RESUMEN
BACKGROUND: Large rearrangements in BRCA1 and BRCA2 occur in a small percentage (< 1%) of patients tested for hereditary breast (BC) and ovarian cancer. It is unclear what factors predict BRACAnalysis Large Rearrangement Test (BART) positivity. METHODS: Data from 6 centers were included in this analysis. Individuals with negative Comprehensive BRACAnalysis tested for BART were included. RESULTS: From 1300 individuals, 42 (3.2%) were BART positivity. Factors positively associated with BART positivity were Myriad score, first-degree relatives with BC, infiltrating BC with ductal carcinoma in situ, younger age at BC diagnosis, estrogen receptor-negative BC for both the first and second BC, and Latin American/Caribbean ethnicity. Presence of unilateral BC was inversely associated with BART positivity. Several analyses were performed on the variables available to find the model that best predicts for BART positivity. The BART predictive model, including first BC, ovarian cancer, primary maternal ancestry being Latin America/Caribbean, number of first-degree relatives with BC of 1 or more versus 0, and family history of prostate and pancreatic cancer, had good predictive ability with an area under the curve of 0.77. CONCLUSIONS: Several factors are significantly associated with BART positivity. Among them we have found that Latin American/Caribbean ancestry, Myriad score, first degree relatives with BC, younger age at BC diagnosis, estrogen receptor-negative status of BC, and infiltrating ductal carcinoma with ductal carcinoma in situ features are significantly associated with BART positivity. A BART predictive model may help in a clinical setting.
Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Proteínas Portadoras/genética , Exones/genética , Eliminación de Gen , Duplicación de Gen , Genes BRCA1 , Genes BRCA2 , Neoplasias Ováricas/genética , Adenocarcinoma Mucinoso/genética , Adulto , Negro o Afroamericano/genética , Negro o Afroamericano/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/etnología , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/genética , Carcinoma Intraductal no Infiltrante/genética , Carcinoma Lobular/genética , Región del Caribe/etnología , Europa (Continente)/etnología , Femenino , Predisposición Genética a la Enfermedad , Hispánicos o Latinos/genética , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Judíos/genética , Judíos/estadística & datos numéricos , Persona de Mediana Edad , Mutación , Neoplasias Ováricas/etnología , Valor Predictivo de las Pruebas , Riesgo , Factores de Transcripción , Estados Unidos , Población Blanca/genética , Población Blanca/estadística & datos numéricosRESUMEN
Chronic deficiencies in the complement pathway proteins are associated with an increased risk of meningococcal disease. Such deficiencies are caused by primary congenital immunodeficiency of a complement protein, properdin or mannose binding lectin, or are secondary to consumption of complement by systemic lupus erythematosus (SLE) or membranoproliferative glomerulonephritis (MPGN). Whatever the cause, the complement deficiency is always chronic. Here we report a case of meningococcal disease (MCD) in a child with a transient complement deficiency (CD), caused by post-streptococcal glomerulonephritis (PSGN).