RESUMEN
Hereditary non-polyposis colorectal cancer (HNPCC) may be the result of Lynch syndrome (LS) caused by mutations in mismatch repair (MMR) genes, a syndrome of unknown etiology called familial colorectal cancer type-X (FCCTX), or familial serrated neoplasia associated with the colorectal cancer (CRC) somatic BRAF mutation. To determine the cause of HNPCC in the founder population of the island of Newfoundland, we studied 37 families with LS and 29 families without LS who fulfilled the Amsterdam I criteria. In non-LS, four index CRCs were BRAF mutation positive, one of which was microsatellite instable. Geographic clustering of LS families caused by three different founder mutations in MSH2 was observed. Nine unique MMR mutations in four MMR genes were identified in single families distributed in different geographic isolates. The geographic distribution of non-LS was similar to LS. The coefficient of relatedness using genotype data was significantly higher for non-LS than for all CRC. Extensive genealogic investigation failed to connect non-LS families and in some clusters pathologic CRC heterogeneity was observed. We conclude that non-LS HNPCC may be a heterogeneous disorder with different pathogenic pathways, and that the geographic distribution is consistent with multiple different mutations in unknown CRC susceptibility gene(s).
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Anciano , Canadá , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Familia , Femenino , Efecto Fundador , Heterogeneidad Genética , Geografía Médica , Humanos , Masculino , Persona de Mediana Edad , Proteína 2 Homóloga a MutS/genética , Mutación , Vigilancia de la Población , Proteínas Proto-Oncogénicas B-raf/genética , Sistema de RegistrosRESUMEN
AIMS: To investigate antifungal activity produced by lactic acid bacteria (LAB) isolated from malted cereals and to determine if such LAB have the capacity to prevent fungal growth in a particular food model system. METHODS AND RESULTS: The effect of pH, temperature and carbon source on production of antifungal activity by four LAB was determined. Pediococcus pentosaceus was used to conduct a trial to determine if it is feasible to eliminate Penicillium expansum, the mould responsible for apple rot, using an apple model. Penicillium expansum was incapable of growth during the trial on apple-based agar plates inoculated with the antifungal-producing culture, whereas the mould did grow on apple plates inoculated with an LAB possessing no antifungal activity. CONCLUSION: Partial characterization of the antifungal compounds indicates that their activity is likely to be because of production of antifungal peptides. The trial conducted showed that the antifungal culture has the ability to prevent growth of the mould involved in apple spoilage, using apples as a model. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability of an LAB to prevent growth of Pen. expansum using the apple model suggests that these antifungal LAB have potential applications in the food industry to prevent fungal spoilage of food.