RESUMEN
Esophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence that is not fully explained by known lifestyle and environmental risk factors. It has been speculated that an unknown exogenous exposure(s) could be responsible. Here we combine the fields of mutational signature analysis with cancer epidemiology to study 552 ESCC genomes from eight countries with varying incidence rates. Mutational profiles were similar across all countries studied. Associations between specific mutational signatures and ESCC risk factors were identified for tobacco, alcohol, opium and germline variants, with modest impacts on mutation burden. We find no evidence of a mutational signature indicative of an exogenous exposure capable of explaining differences in ESCC incidence. Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)-associated mutational signatures single-base substitution (SBS)2 and SBS13 were present in 88% and 91% of cases, respectively, and accounted for 25% of the mutation burden on average, indicating that APOBEC activation is a crucial step in ESCC tumor development.
Asunto(s)
Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/epidemiología , Carcinoma de Células Escamosas de Esófago/genética , Mutación , Desaminasas APOBEC/genética , Adulto , Anciano , Anciano de 80 o más Años , Aldehído Deshidrogenasa Mitocondrial/genética , Brasil/epidemiología , China/epidemiología , Femenino , Humanos , Incidencia , Irán/epidemiología , Masculino , Persona de Mediana Edad , Proteína p53 Supresora de Tumor/genética , Reino Unido/epidemiología , Secuenciación Completa del GenomaRESUMEN
Caecal biopsy specimens from Jamaican children with the Trichuris dysentery syndrome (TDS) and age matched Jamaican controls were investigated by immunohistochemistry and by light microscopy. Biopsy specimens from all children (with TDS and controls) showed a mild to moderate increase in inflamatory cells. Except in the vicinity of the worm, where the epithlium was flattened, there was no other epithelial abnormality. Compared with controls, children with TDS had increased IgM lamina propria plasma cells and decreased intaepithelial T cells. There was also an increase in crypt epithelial cells proliferation. Lamina propia T cells (both activated and non-activated) were no more common in children with the Trichuris syndrome than controls. Epithelial cell HLA-DR and VLA-1 expression (which are increased in other colitides) were the same in both groups. Despite the presence of large worm burdens and chronic dysentery, therefore, only minor changes were seen in the caecal mucosa of children with TDS. (AU)