RESUMEN
AIMS: To determine the proportion of eligible patients with high-grade serous carcinoma of the ovary, fallopian tube or peritoneum discussed at gynaecological oncology multidisciplinary meetings (MDMs) in New Zealand and subsequently referred for genetic counselling and BRCA pathogenic variant testing. METHODS: Eligible cases were identified from Auckland, Wellington, Christchurch and Dunedin gynaecologic oncology MDM databases between 1 January 2015 to 31 December 2016. Patients who met the eligibility criteria for genetics referral were identified, and cross-referenced against genetic services databases to ascertain the rates of referrals received, the numbers attending appointments, genetic testing offered and range of results. RESULTS: During the two-year period, 205 patients were eligible for referral. Of these, 143 (70%) patients were referred for genetic counselling with 128 (90%) of this group recommended for BRCA pathogenic variant testing. Of the 126 who undertook the test, results were available for 120 (95%). Nineteen patients (16%) tested positive for a germline BRCA pathogenic variant. CONCLUSIONS: The New Zealand rate of referral to genetic counselling for women with high-grade serous cancer, (HGSC), of the ovary, fallopian tube or peritoneum diagnosed between 2015-2016 is encouraging when compared with others internationally. The rate of BRCA positive pathogenic variants is comparable to international data.
Asunto(s)
Neoplasias de la Mama , Genes BRCA1 , Genes BRCA2 , Servicios Genéticos/organización & administración , Neoplasias Ováricas , Aceptación de la Atención de Salud/estadística & datos numéricos , Pautas de la Práctica en Medicina , Derivación y Consulta , Adulto , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Femenino , Pruebas Genéticas/métodos , Humanos , Persona de Mediana Edad , Nueva Zelanda/epidemiología , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , Mejoramiento de la Calidad , Derivación y Consulta/organización & administración , Derivación y Consulta/normas , Derivación y Consulta/estadística & datos numéricosRESUMEN
Hereditary diffuse gastric cancer (HDGC) is a recently defined cancer syndrome caused by inactivating, heterozygous germline mutations in the gene for the cell-to-cell adhesion protein E-cadherin (CDH1). Here, we describe the search for CDH1 mutations in 10 newly identified gastric cancer families. Seven of 10 families met the clinical criteria for HDGC. Germline mutations were identified in four of these seven families and one family that was borderline for the clinical criteria. Of the mutations identified in the five new families, four were previously unreported and consisted of two frameshift and two donor splice site mutations. One splice site mutation occurred at the 100% conserved +1 position. The second splice site mutation occurred at the +5 position and was shown to lead to abnormal splicing. Additional CDH1 variants detected include the heterozygous -160 C-->A promoter polymorphism, which has previously been reported to be associated with decreased CDH1 transcription. We, however, found this polymorphism to be common in a control population, suggesting that a major role for this polymorphism in gastric cancer susceptibility is unlikely.