RESUMO
It is not uncommon for cancer geneticists to be referred families with apparently Mendelian co-inheritance of breast and bowel cancer. Such families present a particular problem as regards the intensity of their screening for these diseases and the utility of genetic testing. Many 'breast-colon' cancer families probably result from chance clustering of two common cancers. Other 'breast-colon' cancer families may result from known cancer syndromes, such as hereditary breast-ovarian cancer or hereditary non-polyposis colon cancer, either by conferring a high risk of one cancer type and a slightly increased risk of the other, or through a predisposition to one of the two cancers and chance occurrence of the other. Anecdotally, however, many geneticists wonder about the existence of a distinct 'breast-colon cancer syndrome', since some families present good a priori evidence of genetic disease and yet cannot readily be accounted for by known genes or chance. The identification of unknown 'breast-colon cancer' genes is likely to be difficult, relying primarily on candidate gene analysis, including loci separately implicated in breast or colorectal cancer, or in other multiple cancer syndromes. Studies such as those on APC I1307K and CHEK2 1100delC may suggest the way forward for the identification of 'breast-colon cancer' genes.
Assuntos
Neoplasias da Mama/genética , Neoplasias Colorretais/genética , Heterogeneidade Genética , Predisposição Genética para Doença , Adulto , Quinase do Ponto de Checagem 2 , Feminino , Frequência do Gene , Genes APC , Humanos , Masculino , Mutação , Linhagem , Fenótipo , Proteínas Serina-Treonina Quinases/genéticaRESUMO
BACKGROUND: Juvenile polyposis syndrome (JPS) is characterised by gastrointestinal (GI) hamartomatous polyposis and an increased risk of GI malignancy. Juvenile polyps also occur in the Cowden (CS), Bannayan-Ruvalcaba-Riley (BRRS) and Gorlin (GS) syndromes. Diagnosing JPS can be problematic because it relies on exclusion of CS, BRRS, and GS. Germline mutations in the PTCH, PTEN and DPC4 (SMAD4) genes can cause GS, CS/BRRS, and JPS, respectively. AIMS: To examine the contribution of mutations in PTCH, PTEN, and DPC4 (SMAD4) to JPS. METHODS: Forty seven individuals from 15 families and nine apparently sporadic cases with JPS were screened for germline mutations in DPC4, PTEN, and PTCH. RESULTS: No patient had a mutation in PTEN or PTCH. Five different germline mutations were detected in DPC4; three of these were deletions, one a single base substitution creating a stop codon, and one a missense change. None of these patients had distinguishing clinical features. CONCLUSIONS: Mutations in PTEN and PTCH are unlikely to cause juvenile polyposis in the absence of clinical features indicative of CS, BRRS, or GS. A proportion of JPS patients harbour DPC4 mutations (21% in this study) but there remains uncharacterized genetic heterogeneity in JPS.
Assuntos
Polipose Adenomatosa do Colo/genética , Heterogeneidade Genética , Mutação em Linhagem Germinativa/genética , Proteínas Supressoras de Tumor , Polipose Adenomatosa do Colo/diagnóstico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Códon de Terminação/genética , Diagnóstico Diferencial , Feminino , Deleção de Genes , Testes Genéticos , Genótipo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto/genética , PTEN Fosfo-Hidrolase , Fenótipo , Monoéster Fosfórico Hidrolases/genéticaRESUMO
BACKGROUND: The study tested specific hypotheses that (a) there is an increased incidence of psychiatric disorders in asymptomatic heterozygotes for Huntington's disease (HD) compared with the normal homozygotes, and (b) there is an increased incidence of psychiatric disorders in the adult offspring of Huntington's disease patients compared with their partners. METHOD: A controlled study was made of 93 apparently healthy individuals (at 50% risk), who had given DNA samples for the predictive test, and 70 of their partners. Current and past psychopathology was assessed and compared with the DNA predictive test results based on linkage analyses. The results of psychiatric assessments of the two groups were compared. RESULTS: DNA test results were available for 53 subjects (of 93). Five subjects at risk for HD were omitted from the study. The asymptomatic heterozygotes (n = 20) showed no significant increase in the incidence of any psychiatric episode, depression, schizophrenia or behavioural disorder when compared with the normal homozygotes (n = 33). The whole tested group showed a significantly greater number of psychiatric episodes than their partners (n = 43). CONCLUSIONS: Asymptomatic HD gene carriers do not have a greater incidence of psychiatric disorders than the non-gene carriers born to a HD parent.
