RESUMEN
The distribution of BRCA1/2 germline mutations in breast/ovarian cancer (BC/OC) families varies among different populations. In the Chilean population, there are only two reports of mutation analysis of BRCA1/2, and these included a low number of BC and/or OC patients. Moreover, the prevalence of BRCA1/2 genomic rearrangements in Chilean and in other South American populations is unknown. In this article, we present the mutation-detection data corresponding to a set of 326 high-risk families analyzed by conformation-sensitive gel electrophoresis and heteroduplex analysis. To determine the contribution of BRCA1/2 LGRs in Chilean BC patients, we analyzed 56 high-risk subjects with no pathogenic BRCA1/2 point mutations. Germline BRCA1/2 point mutations were found in 23 (7.1%) of the 326 Chilean families. Families which had at least three BC and/or OC cases showed the highest frequency of mutations (15.9%). We identified 14 point pathogenic mutations. Three recurrent mutations in BRCA1 (c.187_188delAG, c.2605_2606delTT, and c.3450_3453delCAAG) and three in BRCA2 (c.4969_4970insTG, c.5374_5377delTATG, and c.6503_6504delTT) contributed to 63.6 and 66.7% of all the deleterious mutations of each gene, which may reflect the presence of region-specific founder effects. Taken together BRCA1/2 recurrent point mutations account for 65.2% (15/23) of the BRCA1/2 (+) families. No large deletions or duplications involving BRCA1/2 were identified in a subgroup of 56 index cases negative for BRCA1/2 point mutations. Our study, which is the largest conducted to date in a South American population, provides a comprehensive analysis on the type and distribution of BRCA1/2 mutations and allelic variants.
Asunto(s)
Neoplasias de la Mama Masculina/genética , Neoplasias de la Mama/genética , Genes BRCA1 , Genes BRCA2 , Neoplasias Ováricas/genética , Mutación Puntual , Adulto , Chile , Exones , Salud de la Familia , Femenino , Efecto Fundador , Reordenamiento Génico , Humanos , Intrones , Masculino , Persona de Mediana Edad , RiesgoRESUMEN
The double-strand break (DSB) DNA repair pathway has been implicated in breast cancer (BC). RAD51 and its paralogs XRCC3 and RAD51D play an important role in the repair of DSB through homologous recombination (HR). Some polymorphisms including XRCC3-Thr241Met, RAD51-135G>C, and RAD51D-E233G have been found to confer increased BC susceptibility. In order to detect novel mutations that may contribute to BC susceptibility, 150 patients belonging to 150 Chilean BRCA1/2-negative families were screened for mutations in XRCC3. No mutations were detected in the XRCC3 gene. In addition, using a case-control design we studied the XRCC3-Thr241Met, and RAD51D-E233G polymorphisms in 267 BC cases and 500 controls to evaluate their possible association with BC susceptibility. The XRCC3 Met/Met genotype was associated with an increased BC risk (P = 0.003, OR = 2.44 [95%CI 1.34-4.43]). We did not find an association between E233G polymorphism and BC risk. We also analyzed the effect of combined genotypes among RAD51-135G>C, Thr241Met, and E233G polymorphisms on BC risk. No interaction was observed between Thr241Met and 135G>C. The combined genotype Thr/Met-E/G was associated with an increased BC risk among women who (a) have a family history of BC, (b) are BRCA1/2-negative, and (c) were <50 years at onset (n = 195) (P = 0.037, OR = 10.5 [95%CI 1.16-94.5]). Our results suggested that the variability of the DNA HR repair genes XRCC3 and RAD51D may play a role in BC risk, but this role may be underlined by a mutual interaction between these genes. These findings should be confirmed in other populations.
Asunto(s)
Neoplasias de la Mama/genética , Roturas del ADN de Doble Cadena , Reparación del ADN/genética , Proteínas de Unión al ADN/genética , Polimorfismo Genético/genética , Adulto , Anciano , Neoplasias de la Mama/epidemiología , Estudios de Casos y Controles , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , América del Sur/epidemiologíaAsunto(s)
Isquemia Encefálica/patología , Encéfalo/patología , Anciano , Edema Encefálico , Sustancia Gris , Humanos , Masculino , Sustancia BlancaRESUMEN
El número de estudiantes universitarios que presentan un endeudamiento temprano se ha incrementado en los últimos años, lo que representa un riesgo potencial para su estabilidad financiera. La presente investigación analiza la validez factorial de la Escala de Actitudes hacia el Endeudamiento (Denegri et al., 1999) y determina la existencia de tipología de perfiles actitudinales hacia el endeudamiento, en una muestra de 984 estudiantes universitarios chilenos con edades entre 18 y 25 años. Los resultados señalan la presencia de dos factores independientes denominados Hedonismo y Austeridad, a partir de los cuales se determinaron cuatro perfiles de actitudes hacia el endeudamiento llamados: austero, difuso, hedonista y ambivalente, que podrían estar a la base de comportamientos de aceptación o rechazo del endeudamiento.
The number of university students who present an early indebtedness has increased in the last years, which represents a potential risk for his financial stability. This study examined validity factorial of the Scale of Attitudes toward the Indebtedness (Denegri et al., 1999) and determines the existence of profile attitudinal typology towards the indebtedness in a sample of 984 university Chilean students with ages between 18 and 25 years. The results indicate the presence of two independent factors named Hedonism and Austerity, from which four profiles of attitudes decided towards the indebtedness named: austere, diffuse, hedonistic and ambivalent those who might be to the base of his behaviors of acceptance or rejection of the indebtedness.