RESUMEN
Three inherited autosomal dominant conditions-BRCA-related hereditary breast and ovarian cancer (HBOC), Lynch syndrome (LS) and familial hypercholesterolemia (FH)-have been termed the Centers for Disease Control and Prevention Tier 1 (CDCT1) genetic conditions, for which early identification and intervention have a meaningful potential for clinical actionability and a positive impact on public health1. In typical medical practice, genetic testing for these conditions is based on personal or family history, ethnic background or other demographic characteristics2. In this study of a cohort of 26,906 participants in the Healthy Nevada Project (HNP), we first evaluated whether population screening could efficiently identify carriers of these genetic conditions and, second, we evaluated the impact of genetic risk on health outcomes for these participants. We found a 1.33% combined carrier rate for pathogenic and likely pathogenic (P/LP) genetic variants for HBOC, LS and FH. Of these carriers, 21.9% of participants had clinically relevant disease, among whom 70% had been diagnosed with relevant disease before age 65. Moreover, 90% of the risk carriers had not been previously identified, and less than 19.8% of these had documentation in their medical records of inherited genetic disease risk, including family history. In a direct follow-up survey with all carriers, only 25.2% of individuals reported a family history of relevant disease. Our experience with the HNP suggests that genetic screening in patients could identify at-risk carriers, who would not be otherwise identified in routine care.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Pruebas Genéticas , Genética de Población , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Hiperlipoproteinemia Tipo II/genética , Adolescente , Adulto , Anciano , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Femenino , Tamización de Portadores Genéticos/métodos , Síndrome de Cáncer de Mama y Ovario Hereditario/diagnóstico , Síndrome de Cáncer de Mama y Ovario Hereditario/patología , Heterocigoto , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/patología , Persona de Mediana EdadRESUMEN
We observe a net beam excess of 8.7+/-6.3(stat)+/-2.4(syst) events, above 160 MeV, resulting from the charged-current reaction of nu(micro) and/or nu;(mu) on C and H in the LSND detector. No beam-related muon background is expected in this energy regime. Within an analysis framework of pi(0)-->nu(mu)nu;(mu), we set a direct upper limit for this branching ratio of Gamma(pi(0)-->nu(mu)nu;(mu))/Gamma(pi(0)-->all)<1.6 x 10(-6) at 90% confidence level.
