Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

2011 Trends in carbohydrate, fat, and protein intakes and association with energy intake in normal-weight, overweight, and obese individuals: 1971–2006

ABSTRACT Background: The prevalence of obesity in the United States has increased dramatically. Objective: The aim of this study was to determine trends in carbohydrate, fat, and protein intakes in adults and their association with energy intake by using data from the National Health and Nutrition Examination Survey (NHANES)-a representative sample of the US population. Design: Data on adults aged 20-74 y from the first NHANES (NHANES I, 1971(NHANES I, -1975; n = 13,106) were compared with data from NHANES 2005-2006 (n = 4381). Normal weight was defined as a body mass index (BMI; in kg/m 2 ) of 19 to ,25, overweight as a BMI of 25 to ,30, and obese as a BMI of 30. Carbohydrate, fat, and protein intakes were obtained by dietary recall. Regression analyses were adjusted for potential confounders. Results: The prevalence of obesity increased from 11.9% to 33.4% in men and from 16.6% to 36.5% in women. The percentage of energy from carbohydrates increased from 44.0% to 48.7%, the percentage of energy from fat decreased from 36.6% to 33.7%, and the percentage of energy from protein decreased from 16.5% to 15.7%. Trends were identical across normal-weight, overweight, and obese groups. Energy intake increased substantially in all 3 BMI groups. In NHANES 2005-2006, a 1% increase in the percentage of energy from protein was associated with a decrease in energy intake of 32 kcal (substituted for carbohydrates) or 51 kcal (substituted for fat). Similar findings were seen across all BMI categories, in men and women, and in NHANES I. Conclusions: Energy intake and the prevalence of obesity have increased dramatically. Dietary interventions should focus on decreasing energy intake and potentially by substituting protein for fat or carbohydrates. Am J Clin Nut

Physical Activity Patterns in the National Weight Control Registry

Objective: The National Weight Control Registry (NWCR) was established in 1993 to examine the characteristics of those who are successful at weight loss: individuals maintaining a 13.6-kg weight loss for \u3e1 year. The size of the registry has increased substantially since the early descriptions of this group a decade ago. The purpose of this study was to describe in detail the weekly physical activity habits of NWCR members, to examine the relationship between amount of activity and demographic characteristics, and to determine if changes in activity parameters have occurred over time. Methods and Procedures: Participants were 887 men and 2,796 women who enrolled in the NWCR between 1993 and 2004. Physical activity was evaluated at registry entry using the Paffenbarger Physical Activity Questionnaire. Results: NWCR entrants report an average of 2,621 ± 2,252 kcal/week in physical activity. There is considerable variability in the amount of activity reported: 25.3% report 3,000 kcal/week. Activity level on registry entry is related to the magnitude but not the duration of weight loss. The amount of activity reported by men has decreased over time while no significant change was observed in women. Changes in the types of activities most frequently reported were also observed. Discussion: Overall, NWCR participants are an extremely physically active group. However, the amount of activity reported is highly variable, making it difficult to develop a single recommendation for the optimum amount of physical activity for weight loss maintenance. A better understanding of individual-specific determinants of how much activity is required for weight loss maintenance ought to be a high research priority

Changing Trends in the Prevalence and Disparities of Obesity and Other Cardiovascular Disease Risk Factors in Three Racial/Ethnic Groups of USA Adults

Objectives. To examine trends in the prevalence and disparities of traditional cardiovascular disease (CVD) risk factors among the major race/ethnic groups in the USA: non-Hispanic Whites (NHWs), non-Hispanic Blacks (NHBs), and Mexican Americans (MAs). Methods. We used cross-sectional trend analysis in women and men aged 25–84 years participating in the NHANES surveys, years 1988–1994 (n=14,341) and 1999–2004 (n=12,360). Results. The prevalence of obesity and hypertension increased significantly in NHW and NHB, both in men and women; NHB had the highest prevalence of obesity and hypertension in each time period. Diabetes prevalence showed a nonsignificant increasing trend in all groups and was higher in MA in both periods. Smoking significantly decreased in NHW men and NHB, the latter with the largest decline although the highest prevalence in each period; no changes were noted in MA, who had the lowest prevalence in both periods. Race/ethnic CVD risk factors disparities widened for obesity and hypercholesterolemia, remained unchanged for diabetes and hypertension, and narrowed for smoking. Conclusions. The increasing prevalence of obesity and hypertension underscores the need for better preventive measures, particularly in the NHB group that exhibits the worst trends. The decline in smoking rates may offset some of these unfavorable trends