Ross L Prentice's research while affiliated with Fred Hutch Cancer Center and other places

Publications (634)

Article
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There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits m...
Article
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Background Genome-wide studies of gene–environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen recept...
Article
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Addressing systematic measurement errors in self-reported data is a critical challenge in association studies of dietary intake and chronic disease risk. The regression calibration method has been utilized for error correction when an objectively measured biomarker is available; however, biomarkers for only a few dietary components have been develo...
Article
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Colorectal cancer (CRC) risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment (G×E) interactions can provide biological insights into the effects of obesity on CRC risk. Here, we assessed potential genome-wide G×E interactions between body mass index (BMI) and common single nucleotide po...
Article
Background: A substantial observational literature relating specific fatty acid classes to chronic disease risk may be limited by its reliance on self-reported dietary data. Objectives: We aimed to develop biomarkers for saturated (SFA), monounsaturated (MFA) and polyunsaturated (PFA) fatty acid densities, and to study their associations with ca...
Article
Background: The Women's Health Initiative (WHI) randomized, controlled Dietary Modification (DM) trial of a low-fat dietary pattern suggested intervention benefits related to breast cancer, coronary heart disease (CHD), and diabetes. Here we use WHI observational data for the further insight into the chronic disease implications of adopting this t...
Article
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Obesity is caused by a prolonged positive energy balance1,2. Whether reduced energy expenditure stemming from reduced activity levels contributes is debated3,4. Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased ove...
Article
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Demographic and clinical factors influence the metabolome. The discovery and validation of disease biomarkers are often challenged by potential confounding effects from such factors. To address this challenge, we investigated the magnitude of the correlation between serum and urine metabolites and demographic and clinical parameters in a well-chara...
Article
Background: The aging process alters resting metabolic rate (RMR) but it still accounts for 50-70% of total energy needs. The rising proportion of older adults, especially those over 80 years of age, underpins the need for a simple, rapid method to estimate the energy needs of older adults. Objective: This research aimed to generate and validate...
Article
Background: The association of total energy expenditure with all-cause mortality is uncertain, as is the dependence of this association on age. Objective: To examine the association between total energy expenditure and all-cause mortality, and its age interaction, in a Women's Health Initiative (WHI) cohort of postmenopausal U.S. females (1992-p...
Preprint
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Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addre...
Article
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Circulating concentrations of metabolites (collectively called kynurenines) in the kynurenine pathway of tryptophan metabolism increase during inflammation, particularly in response to interferon-gamma (IFN-γ). Neopterin and the kynurenine/tryptophan ratio (KTR) are IFN-γ induced inflammatory markers, and together with C-reactive protein (CRP) and...
Article
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Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analy...
Article
Nutrition influences health throughout the life course. Good nutrition increases the probability of good pregnancy outcomes, proper childhood development, and healthy aging, and it lowers the probability of developing common diet-related chronic diseases, including obesity, cardiovascular disease, cancer, and type 2 diabetes. Despite the importance...
Article
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Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast c...
Article
Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lacks access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5604 people from the ages of 8 days to 96 years from 23 countries using...
Article
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In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a...
Article
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Importance: About 25% of all triple-negative breast cancers (TNBCs) and 10% to 20% of high-grade serous ovarian cancers (HGSOCs) harbor BRCA1 promoter methylation. While constitutional BRCA1 promoter methylation has been observed in normal tissues of some individuals, the potential role of normal tissue methylation as a risk factor for incident TN...
Article
Background Prior studies examined associations between Healthy Eating Index (HEI) and chronic disease risk based on self-reported diet without measurement error correction. Objectives Our objective was to test associations between biomarker-calibration of food frequency questionnaire (FFQ)-derived HEI-2010 with incident cardiovascular disease (CVD...
Article
The WHI (Women’s Health Initiative) enrolled 161,808 racially and ethnically diverse postmenopausal women, ages 50-79 years, from 1993 to 1998 at 40 clinical centers across the United States. In its clinical trial component, WHI evaluated 3 randomized interventions (menopausal hormone therapy; diet modification; and calcium/vitamin D supplementatio...
Article
Correction for systematic measurement error in self-reported data is an important challenge in association studies of dietary intake and chronic disease risk. The regression calibration method has been used for this purpose when an objectively measured biomarker is available. However, a big limitation of the regression calibration method is that bi...
Article
Full-text available
Lower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (-10 to +30°C) on TEE, basal (BEE) and acti...
Article
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There are several different topics that can be addressed with multivariate failure time regression data. Data analysis methods are needed that are suited to each such topic. Specifically, marginal hazard rate models are well suited to the analysis of exposures or treatments in relation to individual failure time outcomes, when failure time dependen...
Article
10509 Background: About 25% of all triple-negative breast cancer (TNBC) and 10–20% of high-grade serous ovarian cancers (HGSOC) harbor BRCA1 promoter methylation. While constitutional BRCA1 promoter methylation has been observed in normal tissues of some individuals, the potential role of normal tissue methylation as a risk factor for incident TNBC...
Article
Dietary intake biomarkers that can be written as actual intake, plus ‘error’ that is independent of actual intake and confounding factors can substitute for actual intake in disease association analyses. Also, such biomarkers can be used to develop calibration equations using self-reported diet and participant measures, and biomarker-calibrated int...
Article
Background: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. Methods: We conducted a genome-wide gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen-only, and combined estrogen-progestogen therapy with CRC risk, among 28,486...
Article
Background: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. Methods: Individual-level data was pooled from...
Article
Full-text available
Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 obse...
Article
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Background The associations of red and processed meat with chronic disease risk remains unsettled, in part because of measurement error in self-reported diet. Objectives To develop metabolomics-based biomarkers for red and processed meat, and to associate biomarker-calibrated meat intake with chronic disease risk among postmenopausal women. Desig...
Article
Background Studies of diet and chronic disease include a recent important focus on dietary patterns. Patterns are typically defined by listing dietary variables, and by totaling scores that reflect whether consumption is encouraged or discouraged for listed variables. However, precision may be improved by including total energy consumption among th...
Article
Background: Currently known associations between common genetic variants and colorectal cancer (CRC) explain less than half of its heritability of 25%. As alcohol consumption has a Jshape association with CRC risk, non-drinking and heavy drinking are both risk factors for CRC. Methods: Individual-level data was pooled from Colon Cancer Family Regis...
Article
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Background The association of social isolation or lack of social network ties in older adults is unknown. This knowledge gap is important since the risk of heart failure (HF) and social isolation increase with age. The study examines whether social isolation is associated with incident HF in older women, and examines depressive symptoms as a potent...
Article
Background Plasma phospholipid pentadecanoic acid (C15:0), heptadecanoic acid (C17:0), and trans-palmitoleic acid (trans-C16:1n-7) are correlates of dairy fat intake. However, their relative concentrations may be influenced by other endogenous factors, such as liver fat content, and their validity as biomarkers of dairy fat intake has yet to be est...
Article
We recently presented associations of biomarker-calibrated protein, protein density, carbohydrate, and carbohydrate density with the incidence of cardiovascular diseases, cancers, and diabetes in Women’s Health Initiative cohorts (1993 to present, at 40 US clinical centers) of postmenopausal women. The biomarkers relied on serum and urine metabolom...
Article
Obesity and obesity-related metabolic disorders, such as diabetes and chronic inflammation, have been positively associated both with postmenopausal breast cancer and with resting energy expenditure (REE). However, there is limited epidemiologic evidence on the associations between REE and risk of postmenopausal breast cancer. We used multivariable...
Article
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Low total energy expenditure (TEE, MJ/d) has been a hypothesized risk factor for weight gain, but repeatability of TEE, a critical variable in longitudinal studies of energy balance, is understudied. We examine repeated doubly labeled water (DLW) measurements of TEE in 348 adults and 47 children from the IAEA DLW Database (mean ± SD time interval:...
Article
Background We recently developed protein and carbohydrate intake biomarkers using metabolomics profiles in serum and urine, and used them to correct self-reported dietary data for measurement error. Biomarker-calibrated carbohydrate density was inversely associated with chronic disease risk, while protein density associations were mixed. Objective...
Article
Full-text available
Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast ca...
Article
Background Dietary biomarkers measured in biospecimens can play an important role in correcting for random and systematic measurement error in self-reported nutrient intake when assessing diet-disease associations. To date, high quality biomarkers for calibrating self-reported dietary intake have only been developed for a few nutrients. Objective...
Article
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PurposeObjective biomarkers of dietary exposure are needed to establish reliable diet-disease associations. Unfortunately, robust biomarkers of macronutrient intakes are scarce. We aimed to assess the utility of serum, 24-h urine and spot urine high-dimensional metabolites for the development of biomarkers of daily intake of total energy, protein,...
Article
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Background Assessing estimated sodium (Na) and potassium (K) intakes derived from 24-h urinary excretions versus a spot urine sample if comparable could reduce participant burden in epidemiologic and clinical studies. Objectives In a two-week controlled feeding study, Na and K excretion from a 24-h urine collection were compared with a first void...
Article
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Background: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass. Objectives: A study is presented of the association between FFM and physical activity in relation to age. Methods: In a cross-sectional study, FFM was analyzed in relation t...
Article
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BACKGROUND: Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. METHODS: We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on...
Article
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Abstract Background Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods We performed genome-wide association analyses within 15 subgroups of breast cancer patients ba...
Article
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A lifetime of change Measurements of total and basal energy in a large cohort of subjects at ages spanning from before birth to old age document distinct changes that occur during a human lifetime. Pontzer et al . report that energy expenditure (adjusted for weight) in neonates was like that of adults but increased substantially in the first year o...
Article
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Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.1, 2, 3 This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-te...
Article
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Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We ana...
Conference Paper
Background and objective Genetic predisposition and menopausal hormone therapy (MHT) are established risk and preventive factors for colorectal cancer (CRC), respectively. We aimed to evaluate the joint associations of a polygenic risk score (PRS) and MHT on CRC risk for informing CRC prevention. Methods We used data from 28,486 postmenopausal wome...
Conference Paper
Colorectal cancer (CRC) is a heterogenous disease that develops through somatic mutations in driver genes, leading to activation of diverse neoplastic pathways. To systematically examine if somatically mutated genes and pathways impact survival, we sequenced tumor and normal DNA samples for 4,512 CRC cases using a targeted panel. We performed Cox r...
Article
Dietary guidance emphasizes healthy dietary patterns, but supporting evidence comes from measurement-error prone self-reported diet. We explored whether nutritional biomarkers from the Women’s Health Initiative Nutrition and Physical Activity Assessment Study Feeding Study (n=153; 2010-2014) and the WHI-NPAAS Observational Study (NPAAS-OS; n=450; 2...
Preprint
Full-text available
Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785...
Preprint
Full-text available
Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785...
Article
Background /Objective: Insomnia is common in older women and is associated with higher cardiovascular disease risk (CVD). Nonbenzodiazepine GABA agonists (Z-drugs) are the most commonly prescribed sleep aids. The study objective was to determine whether the use of Z-drugs is associated with the risk of developing CVD and mortality in older women wi...
Article
Background Knowledge about macronutrient intake and chronic disease risk has been limited by the absence of objective macronutrient measures. Recently, we proposed novel biomarkers for protein, protein density, carbohydrate, and carbohydrate density, using established biomarkers and serum and urine metabolomics profiles in a human feeding study. O...
Article
Full-text available
The dietary modification (DM) clinical trial, within the Women's Health Initiative (WHI), studied a low-fat dietary pattern intervention that included guidance to increase vegetables, fruit, and grains. This study was motivated in part from uncertainty about the reliability of observational studies examining the association between dietary fat and...
Article
Background Obesity is associated with an increased risk of heart failure (HF); however, how metabolic weight groups relate to HF risk, especially in postmenopausal women, has not been demonstrated. Methods We included 19 412 postmenopausal women ages 50 to 79 without cardiovascular disease from the Women’s Health Initiative. Normal weight was defi...
Article
Full-text available
Objective An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk fa...
Article
Full-text available
The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The...
Article
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Background Prior studies of dietary protein intake and breast cancer have been mixed with previous studies limited by dietary self-report measurement error. Methods Biomarker-calibrated total protein intake and estimated vegetable protein and animal protein intake were determined from baseline food frequency questionnaires (FFQ) in 100,024 Women’s...
Article
The health benefits and risks of menopausal hormone therapy among women aged 50-59 years are examined in the Women's Health Initiative randomized, placebo-controlled trials using long-term follow-up data and a parsimonious statistical model that leverages data from older participants to increase precision. These trials enrolled 27,347 healthy post-...
Article
The identification of valid surrogate markers of disease or disease progression has the potential to decrease the length and costs of future studies. Most available methods that assess the value of a surrogate marker ignore the fact that surrogates are often measured with error. Failing to adjust for measurement error can erroneously identify a use...
Article
Importance The influence of menopausal hormone therapy on breast cancer remains unsettled with discordant findings from observational studies and randomized clinical trials. Objective To assess the association of prior randomized use of estrogen plus progestin or prior randomized use of estrogen alone with breast cancer incidence and mortality in...
Article
Background: The carbon isotope ratio (CIR) is a proposed biomarker for added sugar (AS) intake in the United States; however, because the CIR is also associated with meat intake in most populations the need for specificity remains. The CIR of amino acids (AAs) has the potential to differentiate sugars from meat intakes, because essential AAs must...
Article
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Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1–3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel m...
Preprint
Full-text available
Objective An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk fa...
Article
Full-text available
We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72,284 cases and 80,354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression, and a newly developed case-only method, fo...
Article
Dual outcome intention-to-treat hazard rate analyses have potential to complement single outcome analyses for the evaluation of treatments or exposures in relation to multivariate time-to-response outcomes. Here we consider pairs formed from important clinical outcomes for further insight into menopausal hormone therapy influences on chronic diseas...
Article
After reports from the Women's Health Initiative randomized trial evaluating estrogen plus progestin, there was a sudden, substantial, and sustained decrease in all categories of menopausal hormone therapy, and the first reduction in age‐adjusted breast cancer incidence in more than 20 years was seen in 2003‐2004 among US women 50 years of age or o...
Article
Background: We recently presented associations between serum-based biomarkers of carotenoid and tocopherol intake and chronic disease risk in a Women's Health Initiative (WHI) Measurement Precision subcohort (n = 5488). Questions remain as to whether self-reported dietary data can usefully augment such biomarkers or can be calibrated using biomark...
Conference Paper
Background: Breast cancer outcomes from the Women’s Health Initiative (WHI) Estrogen plus Progestin and Estrogen-alone trials have been reported but issues remain regarding long- term, post-intervention influence on breast cancer incidence and the influence of time from menopause to hormone therapy initiation (gap time) on breast cancer findings. D...
Article
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Background: Women without cardiovascular disease (CVD) or hypertension at baseline assigned to intervention in the Women's Health Initiative Dietary Modification (DM) trial experienced 30% lower risk of coronary heart disease (CHD), whereas results in women with hypertension or prior CVD could have been confounded by postrandomization use of stati...
Article
PURPOSE Observational studies of dietary fat intake and breast cancer have reported inconsistent findings. This topic was addressed in additional analyses of the Women’s Health Initiative (WHI) Dietary Modification (DM) clinical trial that evaluated a low-fat dietary pattern influence on breast cancer incidence. METHODS In the WHI DM trial, 48,835...