RESUMO
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.
Assuntos
Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/epidemiologia , Carcinoma de Células Escamosas do Esôfago/genética , Mutação , Desaminases APOBEC/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Aldeído-Desidrogenase Mitocondrial/genética , Brasil/epidemiologia , China/epidemiologia , Feminino , Humanos , Incidência , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Proteína Supressora de Tumor p53/genética , Reino Unido/epidemiologia , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Existing evidence suggests the visceral fat is more metabolically active than subcutaneous fat. We aimed to investigate the value of subcutaneous (SAT) and visceral adipose tissue thickness (VAT) for prediction of gallstone disease (GSD) in general population by focus on gender differences and comparison with body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR). MATERIAL AND METHODS: In this cross-sectional survey, 1,494 subjects (51.4 % men), aged above 50, randomly selected from Golestan Cohort Study residing in Gonbad City, Iran, underwent anthropometric measurements and abdominal ultrasonography. RESULTS: Prevalence of GSD was 17.8% (95% CI 15.9-19.8). Following adjustment for age and then other potential risk factors, all obesity indices, except for SAT, were associated with GSD in women with the highest odds ratio observed in WHtR (OR 1.52, 95% CI 1.22-1.89). In contrast, WHR was the only associated index in men (OR 1.49, 95% CI 1.08-2.06). The trend of increasing obesity measures across the quartiles with the risk of GSD was significant in subgroups of WHtR and BMI in women and WHR in men. No significant association was found between SAT and GSD in men or women. CONCLUSIONS: The best anthropometric indicators of the risk of GSD may differ by gender. In men, WHR might be the only preferred index to estimate risk of GSD. WHtR, WHR, VAT and BMI are associated with GSD risk in women, although WHtR might better explain this risk. SAT is the poor indicator for identifying subjects with GSD in both genders.