Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10−14, odds ratio = 0.86, 95% confidence interval = 0.82–0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Estudo antropométrico e dietético de nadadores competitivos de áreas metropolitanas da região sudeste do Brasil

Com o objetivo de caracterizar os ábitos alimentares de nadadores competitivos de dois clubes das cidades do Rio de Janeiro e de São Paulo, foram estudados atletas, 30 homens e 37 mulheres pertencentes às equipes juvenil (15-17 anos) e seniors (18-25 anos). Concomitantemente à avaliação antropométrica, foi feito o inquérito alimentar mediante os métodos de registro alimentar, recordatório de 24 horas e freqüência de consumo alimentar. Os resultados mostraram semelhança antropométrica entre as duas faixas etárias para cada um dos sexos, semelhança dos alimentos prevalentemente ingeridos com aqueles referidos pela população da área metropolitana das duas cidades e semelhança entre os suplementos alimentares ingeridos pelos atletas dos dois clubes. A ingestão calórica observada foi quase o dobro da referida para a população daquelas localidades, mas equivalente à descrita para nadadores de outros países. Os lanches, entre refeições, contribuíram com 25-28% da ingestão calórica global e a maior contribuição energética alimentar foi dada pelo grupo de cereais. Apesar de contribuir com quase 50% do aporte calórico diário, a ingestão glicídica foi menor que a recomendada para atletas competitivos (55-60%). A ingestão protéica de 2,5-3,0 g/kg/dia superou em 100% o valor recomendado para atletas e ultrapassou os 15% na participação calórica diária. A ingestão lipídica foi considerada elevada, particularmente a de gordura saturada. O aporte de micronutrientes foi acima do referido para as populações locais em função da ingestão calórica elevada, mas mostrou-se relativamente inadequado em magnésio, ferro e vitaminas A e D. Conclui-se que o padrão alimentar dos nadadores estudados não difere, muito, do da população local, distinguindo-se pelo elevado e freqüente consumo de alimentos energéticos, maior no sexo masculino que no feminino.The daily food intake and alimentary frequency of competitive swimmers of two clubs representative of the two largest cities in Brazil (S.Paulo and Rio de Janeiro) were studied. The 30 males and 37 females studied belonged to the swimming categories junior (15-17 yrs old) and senior (18-25 yrs old). Food intake obtained from self-register and 24 hour-recall showed similar results and therefore the 24 hour-recall was used for comparisons with the literature. Ages within both sexes were anthropometrically similar. The most frequently eaten foodstaffs were similar to those quoted by the metropolitan population of the respective areas. Moroever, the athletes from both cities reported similar food-supplements. The energy intake was found to average almost double the estimated value for the respective metropolitan populations, but were similar to results obtained for swimmers all over the world. Snacks between meals supplied 25-28% of the overall energy intake. The main caloric source were cereals. However, despite their contribution of almost 50% of the total energy intake, carbohydrates attained a level of only 55-60% of that recommended for competitive athletes. on the other hand, the protein intake found (2.5-3.0 g/kg/day) exceeded the recommended values by 100%. The fat intake particularly of satured fat, was also considered high. The swimmers' intake of micronutrients was well abone that quoted by the regular population of these metropolitan areas, when related to the caloric intake, but the values of Mg, Fe and vitamins A and D were somecohot lower than those recommended. This is due to the higers energy intake of the swimmers. From these overall results it may be concluded that the alimentary pattern of the swimmers studied does not differ greatly from that of the local population, being distinguished by its higher and more frequent intake of caloric foods rather than by its qualitative aspects