Grant Number:	5R01CA119171-17 Interpret this number
Primary Investigator:	Neuhouser, Marian
Organization:	Fred Hutchinson Cancer Center
Project Title:	Nutrition and Physical Activity Assessment Study
Fiscal Year:	2023

PROJECT SUMMARY This competing renewal of CA119171-12 “Nutrition and Physical Activity Assessment Study” (NPAAS) continues to focus on the development of novel dietary biomarkers and application of these biomarkers to investigations of diet and cancer, cardiovascular disease and type 2 diabetes risk in the Women’s Health Initiative (WHI) cohorts of postmenopausal U.S. women. Our work uses objective biomarkers of nutrients, foods and dietary patterns using blood and urine biospecimens collected in controlled feeding studies where types and quantities of foods and beverages are known. The dietary biomarkers can be used as stand-alone assessments of diet or, as emphasized in this proposal, they may be able to be extended to make them suitable for inexpensive disease association applications using a regression calibration approach. Progress has been made on the identification of objective measures of some dietary variables for public health applications, but there is still limited use of high-dimensional platforms (e.g., metabolomics in blood and urine) for this purpose. Further development is also needed for discovery and evaluation of stable isotope biomarkers of important dietary components, such as meat, fish and added sugars, where there are likely links to chronic disease risk. The discovery and validation of objective measures of healthy dietary patterns is another gap that we will address. In this cycle of funding, we propose to contribute to these research areas and to carry out generalizability studies toward extending these biomarker-intake results to diverse populations beyond the WHI. Our specific aims are: 1) To develop further and evaluate candidate biomarkers of foods, nutrients and other dietary compounds informed by data from the NPAAS feeding study (n=153) and to apply biomarkers meeting our prespecified NPAAS-derived criteria to examine associations with risk of cancer, cardiovascular disease and type 2 diabetes in WHI cohorts of postmenopausal women (n=161,808); 2) To measure serum carbon and nitrogen isotope ratios and amino acid carbon isotope ratios as biomarkers of fish/seafood, animal protein and added sugars in the NPAAS Observational Study (n=450) and to apply these measures to test associations with risk of cancer, cardiovascular disease and diabetes in WHI cohorts; 3) To identify and evaluate candidate dietary biomarkers of healthy eating patterns (e.g., Healthy Eating Index, Alternative Mediterranean Diet Score) for testing associations between these eating patterns with the same set of chronic diseases in WHI cohorts; and 4) To test, using blood and urine metabolomics, the generalizability of novel metabolomic biomarkers identified in the NPAAS feeding study to diverse study populations in two controlled feeding studies. Our productive research team is expected to make additional, innovative contributions to nutritional epidemiology research and more broadly to chronic disease prevention research. Our research builds on the understanding that biomarkers of dietary intake, as stand-alone exposures or as tools to calibrate self-report, are crucial to the development of reliable information on the effects of diet on chronic disease risk.




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Metabolite Predictors of Breast and Colorectal Cancer Risk in the Women's Health Initiative.
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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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USING SIMULTANEOUS REGRESSION CALIBRATION TO STUDY THE EFFECT OF MULTIPLE ERROR-PRONE EXPOSURES ON DISEASE RISK UTILIZING BIOMARKERS DEVELOPED FROM A CONTROLLED FEEDING STUDY.
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Biomarker-assessed total energy intake and its cohort study association with all-cause mortality in postmenopausal females.
Authors: Prentice R.L. , Aragaki A.K. , Zheng C. , Manson J.E. , Tinker L.F. , Ravelli M.N. , Mossavar-Rahmani Y. , Wallace R.B. , Tooze J.A. , Johnson K.C. , et al. .
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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.
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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.
Authors: Prentice R.L. , Vasan S. , Tinker L.F. , Neuhouser M.L. , Navarro S.L. , Raftery D. , Gowda G.N. , Pettinger M. , Aragaki A.K. , Lampe J.W. , et al. .
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Total energy expenditure as assessed by doubly labeled water and all-cause mortality in a cohort of postmenopausal women.
Authors: Prentice R.L. , Aragaki A.K. , Manson J.E. , Schoeller D.A. , Tinker L.F. , Mossavar-Rahmani Y. , Wallace R.B. , LaMonte M.J. , Tooze J.A. , Johnson K.C. , et al. .
Source: The American Journal Of Clinical Nutrition, 2023 May; 117(5), p. 955-963.
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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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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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Demographic, Health and Lifestyle Factors Associated with the Metabolome in Older Women.
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Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure.
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Using Controlled Feeding Study for Biomarker Development in Regression Calibration for Disease Association Estimation.
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RE: Systemic or vaginal hormone therapy after early breast cancer: a Danish observational cohort study.
Authors: Chlebowski R.T. , Aragaki A.K. , Pan K. .
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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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Variation in human water turnover associated with environmental and lifestyle factors.
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Mortality Associated with Healthy Eating Index Components and an Empirical-Scores Healthy Eating Index in a Cohort of Postmenopausal Women.
Authors: Prentice R.L. , Aragaki A.K. , Van Horn L. , Thomson C.A. , Tinker L.F. , Manson J.E. , Mossavar-Rahmani Y. , Huang Y. , Zheng C. , Beresford S.A. , et al. .
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Variability in energy expenditure is much greater in males than females.
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Adherence to the American Cancer Society Guidelines on nutrition and physical activity for cancer prevention and obesity-related cancer risk and mortality in Black and Latina Women's Health Initiative participants.
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Human total, basal and activity energy expenditures are independent of ambient environmental temperature.
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Human total, basal and activity energy expenditures are independent of ambient environmental temperature.
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EPub date: 2022-06-28 00:00:00.0.
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Authors: Chlebowski R.T. , Aragaki A.K. , Pan K. .
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Criteria for Acceptable Dietary Intake Biomarkers.
Authors: Prentice R.L. .
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Menopausal Hormone Therapy and Breast Cancer.
Authors: Chlebowski R.T. , Manson J.E. .
Source: Cancer Journal (sudbury, Mass.), 2022 May-Jun 01; 28(3), p. 169-175.
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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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Biomarkers for Components of Dietary Protein and Carbohydrate with Application to Chronic Disease Risk in Postmenopausal Women.
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Source: The Journal Of Nutrition, 2022-04-01 00:00:00.0; 152(4), p. 1107-1117.
PMID: 35015878
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Biomarker-calibrated Red and Combined Red and Processed Meat Intakes with Chronic Disease Risk in a Cohort of Postmenopausal Women.
Authors: Zheng C. , Pettinger M. , Gowda G.A.N. , Lampe J.W. , Raftery D. , Tinker L.F. , Huang Y. , Navarro S.L. , O'Brien D.M. , Snetselaar L. , et al. .
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Biomarker-Based Methods and Study Designs to Calibrate Dietary Intake for Assessing Diet-Disease Associations.
Authors: Huang Y. , Zheng C. , Tinker L.F. , Neuhouser M.L. , Prentice R.L. .
Source: The Journal Of Nutrition, 2022-03-03 00:00:00.0; 152(3), p. 899-906.
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Four-day food record macronutrient intake, with and without biomarker calibration, and chronic disease risk in postmenopausal women.
Authors: Prentice R.L. , Pettinger M. , Neuhouser M.L. , Raftery D. , Zheng C. , Gowda G.A.N. , Huang Y. , Tinker L.F. , Howard B.V. , Manson J.A.E. , et al. .
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Total energy expenditure is repeatable in adults but not associated with short-term changes in body composition.
Authors: Rimbach R. , Yamada Y. , Sagayama H. , Ainslie P.N. , Anderson L.F. , Anderson L.J. , Arab L. , Baddou I. , Bedu-Addo K. , Blaak E.E. , et al. .
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PMID: 35013190
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Reply to WC Willett and D Ludwig.
Authors: Prentice R.L. , Howard B.V. , Van Horn L. , Manson J.E. , Chlebowski R.T. .
Source: The American Journal Of Clinical Nutrition, 2021-12-01 00:00:00.0; 114(6), p. 2120-2122.
PMID: 36017654
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Physical activity and fat-free mass during growth and in later life.
Authors: Westerterp K.R. , Yamada Y. , Sagayama H. , Ainslie P.N. , Andersen L.F. , Anderson L.J. , Arab L. , Baddou I. , Bedu-Addo K. , Blaak E.E. , et al. .
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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.
Authors: Neuhouser M.L. , Pettinger M. , Lampe J.W. , Tinker L.F. , George S.M. , Reedy J. , Song X. , Thyagarajan B. , Beresford S.A. , Prentice R.L. .
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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.
Authors: Tinker L.F. , Huang Y. , Johnson K.C. , Carbone L.D. , Snetselaar L. , Van Horn L. , Manson J.E. , Liu S. , Mossavar-Rahmani Y. , Prentice R.L. , et al. .
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An approximate quasi-likelihood approach for error-prone failure time outcomes and exposures.
Authors: Boe L.A. , Tinker L.F. , Shaw P.A. .
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EPub date: 2021-06-22 00:00:00.0.
PMID: 34519082
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Energy compensation and adiposity in humans.
Authors: Careau V. , Halsey L.G. , Pontzer H. , Ainslie P.N. , Andersen L.F. , Anderson L.J. , Arab L. , Baddou I. , Bedu-Addo K. , Blaak E.E. , et al. .
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EPub date: 2021-08-26 00:00:00.0.
PMID: 34453886
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Daily energy expenditure through the human life course.
Authors: Pontzer H. , Yamada Y. , Sagayama H. , Ainslie P.N. , Andersen L.F. , Anderson L.J. , Arab L. , Baddou I. , Bedu-Addo K. , Blaak E.E. , et al. .
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