeiro lugar em incidência e mortalidade no Uruguai. O conhecimento da distribuição dos fatores de risco relacionados ao desenvolvimento da doença facilita a incorporação de estratégias de prevenção na prática clínica de rotina, o que poderia contribuir para menores taxas de morbidade e mortalidade. Objetivos: Conhecer o perfi l epidemiológico do câncer de mama e frequência de controle da população mamográfi ca encuestada. Material e Métodos: A pesquisa foi aplicada mulheres uruguaias. Após o mesmo, foram dadas in formações sobre os fatores de risco e proteção e a importância da realização do controle mamográfico. Resultados: 182 respondentes foram incluídos, a mediana de idade foi de 34 anos (18-75 anos). Excluindo o sexo feminino (fator de risco presente em todos os entrevistados), 73 entrevistados (48%) apresentavam um ou mais fatores de risco. A maioria das mulheres com idade superior a 50 anos (58; 87,8%) realizaram o controle mamográfico pelo menos semestralmente. Conclusões: Consistente com o que foi relatado pelo National Breast Cancer Program, 40% dos respondentes tinham algum fator de risco. A maioria dos entrevistados com mais de 50 anos de idade realizou controle mamográfi co e clínico pelo menos bianualmente. Embora, devido às características do trabalho, só podemos tirar conclusões sobre mulheres incluídas, os dados coletados nos permitem compreender melhor o perfi l epidemiológico da população uruguaia, que pode contribuir para práticas de prevenção

Genetic ancestry and social stratification in Montevideo, Uruguay

Diversos estudios genéticos han demostrado que la población uruguaya es trihíbrida, formada por europeo/mediterráneos, indígenas y africanos, cuyo aporte varía en distintas regiones del país. Pese a que Montevideo es la capital de la República, hay escasos estudios sobre los orígenes de su población, que pueden diferir de otras regiones. En este trabajo se propone indagar sobre estos orígenes a partir de información genética en una muestra derivada de una previamente publicada, profundizando en algunas características para determinar su posible influencia en la estimación de la ancestría. Se consideró una muestra de 269 mujeres (casos y controles de un estudio de cáncer de mama) en quienes se analizaron haplogrupos y secuencias de las regiones hipervariables del ADN mitocondrial (ADNmt) y marcadores individuales de ancestría (AIMs) del ADN nuclear. Se observó que había diferencias en los porcentajes de ancestría cuando se analizaban separadamente las personas que se atendían en el sistema público de salud en relación a las que lo hacían en el sistema mutual, con diferencias significativas para el aporte indígena y el europeo/mediterráneo. Luego de corregidos los valores por lugar de atención de salud, se estimaron los siguientes aportes: 24.6% indígena, 67,7% europeo/mediterráneo y 7,7% africano para herencia materna, y de 11,1% indígena, 81,4% europeo/mediterráneo, y 7,5% africano para la herencia biparental. Se analizaron particularmente los aportes indígena y africano y se discutieron los resultados con relación a otros estudios. Debido a las diferencias encontradas relacionadas con la heterogeneidad de la población montevideana, se alerta sobre el muestreo y valores de referencia para estudios poblacionales futuros.Asociación de Antropología Biológica de la República Argentin

Ancestría genética y estratificación social en Montevideo, Uruguay

Several genetic studies have demonstrated that Uruguayan peoples are a trihybrid population, deriving from European/Mediterranean, Native American, and African ancestries that vary by region within the country. Studies on ancestries and origins that focus on Montevideo, the capital of Uruguay, are scarce and may differ from a general country-wide sample. We investigated the genetic origin of the population of Montevideo using a sample derived from a previously published study, in which we examined different factors that could influence ancestry estimations. The sample consisted of 269 women (cases and controls from a breast cancer research study). Haplogroups and hypervariable regions of the mitochondrial DNA, as well as nuclear ancestry informative markers, were analyzed. Differences in ancestral contributions were found when analyzing women attending public hospitals compared to those attending private clinics, with significant differences between Native American and European/Mediterranean contributions. After adjusting for health care system, we estimated the following contributions for the overall population of Montevideo: 24.6 % Native American, 67.7 % European, and 7.7 % African for maternal inheritance, and 11.1 % Native American, 81.4 % European, and 7.5 % African for biparental inheritance. We focused in particular on Native American and African contributions, and the results were discussed considering other sources of evidence. Due to the differences found between subsamples, caution is advised about sampling strategies and reference values to be used in further population studies.Diversos estudios genéticos han demostrado que la población uruguaya es trihíbrida, formada por europeo/mediterráneos, indígenas y africanos, cuyo aporte varía en distintas regiones del país. Pese a que Montevideo es la capital de la República, hay escasos estudios sobre los orígenes de su población, que pueden diferir de otras regiones. En este trabajo se propone indagar sobre estos orígenes a partir de información genética en una muestra derivada de una previamente publicada, profundizando en algunas características para determinar su posible influencia en la estimación de la ancestría. Se consideró una muestra de 269 mujeres (casos y controles de un estudio de cáncer de mama) en quienes se analizaron haplogrupos y secuencias de las regiones hipervariables del ADN mitocondrial (ADNmt) y marcadores individuales de ancestría (AIMs) del ADN nuclear. Se observó que había diferencias en los porcentajesde ancestría cuando se analizaban separadamente las personas que se atendían en el sistema público de salud en relación a las que lo hacían en el sistema mutual, con diferencias significativas para el aporte indígena y el europeo/mediterráneo. Luego de corregidos los valores por lugar de atención de salud, se estimaron los siguientes aportes: 24.6% indígena, 67,7% europeo/mediterráneo y 7,7% africano para herencia materna, y de 11,1% indígena, 81,4% europeo/mediterráneo, y 7,5% africano para la herencia biparental. Se analizaron particularmente los aportes indígena y africano y se discutieron los resultados con relación a otros estudios. Debido a las diferencias encontradas relacionadas con la heterogeneidad de la población montevideana, se alerta sobre el muestreo y valores de referencia para estudios poblacionales futuros

Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60- month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸ 1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher’s exact tests and the OS by Kaplan–Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.Fil: de Almeida, Liz María. Instituto Nacional de Câncer; BrasilFil: Cortés, Sandra. Pontificia Universidad Católica de Chile; ChileFil: Vilensky, Marta. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Valenzuela, Olivia. Universidad de Sonora; MéxicoFil: Cortes Sanabria, Laura. Hospital de Especialidades Centro Medico Nacional Siglo XXI; MéxicoFil: de Souza, Mirian. Instituto Nacional de Câncer; BrasilFil: Barbeito, Rafael Alonso. Universidad de la República; UruguayFil: Abdelhay, Eliana. Instituto Nacional de Câncer; BrasilFil: Artagaveytia, Nora. Universidad de la Republica; UruguayFil: Daneri Navarro, Adrian. Universidad de Guadalajara; MéxicoFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Müller, Bettina. Instituto Nacional del Cáncer; ChileFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Velazquez, Carlos. Universidad de Sonora; MéxicoFil: Alcoba, Elsa. Hospital Maria Curie; ArgentinaFil: Alonso, Isabel. Centro Hospitalario Pereira Rossell; UruguayFil: Bravo, Alicia I.. Hospital Higa Eva Perón; ArgentinaFil: Camejo, Natalia. Universidad de la República; UruguayFil: Carraro, Dirce Maria. A. C. Camargo Cancer Center; BrasilFil: Castro, Mónica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Cataldi, Sandra. Instituto Nacional del Cáncer; UruguayFil: Cayota, Alfonso. Instituto Pasteur de Montevideo; UruguayFil: Cerda, Mauricio. Universidad de Chile; ChileFil: Colombo, Alicia. Universidad de Chile; ChileFil: Crocamo, Susanne. Instituto Nacional de Câncer; BrasilFil: Silva-Garcia, Aida A.. Universidad de Guadalajara; MéxicoFil: Viña, Stella. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Zagame, Livia. Instituto Jalisciense de Cancerología; MéxicoFil: Jones, Beth. University of Yale; Estados UnidosFil: Szklo, Moysés. University Johns Hopkins; Estados Unido

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients

Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857).Fil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Abdelhay, Eliana Saul Furquim Werneck. Instituto Nacional de Cancer; BrasilFil: Artagaveytia, Nora. Universidad de la Republica; UruguayFil: Daneri Navarro, Adrián. Universidad de Guadalajara; MéxicoFil: Müller, Bettina. Instituto Nacional del Cáncer; ChileFil: Velazquez, Carlos. Universidad de Sonora; MéxicoFil: Alcoba, Elsa B.. Hospital Maria Curie; ArgentinaFil: Alonso, Isabel. Centro Hospitalario Pereira Rossell; UruguayFil: Alves Da Quinta, Daniela Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Argentina de la Empresa; ArgentinaFil: Binato, Renata. Instituto Nacional de Cancer; BrasilFil: Bravo, Alicia Inés. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Camejo, Natalia. Universidad de la Republica; UruguayFil: Carraro, Dirce Maria. Centro Internacional de Pesquisa; BrasilFil: Castro, Mónica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Castro Cervantes, Juan M.. Umae Hospital de Especialidades Centro Medico Nacional Siglo XXI; MéxicoFil: Cataldi, Sandra. Instituto Nacional del Cáncer; UruguayFil: Cayota, Alfonso. Instituto Pasteur de Montevideo; UruguayFil: Cerda, Mauricio. Universidad de Chile; ChileFil: Colombo, Alicia. Universidad de Chile; ChileFil: Crocamo, Susanne. National Cancer Institute; Estados UnidosFil: Del Toro Arreola, Alicia. Universidad de Guadalajara; MéxicoFil: Delgadillo Cisterna, Raúl. Umae Hospital de Especialidades Centro Medico Nacional Siglo Xxi; MéxicoFil: Delgado, Lucía. Universidad de la Republica; UruguayFil: Fernandez, Elmer Andres. Area de Cs. Agrarias, Ingeniería, Cs. Biológicas y de la Salud de la Universidad Catollica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Fejerman, Laura. University of California at Davis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Trinchero, Alejandra. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Valenzuela, Olivia. Universidad de Sonora; MéxicoFil: Vedham, Vidya. National Cancer Institute; Estados UnidosFil: Zagame, Livia. Instituto Jalisciense de Cancerología; MéxicoFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Genomic Diversity in Sporadic Breast Cancer in a Latin American Population

Among Latin American women, breast cancer incidences vary across populations. Uruguay and Argentina have the highest rates in South America, which are mainly attributed to strong, genetic European contributions. Most genetic variants associated with breast cancer were described in European populations. However, the vast majority of genetic contributors to breast cancer risk remain unknown. Here, we report the results of a candidate gene association study of sporadic breast cancer in 176 cases and 183 controls in the Uruguayan population. We analyzed 141 variants from 98 loci that have been associated with overall breast cancer risk in European populations. We found weak evidence for the association of risk variants rs294174 (ESR1), rs16886165 (MAP3K1), rs2214681 (CNTNAP2), rs4237855 (VDR), rs9594579 (RANKL), rs8183919 (PTGIS), rs2981582 (FGFR2), and rs1799950 (BRCA1) with sporadic breast cancer. These results provide useful insight into the genetic susceptibility to sporadic breast cancer in the Uruguayan population and support the use of genetic risk scores for individualized screening and prevention

Translational machinery and protein folding: Evidence of conformational variants of the estrogen receptor alpha

As an approach to understand how translation may affect protein folding, we analyzed structural and functional properties of the human estrogen receptor alpha synthesized by different eukaryotic translation systems. A minimum of three conformations of the receptor were detected using limited proteolysis and a sterol ligand-binding assay. The receptor in vitro translated in rabbit reticulocyte lysate was rapidly degraded by protease, produced major bands of about 34 kDa and showed a high affinity for estradiol. In a wheat germ translation system, the receptor was more slowly digested. Two soluble co-existing conformations were evident by different degradation patterns and estradiol binding. Our data show that differences in the translation machinery may result in alternative conformations of the receptor with distinct sterol binding properties. These studies suggest that components of the cellular translation machinery itself might influence the protein folding pathways and the relative abundance of different receptor conformers. (C) 2007 Published by Elsevier Inc

Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients

BACKGROUND: The study of genetic variants alone is not enough to explain a complex disease like cancer. Alterations in DNA methylation patterns have been associated with different types of tumor. In order to detect markers of susceptibility for the development of cutaneous melanoma and breast cancer in the Uruguayan population, we integrated genetic and epigenetic information of patients and controls. METHODS: We performed two case-control studies that included 49 individuals with sporadic cutaneous melanoma and 73 unaffected controls, and 179 women with sporadic breast cancer and 209 women controls. We determined the level of global leukocyte DNA methylation using relative quantification of 5mdC by HPLC, and we compared methylation levels between cases and controls with nonparametric statistical tests. Since the Uruguayan population is admixed and both melanoma and breast cancer have very high incidences in Uruguay compared to other populations, we examined whether individual ancestry influences global leucocyte DNA methylation status. We carried out a correlation analysis between the percentage of African, European and Native American individual ancestries, determined using 59 ancestry informative markers, and global DNA methylation in all participants. RESULTS: We detected global DNA hypomethylation in leukocytes of melanoma and breast cancer patients compared with healthy controls (p < 0.001). Additionally, we found a negative correlation between African ancestry and global DNA methylation in cancer patients (p <0.005). CONCLUSIONS: These results support the potential use of global DNA methylation as a biomarker for cancer risk. In addition, our findings suggest that the ancestral genome structure generated by the admixture process influences DNA methylation patterns, and underscore the importance of considering genetic ancestry as a modifying factor in epigenetic association studies in admixed populations such as Latino ones.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]