Grant Number:	2R01CA119171-09A1 Interpret this number
Primary Investigator:	Neuhouser, Marian
Organization:	Fred Hutchinson Cancer Research Center
Project Title:	Nutrition and Physical Activity Assessment Study (NPAAS)
Fiscal Year:	2016

¿ DESCRIPTION (provided by applicant): This competing renewal of CA119171, "Nutrition and Physical Activity Assessment Study" (NPAAS), continues to focus the use of biomarkers and regression calibration models to understand better the relationship between diet, physical activity and chronic disease risk in postmenopausal women. Our work uses objective biomarkers in regression calibration models to correct self-report data for random and systematic measurement biases. This work has provided evidence for strong positive associations of energy intake, and strong inverse associations of activity-related energy expenditure (AREE), with chronic disease risk; these associations were absent without measurement error correction. To date, suitable quantitative biomarkers have been available for few diet components (e.g. total energy, protein, potassium, sodium) and physical activity (AREE). For this grant funding period, we will extend our work by using innovative metabolomics profiling in blood and urine specimens to characterize food and nutrient intake. Metabolomics offers the possibility to advance the field of nutritional epidemiology in a manner not been possible with individual biomarkers since metabolomics uniquely accounts for dietary exposures in an integrated manner and explains > 50% of the variation in nutrient intake. Our specific aims are: (1) To obtain serum and 24-hour urine metabolomic profiles for n=450 WHI-NPAAS participants who have stored blood and urine specimens from a previous project cycle. To use these profiles to calculate intake values for each nutritional variable for which a biomarker is established in our recently completed NPAAS feeding study. To use the resulting biomarker-based intake values to develop calibration equations for each nutritional variable using previously collected food frequency questionnaire, 4-day food record and 24-hour dietary recalls, as well as participant characteristics, from these 450 women. (2) To use the calibration equations developed in Aim 1 to estimate intake throughout WHI cohorts for each nutritional variable with suitable biomarkers. To conduct a series of analyses examining the association of metabolomics- calibrated nutrient intake with risk of major cancers, cardiovascular diseases and diabetes in WHI cohorts, where self-reported dietary intake and other key data are available at baseline for 161,000 postmenopausal women. (3) To use serum and spot urine metabolomic profiles to directly estimate intake for each nutritional variable having a suitable biomarker, in subset of about 12,000 WHI women with both stored blood and urine. Profiles will be obtained for n=708 adjudicated cancers (breast, colorectal, ovarian and endometrial) and n=708 controls. These analyses will assess novel nutrition and metabolite cancer associations without use of dietary self-report data. (4) To examine blood- and urine-based metabolomic profiles more broadly in relation to cancer risk in the Aim 3 case-control sample without regard to the role of specific metabolites in nutrient biomarker specification. Our highly productive research team is expected to make additional, innovative contributions in nutritional epidemiology and more broadly in chronic disease prevention research.




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Estrogen Plus Progestin and Colorectal Cancer: Long-Term Findings From the Women's Health Initiative Randomized Clinical Trial.
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Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women's Health Initiative.
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Intake Biomarkers for Nutrition and Health: Review and Discussion of Methodology Issues.
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Randomized trials of estrogen-alone and breast cancer incidence: a meta-analysis.
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Biomarker-assessed total energy intake and its cohort study association with all-cause mortality in postmenopausal females.
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Measuring diet by metabolomics: a 14-d controlled feeding study of weighed food intake.
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Reply to W Willett.
Authors: Prentice R.L. , Neuhouser M.L. , Chlebowski R.T. .
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Diet and Chronic Disease Research in the Women's Health Initiative.
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Bilateral Oophorectomy and Colorectal Cancer Incidence and Mortality in the Women's Health Initiative.
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Long-term breast cancer incidence trends by mammography, obesity, and menopausal hormone therapy.
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Metabolomics Biomarkers for Fatty Acid Intake and Biomarker-Calibrated Fatty Acid Associations with Chronic Disease Risk in Postmenopausal Women.
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Metabolomics-Based Biomarker for Dietary Fat and Associations with Chronic Disease Risk in Postmenopausal Women.
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Total energy expenditure as assessed by doubly labeled water and all-cause mortality in a cohort of postmenopausal women.
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Development and validation of new predictive equations for the resting metabolic rate of older adults aged ≥65 y.
Authors: Porter J. , Ward L.C. , Nguo K. , Davidson Z. , Gibson S. , Prentice R. , Neuhouser M.L. , Truby H. .
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Development and validation of new predictive equations for the resting metabolic rate of older adults aged ≥65 y.
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Enhancing Capacity for Food and Nutrient Intake Assessment in Population Sciences Research.
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Associations of Biomarker-Calibrated Healthy Eating Index-2010 Scores with Chronic Disease Risk and Their Dependency on Energy Intake and Body Mass Index in Postmenopausal Women.
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Regression calibration utilizing biomarkers developed from high-dimensional metabolites.
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Human total, basal and activity energy expenditures are independent of ambient environmental temperature.
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Criteria for Acceptable Dietary Intake Biomarkers.
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Menopausal Hormone Therapy and Breast Cancer.
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The Association of Predicted Resting Energy Expenditure with Risk of Breast Cancer among Postmenopausal Women in the Women's Health Initiative Cohort.
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Biomarker-Based Methods and Study Designs to Calibrate Dietary Intake for Assessing Diet-Disease Associations.
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Four-day food record macronutrient intake, with and without biomarker calibration, and chronic disease risk in postmenopausal women.
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Physical activity and fat-free mass during growth and in later life.
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Novel Application of Nutritional Biomarkers From a Controlled Feeding Study and an Observational Study to Characterization of Dietary Patterns in Postmenopausal Women.
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Estimating 24-Hour Urinary Excretion of Sodium and Potassium Is More Reliable from 24-Hour Urine Than Spot Urine Sample in a Feeding Study of US Older Postmenopausal Women.
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An approximate quasi-likelihood approach for error-prone failure time outcomes and exposures.
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EPub date: 2021-06-22 00:00:00.0.
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Energy compensation and adiposity in humans.
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Daily energy expenditure through the human life course.
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