Publications by authors named "Lesley F Tinker"

134 Publications

Smoking methylation marks for prediction of urothelial cancer risk.

Cancer Epidemiol Biomarkers Prev 2021 Sep 14. Epub 2021 Sep 14.

Precision Medicine, School of Clinical Sciences at Monash Healh, Monash University

Background: Self-reported information may not accurately capture smoking exposure. We aimed to evaluate whether smoking-associated DNA methylation markers improve urothelial cell carcinoma (UCC) risk prediction.

Methods: Conditional logistic regression was used to assess associations between blood-based methylation and UCC risk using two matched case-control samples, N=404 pairs from the Melbourne Collaborative Cohort Study (MCCS) and N=440 pairs from the Women's Health Initiative (WHI) cohort, respectively. Results were pooled using fixed-effects meta-analysis. We developed methylation-based predictors of UCC and evaluated their prediction accuracy on two replication datasets using the area under the curve (AUC).

Results: The meta-analysis identified associations (P<4.7×10-5) for 29 of 1,061 smoking-associated methylation sites, but these were substantially attenuated after adjustment for self-reported smoking. Nominally significant associations (P<0.05) were found for 387 (36%) and 86 (8%) of smoking-associated markers without/with adjustment for self-reported smoking, respectively, with same direction of association as with smoking for 387 (100%) and 79 (92%) markers. A Lasso-based predictor was associated with UCC risk in one replication dataset in MCCS (N=134, odds ratio per SD [OR]=1.37, 95%CI=1.00-1.90) after confounder adjustment; AUC=0.66, compared with AUC=0.64 without methylation information. Limited evidence of replication was found in the second testing dataset in WHI (N=440, OR=1.09, 95%CI=0.91-1.30).

Conclusions: Combination of smoking-associated methylation marks may provide some improvement to UCC risk prediction. Our findings need further evaluation using larger datasets.

Impact: DNA methylation may be associated with UCC risk beyond traditional smoking assessment and could contribute to some improvements in stratification of UCC risk in the general population.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0313DOI Listing
September 2021

An approximate quasi-likelihood approach for error-prone failure time outcomes and exposures.

Stat Med 2021 Oct 22;40(23):5006-5024. Epub 2021 Jun 22.

Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Measurement error arises commonly in clinical research settings that rely on data from electronic health records or large observational cohorts. In particular, self-reported outcomes are typical in cohort studies for chronic diseases such as diabetes in order to avoid the burden of expensive diagnostic tests. Dietary intake, which is also commonly collected by self-report and subject to measurement error, is a major factor linked to diabetes and other chronic diseases. These errors can bias exposure-disease associations that ultimately can mislead clinical decision-making. We have extended an existing semiparametric likelihood-based method for handling error-prone, discrete failure time outcomes to also address covariate error. We conduct an extensive numerical study to compare the proposed method to the naive approach that ignores measurement error in terms of bias and efficiency in the estimation of the regression parameter of interest. In all settings considered, the proposed method showed minimal bias and maintained coverage probability, thus outperforming the naive analysis which showed extreme bias and low coverage. This method is applied to data from the Women's Health Initiative to assess the association between energy and protein intake and the risk of incident diabetes mellitus. Our results show that correcting for errors in both the self-reported outcome and dietary exposures leads to considerably different hazard ratio estimates than those from analyses that ignore measurement error, which demonstrates the importance of correcting for both outcome and covariate error.
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http://dx.doi.org/10.1002/sim.9108DOI Listing
October 2021

Novel application of nutritional biomarkers from a controlled feeding study and observational study toward dietary pattern characterization in postmenopausal women.

Am J Epidemiol 2021 Jun 18. Epub 2021 Jun 18.

Division of Public Health Sciences. Fred Hutchinson Cancer Research Center, Seattle, WA.

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; 2006-2009) could identify biomarker signatures of dietary patterns for development of corresponding regression calibration equations to help mitigate measurement error. Fasting blood was assayed for a specific panel of vitamins, carotenoids and phospholipid fatty acids; 24-hour urine was assayed for nitrogen, sodium and potassium. NPAAS Feeding Study intake records were used to calculate participant Healthy Eating Index-2010 (HEI-2010), Alternative Healthy Eating Index-2010, Alternative Mediterranean Diet (aMED) and Dietary Approaches to Stop Hypertension scores. Scores were regressed on blood and urine nutritional measures for discovery of dietary pattern biomarkers using a cross-validated model R2> 36% criterion (stage one). Next, stepwise models (p<0.10 for entry, removal) using NPAAS-OS regressed stage one dietary pattern biomarkers on NPAAS-OS self-reported dietary pattern scores using food frequency questionnaire, four-day food record and 24-hour recall (stage two). HEI-2010 and aMED analyses achieved cross-validated R2>36% in stage one; while Alternative Healthy Eating Index-2010 and Dietary Approaches to Stop Hypertension analyses did not. R2 for HEI-2010 stage two calibration equations were: food frequency questionnaire: 63.5%, four-day food record: 83.1% and 24-hour recall: 77.8%; while stage 2 aMED R2 were 34.9-46.8%. Dietary pattern biomarkers have potential for calibrating self-report to enhance diet-disease association studies.
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http://dx.doi.org/10.1093/aje/kwab171DOI Listing
June 2021

Change to a Higher Carbohydrate Diet and Energy Expenditure among Postmenopausal Women.

J Nutr 2021 Jun;151(6):1673-1674

Department of Medicine, Georgetown University Medical Center, and MedStar Health Research Institute, Hyattsville MD, USA.

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http://dx.doi.org/10.1093/jn/nxab095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169807PMC
June 2021

Association of Macular Thickness With Age and Age-Related Macular Degeneration in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2), An Ancillary Study of the Women's Health Initiative.

Transl Vis Sci Technol 2021 02;10(2):39

Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Purpose: To evaluate the relationship of retinal layer thickness with age and age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study 2.

Methods: Total retinal thickness within the macular area, and individual layer thickness was determined for CAREDS2 participants (n = 906 eyes, 473 women) from the Women's Health Initiative using Heidelberg optical coherence tomography (OCT). Mean measurements within the OCT grid were compared across age tertiles (69-78, 78-83, and 83-101 years) and AMD outcomes.

Results: Mean retinal thickness in the central circle, inner ring, and outer ring were 277 ± 34 µm, 326 ± 20 µm, and 282 ± 15 µm, respectively. Thickness did not vary by age in the central circle, but decreased with age in the inner and outer circles (P ≤ 0.004). Specifically, ganglion cell (GCL), inner plexiform, and outer nuclear (ONL) layer thickness decreased with age (P ≤ 0.003). Age-adjusted retinal thickness in all three circles did not vary by AMD outcomes (486 without AMD and 413 with AMD). However, individual layers showed changes with GCL and photoreceptor thinning and retinal pigment epithelial thicknening in eyes with late AMD. After controlling for age and AMD, higher ONL thickness was associated with better visual acuity.

Conclusions: In this cohort of older women, a decrease in perifoveal thickness was associated with increasing age, particularly in the inner retinal layers. Variabilty in thickness in AMD eyes was primarily due to outer retinal layers. Among all retinal layers, the ONL plays an important role in preserving visual acuity.

Translational Relevance: The study provides a deeper understanding of age related changes to the retinal layers and their effect on visual loss.
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http://dx.doi.org/10.1167/tvst.10.2.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910637PMC
February 2021

Evaluation of potential metabolomic-based biomarkers of protein, carbohydrate and fat intakes using a controlled feeding study.

Eur J Nutr 2021 May 15. Epub 2021 May 15.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Purpose: Objective 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, carbohydrate and fat, and the percent of energy from these macronutrients (%E).

Methods: A 2-week controlled feeding study mimicking the participants' habitual diets was conducted among 153 postmenopausal women from the Women's Health Initiative (WHI). Fasting serum metabolomic profiles were analyzed using a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for aqueous metabolites and a direct-injection-based quantitative lipidomics platform. Urinary metabolites were analyzed using H nuclear magnetic resonance (NMR) spectroscopy at 800 MHz and by untargeted gas chromatography-mass spectrometry (GC-MS). Variable selection was performed to build prediction models for each dietary variable.

Results: The highest cross-validated multiple correlation coefficients (CV-R) for protein intake (%E) and carbohydrate intake (%E) using metabolites only were 36.3 and 37.1%, respectively. With the addition of established dietary biomarkers (doubly labeled water for energy and urinary nitrogen for protein), the CV-R reached 55.5% for energy (kcal/d), 52.0 and 45.0% for protein (g/d, %E), 55.9 and 37.0% for carbohydrate (g/d, %E).

Conclusion: Selected panels of serum and urine metabolites, without the inclusion of doubly labeled water and urinary nitrogen biomarkers, give a reliable and robust prediction of daily intake of energy from protein and carbohydrate.
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http://dx.doi.org/10.1007/s00394-021-02577-1DOI Listing
May 2021

Biomarker-Calibrated Macronutrient Intake and Chronic Disease Risk among Postmenopausal Women.

J Nutr 2021 Aug;151(8):2330-2341

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

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.

Objectives: We aimed to use these biomarkers to develop calibration equations for macronutrient variables using dietary self-reports and personal characteristics and to study the association between biomarker-calibrated intake estimates and cardiovascular disease, cancer, and diabetes risk in Women's Health Initiative (WHI) cohorts.

Methods: Prospective disease association analyses are based on WHI cohorts of postmenopausal US women aged 50-79 y when enrolled at 40 US clinical centers (n = 81,954). We used biomarker intake values in a WHI nutritional biomarker study (n = 436) to develop calibration equations for each macronutrient variable, leading to calibrated macronutrient intake estimates throughout WHI cohorts. We then examined the association of these intakes with chronic disease incidence over a 20-y (median) follow-up period using HR regression methods.

Results: In analyses that included doubly labeled water-calibrated total energy, HRs for cardiovascular diseases and cancers were mostly unrelated to calibrated protein density. However, many were inversely related to carbohydrate density, with HRs (95% CIs) for a 20% increment in carbohydrate density of 0.81 (0.69, 0.95) and 0.83 (0.74, 0.93), respectively, for primary outcomes of coronary heart disease and breast cancer, as well as 0.74 (0.60, 0.91) and 0.87 (0.81, 0.93) for secondary outcomes of heart failure and total invasive cancer. Corresponding HRs (95% CIs) for type 2 diabetes incidence in relation to protein density and carbohydrate density were 1.17 (1.09, 1.75) and 0.73 (0.66, 0.80), respectively.

Conclusions: At specific energy intake, a diet high in carbohydrate density is associated with substantially reduced risk of major chronic diseases in a population of US postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00000611.
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http://dx.doi.org/10.1093/jn/nxab091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349120PMC
August 2021

Nutritional epidemiology and the Women's Health Initiative: a review.

Am J Clin Nutr 2021 05;113(5):1083-1092

Lundquist Institute for Innovative Biomedical Research at Harbor-UCLA Medical Center, Torrance, CA, USA.

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 chronic disease risk by using self-reported dietary data. In addition to this large trial, which had breast and colorectal cancer as its primary outcomes, a substantial biomarker research effort was initiated midway in the WHI program to contribute to nutritional epidemiology research more broadly. Here we review and update findings from the DM trial and from the WHI nutritional biomarker studies and examine implications for future nutritional epidemiology research. The WHI included the randomized controlled DM trial (n = 48,835) and a prospective cohort observational (OS) study (n = 93,676), both among postmenopausal US women, aged 50-79 y when enrolled during 1993-1998. Also reviewed is a nutrition and physical activity assessment study in a subset of 450 OS participants (2007-2009) and a related controlled feeding study among 153 WHI participants (2010-2014). Long-term follow-up in the DM trial provides evidence for intervention-related reductions in breast cancer mortality, diabetes requiring insulin, and coronary artery disease in the subset of normotensive healthy women, without observed adverse effects or changes in all-cause mortality. Studies of intake biomarkers, and of biomarker-calibrated intake, suggest important associations of total energy intake and macronutrient dietary composition with the risk for major chronic diseases among postmenopausal women. Collectively these studies argue for a nutrition epidemiology research agenda that includes major efforts in nutritional biomarker development, and in the application of biomarkers combined with self-reported dietary data in disease association analyses. We expect such efforts to yield novel disease association findings and to inform disease prevention approaches for potential testing in dietary intervention trials. This trial was registered at clinicaltrials.gov as NCT00000611.
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http://dx.doi.org/10.1093/ajcn/nqab091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120331PMC
May 2021

Eggs, dietary cholesterol, choline, betaine, and diabetes risk in the Women's Health Initiative: a prospective analysis.

Am J Clin Nutr 2021 07;114(1):368-377

Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, CA, USA.

Background: Epidemiological studies have been inconsistent regarding the relations between diabetes risk and the consumption of eggs and nutrients in eggs, such as choline, betaine, and cholesterol. There have been few studies among elderly women.

Objectives: The objective of this study was to examine associations between consumption of eggs, cholesterol, choline, and betaine and the risk of diabetes among elderly US women.

Methods: Multivariable Cox regression was used with data from the prospective Women's Health Initiative. Population attributable risks were calculated. Consumption of eggs alone (not mixed in foods) and nutrients were assessed with an FFQ. Diabetes incidence was defined as the first incidence of self-reported diabetes treated with oral diabetes medication or insulin injections.

Results: There were 46,263 women at follow-up baseline. During 13.3 y and 592,984 person-years of follow-up, there were 5480 incident diabetes cases. Higher egg, cholesterol, and choline consumption were each significantly associated with increases in diabetes risk. The associations for eggs and choline were not significant after adjustment for cholesterol consumption. The association for eggs was attenuated after adjustment for non-egg cholesterol consumption, with 1 significant HR in the top consumption quintile (≥3 eggs/wk) of 1.15 (95% CI: 1.05, 1.27; P for linear trend = 0.0001). The population attributable risks for obesity, overweight, consumption of ≥3 eggs/wk, inadequate exercise, and poor diet were 25.0 (95% CI: 22.3, 27.6), 12.8 (95% CI: 11.1, 14.5), 4.2 (95% CI: 2.3, 6.1), 3.5 (95% CI: 1.2, 5.8), and 3.1 (95% CI: 0.5, 5.7), respectively.

Conclusions: As egg consumption increased to ≥3 eggs/wk, there was a steady increase in diabetes risk that may have been due to the cholesterol in the eggs. The population attributable risk for ≥3 eggs/wk was far lower than that for being obese or overweight.
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http://dx.doi.org/10.1093/ajcn/nqab036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246612PMC
July 2021

Dietary Patterns of Insulinemia, Inflammation and Glycemia, and Pancreatic Cancer Risk: Findings from the Women's Health Initiative.

Cancer Epidemiol Biomarkers Prev 2021 06 7;30(6):1229-1240. Epub 2021 Apr 7.

Interdisciplinary Ph.D. Program in Nutrition, The Ohio State University, Columbus, Ohio.

Background: Pancreatic cancer risk is increasing in countries with high consumption of Western dietary patterns and rising obesity rates. We examined the hypothesis that specific dietary patterns reflecting hyperinsulinemia (empirical dietary index for hyperinsulinemia; EDIH), systemic inflammation (empirical dietary inflammatory pattern; EDIP), and postprandial glycemia [glycemic index (GI); glycemic load (GL)] are associated with pancreatic cancer risk, including the potential modifying role of type 2 diabetes (T2D) and body mass index (BMI).

Methods: We calculated dietary scores from baseline (1993-1998) food frequency questionnaires among 129,241 women, 50-79 years-old in the Women's Health Initiative. We used multivariable-adjusted Cox regression to estimate HRs and 95% confidence intervals (95% CI) for pancreatic cancer risk.

Results: During a median 19.9 years of follow-up, 850 pancreatic cancer cases were diagnosed. We observed no association between dietary scores and pancreatic cancer risk overall. However, risk was elevated among participants with longstanding T2D (present >3 years before pancreatic cancer diagnosis) for EDIH. For each 1 SD increment in dietary score, the HRs (95% CIs) were: EDIH, 1.33 (1.06-1.66); EDIP, 1.26 (0.98-1.63); GI, 1.26 (0.96-1.67); and GL, 1.23 (0.96-1.57); although interactions were not significant (all >0.05). Separately, we observed inverse associations between GI [0.86 (0.76-0.96), = 0.0068] and GL [0.83 (0.73-0.93), = 0.0075], with pancreatic cancer risk among normal-weight women.

Conclusions: We observed no overall association between the dietary patterns evaluated and pancreatic cancer risk, although women with T2D appeared to have greater cancer risk.

Impact: The elevated risk for hyperinsulinemic diets among women with longstanding T2D and the inverse association among normal-weight women warrant further examination.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172436PMC
June 2021

Prediagnostic Antibody Responses to Proteins Are Not Associated with Risk of Colorectal Cancer in a Large U.S. Consortium.

Cancer Epidemiol Biomarkers Prev 2021 06 18;30(6):1279-1282. Epub 2021 Mar 18.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Background: The association between prediagnostic antibody responses to () and subsequent risk of colorectal cancer is not established.

Methods: We conducted a nested case-control study of 8,126 participants in a consortium of 10 prospective cohorts in the United States.

Results: Higher seroprevalence of any antibody was observed among non-White participants (51.1%) compared with White participants (31.2%). We did not find any statistically significant association between seropositivity to any of the eight proteins and colorectal cancer risk.

Conclusions: Prediagnostic antibody responses to proteins were not associated with the risk of colorectal cancer.

Impact: Future studies may consider a more specific detection of the immunoglobulin isotypes or focus on examining in stool or tissue samples.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172443PMC
June 2021

Women's Health Initiative Strong and Healthy Pragmatic Physical Activity Intervention Trial for Cardiovascular Disease Prevention: Design and Baseline Characteristics.

J Gerontol A Biol Sci Med Sci 2021 03;76(4):725-734

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Background: National guidelines promote physical activity to prevent cardiovascular disease (CVD), yet no randomized controlled trial has tested whether physical activity reduces CVD.

Methods: The Women's Health Initiative (WHI) Strong and Healthy (WHISH) pragmatic trial used a randomized consent design to assign women for whom cardiovascular outcomes were available through WHI data collection (N = 18 985) or linkage to the Centers for Medicare and Medicaid Services (N30 346), to a physical activity intervention or "usual activity" comparison, stratified by ages 68-99 years (in tertiles), U.S. geographic region, and outcomes data source. Women assigned to the intervention could "opt out" after receiving initial physical activity materials. Intervention materials applied evidence-based behavioral science principles to promote current national recommendations for older Americans. The intervention was adapted to participant input regarding preferences, resources, barriers, and motivational drivers and was targeted for 3 categories of women at lower, middle, or higher levels of self-reported physical functioning and physical activity. Physical activity was assessed in both arms through annual questionnaires. The primary outcome is major cardiovascular events, specifically myocardial infarction, stroke, or CVD death; primary safety outcomes are hip fracture and non-CVD death. The trial is monitored annually by an independent Data Safety and Monitoring Board. Final analyses will be based on intention to treat in all randomized participants, regardless of intervention engagement.

Results: The 49 331 randomized participants had a mean baseline age of 79.7 years; 84.3% were White, 9.2% Black, 3.3% Hispanic, 1.9% Asian/Pacific Islander, 0.3% Native American, and 1% were of unknown race/ethnicity. The mean baseline RAND-36 physical function score was 71.6 (± 25.2 SD). There were no differences between Intervention (N = 24 657) and Control (N = 24 674) at baseline for age, race/ethnicity, current smoking (2.5%), use of blood pressure or lipid-lowering medications, body mass index, physical function, physical activity, or prior CVD (10.1%).

Conclusion: The WHISH trial is rigorously testing whether a physical activity intervention reduces major CV events in a large, diverse cohort of older women. Clinical Trials Registration Number: NCT02425345.
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http://dx.doi.org/10.1093/gerona/glaa325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011700PMC
March 2021

Insulinemic and Inflammatory Dietary Patterns Show Enhanced Predictive Potential for Type 2 Diabetes Risk in Postmenopausal Women.

Diabetes Care 2021 03 8;44(3):707-714. Epub 2021 Jan 8.

Interdisciplinary PhD Program in Nutrition, The Ohio State University, Columbus, OH

Objective: The empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores assess the insulinemic and inflammatory potentials of habitual dietary patterns, irrespective of the macronutrient content, and are based on plasma insulin response or inflammatory biomarkers, respectively. The glycemic index (GI) and glycemic load (GL) assess postprandial glycemic potential based on dietary carbohydrate content. We tested the hypothesis that dietary patterns promoting hyperinsulinemia, chronic inflammation, or hyperglycemia may influence type 2 diabetes risk.

Research Design And Methods: We calculated dietary scores from baseline (1993-1998) food frequency questionnaires among 73,495 postmenopausal women in the Women's Health Initiative, followed through March 2019. We used multivariable-adjusted Cox regression to estimate hazard ratios (HRs) and 95% CIs for type 2 diabetes risk. We also estimated multivariable-adjusted absolute risk of type 2 diabetes.

Results: During a median 13.3 years of follow-up, 11,009 incident cases of type 2 diabetes were diagnosed. Participants consuming the most hyperinsulinemic or proinflammatory dietary patterns experienced greater risk of type 2 diabetes; HRs (95% CI) comparing highest to lowest dietary index quintiles were EDIH 1.49 (1.32-1.68; < 0.0001) and EDIP 1.45 (1.29-1.63; < 0.0001). The absolute excess incidence for the same comparison was 220 (EDIH) and 271 (EDIP) cases per 100,000 person-years. GI and GL were not associated with type 2 diabetes risk: GI 0.99 (0.88-1.12; = 0.46) and GL 1.01 (0.89-1.16; = 0.30).

Conclusions: Our findings in this diverse cohort of postmenopausal women suggest that lowering the insulinemic and inflammatory potentials of the diet may be more effective in preventing type 2 diabetes than focusing on glycemic foods.
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http://dx.doi.org/10.2337/dc20-2216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896263PMC
March 2021

Risk of metabolic syndrome and metabolic phenotypes in relation to biomarker-calibrated estimates of energy and protein intakes: an investigation from the Women's Health Initiative.

Am J Clin Nutr 2021 03;113(3):706-715

Biobehavioral Nursing and Health Informatics, University of Washington School of Nursing, Seattle, WA, USA.

Background: Metabolic syndrome (MetS) is associated with increased mortality independent of BMI, resulting in discordant metabolic phenotypes, such as metabolically healthy obese and metabolically unhealthy normal-weight individuals. Studies investigating dietary intake in MetS have reported mixed results, due in part to the limitations of self-reported measures.

Objectives: To investigate the role of biomarker-calibrated estimates of energy and protein in MetS and metabolic phenotypes.

Methods: Postmenopausal participants from the Women's Health Initiative (WHI) study who were free of MetS at baseline, had available data from FFQs at baseline, and had components of MetS at Year 3 (n = 3963) were included. Dietary energy and protein intakes were estimated using biomarker calibration methods. MetS was defined as 3 or more of the following: elevated serum triglycerides (≥150 mg/dL), low HDL cholesterol (<50 mg/dL), hypertension [systolic blood pressure (BP) ≥130 or diastolic BP ≥85 mmHg], elevated serum glucose (>100 mg/dL), and abdominal adiposity (waist circumference > 89 cm). Models were adjusted for age, WHI study component, race/ethnicity, education, income, smoking, recreational physical activity, disease history, and parity.

Results: For every 10% increment in total calibrated energy intake, women were at a 1.37-fold elevated risk of MetS (95% CI, 1.15-1.63); a 10% increment in calibrated total protein intake was associated with a 1.21-fold elevated risk of MetS (95% CI, 1.00-1.47). Specifically, animal protein intake was associated with MetS (OR, 1.08; 95% CI, 1.02-1.14), whereas vegetable protein intake was not (OR, 0.99; 95% CI, 0.95-1.03). No differences were seen when examining metabolic phenotypes.

Conclusions: We found that higher calibrated total energy, total protein, and total animal protein intakes were strongly associated with MetS. If replicated in clinical trials, these results will have implications for the promotion of energy and animal protein restrictions for the reduction of MetS risks.
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http://dx.doi.org/10.1093/ajcn/nqaa334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948844PMC
March 2021

Diet quality indices and risk of metabolic syndrome among postmenopausal women of Mexican ethnic descent in the Women's Health Initiative Observational Study.

Nutr Healthy Aging 2020 Nov 3;5(4):261-272. Epub 2020 Nov 3.

Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: The prevalence of metabolic syndrome is higher among minority populations, including individuals of Mexican ethnic descent. Whether alignment to healthy dietary patterns is associated with lower risk of metabolic syndrome in this population is largely unknown.

Objective: To prospectively evaluate the associations between diet quality scores and risk of metabolic syndrome and its components among postmenopausal women of Mexican ethnic descent.

Methods: A total of 334 women of Mexican ethnic descent who participated in the Women's Health Initiative (WHI) observational study without metabolic syndrome or diabetes at baseline (1993-1998) were included. Baseline diets were scored with the Alternate Mediterranean Diet (aMED), the Dietary Approaches to Stop Hypertension (DASH), the Healthy Eating Index (HEI-2010), the Mediterranean Diet Score (MDS), and the traditional Mexican Diet (MexD) score. Multivariable linear and logistic regression models were used to test the associations between baseline diet quality and risk of metabolic syndrome and its individual components at follow-up (2012-2013).

Results: Approximately 16% of women met the criteria for metabolic syndrome at follow-up. None of the diet quality indices were associated with risk of metabolic syndrome. However, higher vs lower DASH scores were associated with lower waist circumference (85.2 vs 88.0 cm) and glucose concentrations (90.0 vs 95.1 mg/dL), and higher HDL cholesterol (62.6 vs 59.0 mg/dL), while higher vs lower HEI-2010 scores were associated with lower waist circumference (83.9 vs 88.1 cm), triglycerides (103 vs 117 mg/dL) and glucose concentrations (89.5 vs 94.4 mg/dL), and higher HDL cholesterol levels (63.9 vs 58.5 mg/dL).

Conclusions: Diet quality was not associated with risk of metabolic syndrome in this population. However, the results suggest that alignment to DASH and HEI-2010 recommendations may be beneficial for reducing some individual components of metabolic syndrome among postmenopausal women of Mexican descent.
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http://dx.doi.org/10.3233/NHA-190076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745721PMC
November 2020

Alignment of Dietary Patterns With the Dietary Guidelines for Americans 2015-2020 and Risk of All-Cause and Cause-Specific Mortality in the Women's Health Initiative Observational Study.

Am J Epidemiol 2021 05;190(5):886-892

Poor diet quality is a leading risk factor for death in the United States. We examined the association between Healthy Eating Index-2015 (HEI-2015) scores and death from all causes, cardiovascular disease (CVD), cancer, Alzheimer disease, and dementia not otherwise specified (NOS) among postmenopausal women in the Women's Health Initiative Observational Study (1993-2017). This analysis included 59,388 participants who completed a food frequency questionnaire and were free of cancer, CVD, and diabetes at enrollment. Stratified Cox proportional hazards models were fit using person-years from enrollment as the underlying time metric. We estimated multivariable adjusted hazard ratios and 95% confidence intervals for risk of death associated with HEI-2015 quintiles, with higher scores reflecting more optimal diet quality. Over a median of 18.2 years, 9,679 total deaths 3,303 cancer deaths, 2,362 CVD deaths, and 488 deaths from Alzheimer disease and dementia NOS occurred. Compared with those with lower scores, women with higher HEI-2015 scores had an 18% lower risk of all-cause death and 21% lower risk of cancer death. HEI-2015 scores were not associated with death due to CVD, Alzheimer disease, and dementia NOS. Consuming a diet aligned with 2015-2020 US dietary guidelines may have beneficial impacts for preventing overall causes of death and death from cancer.
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http://dx.doi.org/10.1093/aje/kwaa268DOI Listing
May 2021

Mediation by differential DNA methylation of known associations between single nucleotide polymorphisms and bladder cancer risk.

BMC Med Genet 2020 11 19;21(1):228. Epub 2020 Nov 19.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: Though bladder cancer has been the subject of many well-powered genome-wide association studies, the mechanisms involving bladder-cancer-associated single nucleotide polymorphisms (SNPs) remain largely unknown. This study focuses on rs798766, rs401681, rs2294008, and rs8102137, which have been associated with bladder cancer and are also cis-acting methylation quantitative loci (mQTL).

Methods: Among 412 bladder cancer cases and 424 controls from the Women's Health Initiative (WHI), we assessed whether the effects of these SNPs on bladder cancer are mediated through proximal DNA methylation changes in pre-diagnostic blood at mQTL-associated CpG sites, which we refer to as natural indirect effects (NIEs). We used a multiple-mediator mediation model for each of the four mQTL adjusted for matching variables and potential confounders, including race/ethnicity, smoking status, and pack-years of smoking.

Results: While not statistically significant, our results suggest that substantial proportions of the modest effects of rs401681 (OR = 1.05, 95% confidence interval (CI) = 0.89 to 1.25; NIE percent = 98.5%) and rs2294008 (OR = 1.10, 95% CI = 0.90 to 1.33; NIE percent = 77.6%) on bladder cancer risk are mediated through differential DNA methylation at nearby mQTL-associated CpG sites. The suggestive results indicate that rs2294008 may affect bladder cancer risk through a set of genes in the lymphocyte antigen 6 family, which involves genes that bind to and modulate nicotinic acetylcholine receptors. There was no suggestive evidence supporting mediation for rs8102137 and rs798766.

Conclusions: Though larger studies are necessary, the methylation changes associated with rs401681 and rs2294008 at mQTL-associated CpG sites may be relevant for bladder carcinogenesis, and this study demonstrates how multi-omic data can be integrated to help understand the downstream effects of genetics variants.
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http://dx.doi.org/10.1186/s12881-020-01172-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678190PMC
November 2020

Authors Response.

J Acad Nutr Diet 2021 02 13;121(2):210-212. Epub 2020 Nov 13.

Family Medicine and Public Health, University of California, San Diego, La Jolla, CA.

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http://dx.doi.org/10.1016/j.jand.2020.10.015DOI Listing
February 2021

Association of Combined Sero-Positivity to and with Risk of Colorectal Cancer.

Microorganisms 2020 Oct 30;8(11). Epub 2020 Oct 30.

Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.

Previously, we found that risk of colorectal cancer (CRC) is increased in individuals with serum antibody response to both (HP) Vacuolating Cytotoxin (VacA) toxin or (SGG) pilus protein Gallo2178. In the present analysis, we tested the hypothesis that combined seropositivity to both antigens is a better indicator of CRC risk than seropositivity to single antigens. We used multiplex serologic assays to analyze pre-diagnostic serum for antibody responses from 4063 incident CRC cases and 4063 matched controls from 10 US cohorts. To examine whether combined SGG Gallo2178 and HP VacA sero-status was associated with CRC risk, we used conditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Compared to dual sero-negative individuals, there was no increased risk for individuals sero-positive to SGG Gallo2178 only (OR: 0.93; 95% CI: 0.66-1.31) or to HP VacA only (OR: 1.08; 95% CI: 0.98-1.19). However, dual sero-positive individuals had a >50% increased odds of developing CRC (OR: 1.54; 95% CI: 1.16-2.04), suggesting an interaction between antibody responses to these two pathogens and CRC risk (p = 0.06). In conclusion, this study suggests that dual sero-positivity to HP VacA and SGG Gallo2178 is an indicator of increased risk of CRC.
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http://dx.doi.org/10.3390/microorganisms8111698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693002PMC
October 2020

Walking Volume and Speed Are Inversely Associated With Incidence of Treated Hypertension in Postmenopausal Women.

Hypertension 2020 11 28;76(5):1435-1443. Epub 2020 Sep 28.

From the Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo-SUNY, NY (C.R.M., J.W.-W., K.M.H., M.J.L.).

Few studies have evaluated hypertension incidence in relation to walking, which is a common physical activity among adults. We examined the association between walking and hypertension incidence in 83 435 postmenopausal women who at baseline were aged 50 to 79 years, without known hypertension, heart failure, coronary heart disease, or stroke, and reported the ability to walk at least one block without assistance. Walking volume (metabolic equivalent hours per week) and speed (miles per hour) were assessed by questionnaire. Incident physician-diagnosed hypertension treated with medication was ascertained through annual questionnaires. During a mean 11-year follow-up, 38 230 hypertension cases were identified. After adjustment for covariates including nonwalking activities, a significant inverse association with hypertension was observed across categories of baseline walking volume (0 [referent], >0-3.5, 3.6-7.5, and >7.5 metabolic equivalent hours per week), hazard ratio: 1.00 (referent), 0.98, 0.95, 0.89; trend <0.001. Faster walking speeds (<2, 2-3, 3-4, and >4 miles per hour) also were associated with lower hypertension risk, hazard ratio: 1.00 (referent), 1.07, 0.95, 0.86, 0.79; trend <0.001. Further adjustment for walking duration (h/wk) had little impact on the association for walking speed (hazard ratio: 1.00 [referent], 1.08, 0.96, 0.86, 0.77; trend <0.001). Significant inverse associations for walking volume and speed persisted after additional control for baseline blood pressure. Results for time-varying walking were comparable to those for baseline exposures. This study showed that walking at guideline-recommended volumes (>7.5 metabolic equivalent hours per week) and at faster speeds (≥2 miles per hour) is associated with lower hypertension risk in postmenopausal women. Walking should be encouraged as part of hypertension prevention in older adults.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544673PMC
November 2020

Auto-antibodies to p53 and the Subsequent Development of Colorectal Cancer in a U.S. Prospective Cohort Consortium.

Cancer Epidemiol Biomarkers Prev 2020 12 24;29(12):2729-2734. Epub 2020 Sep 24.

Cancer Control and Population Sciences Program, Duke Cancer Institute, and Department of Population Health Sciences, Duke University, Durham, North Carolina.

Background: Auto-antibodies to tumor suppressor p53 are found in a subset of patients with colorectal cancer. A recent prospective study in the United States has reported a significant 1.8-fold increased odds for colorectal cancer development with prediagnostic seropositivity to p53. In this study, we sought to examine this association in a U.S. colorectal cancer cohort consortium to evaluate the potential utility of p53 auto-antibodies as an early biomarker for colorectal cancer.

Methods: Auto-antibodies to p53 were measured in prediagnostic blood samples of 3,702 incident colorectal cancer cases and 3,702 controls, matched by age, race, and sex, from 9 U.S. prospective cohorts. The association of seropositivity to p53 with colorectal cancer risk, overall and by time between blood draw and diagnosis, was determined by conditional logistic regression.

Results: Overall, 5% of controls and 7% of cases were seropositive to p53, resulting in a statistically significant 33% increased colorectal cancer risk [odds ratio (OR), 1.33; 95% confidence interval (CI), 1.09-1.61]. By follow-up time, the association was only significant with colorectal cancer diagnoses within 4 years after blood draw (OR, 2.27; 95% CI, 1.62-3.19), but not thereafter (OR, 0.97; 95% CI, 0.76-1.24).

Conclusions: In this large consortium of prospective cohorts, we found that prediagnostic seropositivity to tumor suppressor p53 was significantly associated with an over 2-fold increased odds of developing colorectal cancer within 4 years after blood draw.

Impact: Our finding suggests that p53 seropositivity may not be a useful predictor of long-term colorectal cancer risk; however, it might be considered as a marker to aid in the early diagnosis of colorectal cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710535PMC
December 2020

Racial Differences in CagA Sero-prevalence in a Consortium of Adult Cohorts in the United States.

Cancer Epidemiol Biomarkers Prev 2020 10 20;29(10):2084-2092. Epub 2020 Aug 20.

Cancer Control and Population Health Sciences Program, Duke Cancer Institute, Durham, North Carolina.

Background: Prevalence of () infection, the main risk factor for gastric cancer, has been decreasing in the United States; however, there remains a substantial racial disparity. Moreover, the time-trends for prevalence of CagA-positive infection, the most virulent form, are unknown in the U.S.

Population: We sought to assess prevalence of CagA-positive infection over time by race in the United States.

Methods: We utilized multiplex serology to quantify antibody responses to antigens in 4,476 participants across five cohorts that sampled adults from 1985 to 2009. Using log-binomial regression models, we calculated prevalence ratios and 95% confidence intervals for the association between -CagA sero-prevalence and birth year by race.

Results: African Americans were three times more likely to be -CagA sero-positive than Whites. After adjustment, -CagA sero-prevalence was lower with increasing birth year among Whites ( = 0.001), but remained stable for African Americans. When stratified by sex and education separately, the decline in -CagA sero-positivity among Whites remained only for females ( < 0.001) and was independent of educational attainment. Among African Americans, there was no difference by sex; furthermore, sero-prevalence increased with increasing birth year among those with a high school education or less ( = 0.006).

Conclusions: Among individuals in the United States born from the 1920s to 1960s, -CagA sero-prevalence has declined among Whites, but not among African Americans.

Impact: Our findings suggest a widening racial disparity in the prevalence of the most virulent form of , the main cause of gastric cancer.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584346PMC
October 2020

Associations of Number of Daily Eating Occasions with Type 2 Diabetes Risk in the Women's Health Initiative Dietary Modification Trial.

Curr Dev Nutr 2020 Aug 21;4(8):nzaa126. Epub 2020 Jul 21.

Canyon Ranch Center for Prevention & Health Promotion, Mel & Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA.

Background: Over 23 million Americans have type 2 diabetes (T2D). Eating habits such as breakfast consumption, time-restricted eating, and limiting daily eating occasions have been explored as behaviors for reducing T2D risk, but prior evidence is inconclusive.

Objectives: Our objectives were to examine associations between number of daily eating occasions and T2D risk in the Women's Health Initiative Dietary Modification Trial (WHI-DM) and whether associations vary by BMI, age, or race/ethnicity.

Methods: Participants were postmenopausal women in the WHI-DM who comprised a 4.6% subsample completing 24-h dietary recalls (24HRs) at years 3 and 6 as part of trial adherence activities ( = 2159). Numbers of eating occasions per day were obtained from the year 3 24HRs, and participants were grouped into approximate tertiles as 1-3 ( = 795), 4 ( = 713), and ≥5 ( = 651) daily eating occasions as the exposure. Incident diabetes was self-reported on semiannual questionnaires as the outcome.

Results: Approximately 15% (15.4%,  = 332) of the WHI-DM 24HR cohort reported incident diabetes at follow-up. Cox proportional hazards regression tested associations of eating occasions with T2D adjusted for neighborhood socioeconomic status, BMI, waist circumference, race/ethnicity, family history of T2D, recreational physical activity, Healthy Eating Index-2005, 24HR energy intake, and WHI-DM arm. Compared with women reporting 1-3 meals/d, those consuming 4 meals/d had a T2D HR = 1.38 (95% CI: 1.03, 1.84) without further increases in risk for ≥5 meals/d. In stratified analyses, associations for 4 meals/d compared with 1-3 meals/d were stronger in women with BMI <30.0 kg/m (HR = 1.55; 95% CI: 1.00, 2.39) and women aged ≥60 (HR = 1.61; 95% CI: 1.11, 2.33).

Conclusions: Four meals per day compared with 1-3 meals/d was associated with increased risk of T2D in postmenopausal women, but no dose-response effect was observed for additional eating occasions. Further studies are needed to understand eating occasions in relation to T2D risk.
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http://dx.doi.org/10.1093/cdn/nzaa126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431012PMC
August 2020

Barriers to eating are associated with poor physical function in older women.

Prev Med 2020 10 12;139:106234. Epub 2020 Aug 12.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4B402, Seattle, WA 98109-1024, USA. Electronic address:

Older adults have physical and social barriers to eating but whether this affects functional status is unknown. We examined associations between eating barriers and physical function in the Women's Health Initiative (WHI). In 2012-14, a subset of alive and participating women (n = 5910) completed an in-home examination including the Short Physical Performance Battery (SPPB) (grip strength, balance, timed walking speed, chair stand). WHI participants complete annual mailed questionnaires; the 2013-14 questionnaire included items on eating alone, eating < two meals/day, dentition problems affecting eating, physical difficulties with cooking/shopping and monetary resources for food. Linear regression tested associations of these eating barriers with SPPB, adjusting for BMI, age, race/ethnicity, and medical multimorbidities. Over half (56.8%) of participants were ≥ 75 years, 98.8% had a BMI ≥ 25.0 kg/m and 66% had multimorbidities. Eating barriers, excluding eating alone, were associated with significantly lower total (all p < .001) and component-specific, multivariate-adjusted SPPB scores (all p < .05). Compared to no barriers, eating < two meals/day (7.83 vs. 8.38, p < .0002), dentition problems (7.69 vs. 8.38, p < .0001), inability to shop/prepare meals (7.74 vs. 8.38, p < .0001) and insufficient resources (7.84 vs. 8.37 p < .001) were significantly associated with multivariate-adjusted mean SPPB score < 8. Models additionally adjusting for Healthy Eating Index-2010 had little influence on scores. As barriers increased, scores declined further for grip strength (16.10 kg for 4-5 barriers, p = .001), timed walk (0.58 m/s for 4-5 barriers, p = .001) and total SPPB (7.27 for 4-5 barriers, p < .0001). In conclusion, in this WHI subset, eating barriers were associated with poor SPPB scores.
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http://dx.doi.org/10.1016/j.ypmed.2020.106234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494579PMC
October 2020

Chocolate Candy and Incident Invasive Cancer Risk in the Women's Health Initiative: An Observational Prospective Analysis.

J Acad Nutr Diet 2021 02 4;121(2):314-326.e4. Epub 2020 Aug 4.

Background: Laboratory and animal studies suggest an inverse association between chocolate consumption and the risk of cancer. Epidemiological studies have yielded inconsistent evidence.

Objective: To assess the association of chocolate candy consumption with incident, invasive total, breast, colorectal, and lung cancers in a large cohort of postmenopausal American women.

Design: Prospective cohort study with a mean 14.8-year follow-up. Chocolate candy intake was assessed by food frequency questionnaire. Invasive cancer events were assessed by physician adjudication.

Participants/setting: The Women's Health Initiative Study enrolled 161,808 postmenopausal women at 40 clinical centers nationwide between 1993 and 1998. Of these women, 114,281 with plausible food frequency or biometric data and no missing data on chocolate candy exposure were selected for analysis.

Main Outcome Measures: Cancer risk in quartiles of chocolate candy consumption with the first quartile as referent.

Statistical Analyses: Multivariable Cox regression was used to calculate hazard ratios and 95% confidence intervals.

Results: There were 16,164 documented incident invasive cancers, representing an incidence rate of 17.0 per 100 participants and 12.3 per 1000 person years during follow-up among participants without any preexisting cancers or missing outcome data. There were no statistically significant associations for total invasive cancer (P-linear = .47, P-curvature = .14), or invasive breast cancer (P-linear = .77, P-curvature = .26). For colorectal cancer P-linear was .02, P-curvature was .03, and compared with women eating a 1 oz (28.4 g) chocolate candy serving <1 time per month, the hazard ratio for ≥1.5 times/wk was 1.18 (95% confidence interval: 1.04-1.35). This result may be attributable to the excess adiposity associated with frequent chocolate candy consumption.

Conclusions: In the Women's Health Initiative, there was no significant association between chocolate candy consumption and invasive total or breast cancer. There was a modest 18% higher risk of invasive colorectal cancer for women who ate chocolate candy at least 1.5 times/wk. These results require confirmation.
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http://dx.doi.org/10.1016/j.jand.2020.06.014DOI Listing
February 2021

The Carbon Isotope Ratios of Serum Amino Acids in Combination with Participant Characteristics can be Used to Estimate Added Sugar Intake in a Controlled Feeding Study of US Postmenopausal Women.

J Nutr 2020 10;150(10):2764-2771

Center for Alaska Native Health Research, Institute of Arctic Biology, Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, AK, USA.

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 derive from dietary protein whereas certain nonessential AAs can be synthesized from sugars.

Objectives: We tested whether serum CIR-AAs in combination with participant characteristics could meet a prespecified biomarker criterion for AS intake in the Nutrition and Physical Activity Assessment Study Feeding Study (NPAAS-FS) of the Women's Health Initiative, a population in which the whole-serum CIR was not associated with AS intake.

Methods: Postmenopausal women (n = 145) from Seattle, WA, were provided with individualized diets that approximated their habitual food intakes for 2 wk. Dietary intakes from consumed foods were characterized over the feeding period using the Nutrition Data System for Research. The CIR of 7 AAs-Ala, Gly, Val, Leu, Ile, Pro, and Phe-were measured in fasting serum collected at the end of the 2-wk feeding period, using gas chromatography-combustion isotope ratio mass spectrometry. Biomarker models were evaluated using regression R2 ≥ 0.36 as a major biomarker criterion, based on the benchmark R2 values of well-established recovery biomarkers in the NPAAS-FS.

Results: AS intake was associated with CIR-Ala (ρ = 0.32; P < 0.0001). A model of AS intake based on CIR-Ala, CIR-Gly, CIR-Ile, smoking, leisure physical activity, and body weight met the biomarker criterion (R2 = 0.37). Biomarker-estimated AS intake was not associated with meat or animal protein intake.

Conclusions: Results support serum CIR-AAs in combination with participant characteristics as potential biomarkers of AS intake in US populations, including those with low AS intake.The Women's Health Initiative is registered at clinicaltrials.gov (NCT00000611).
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http://dx.doi.org/10.1093/jn/nxaa195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549297PMC
October 2020

Risk of Breast Cancer Associated with Estrogen DNA Adduct Biomarker.

Cancer Epidemiol Biomarkers Prev 2020 10 22;29(10):2096-2099. Epub 2020 Jul 22.

Fred Hutch Cancer Research Center Public Health Sciences, Seattle, Washington.

Background: It is biologically plausible that genotoxic estrogens, namely estrogen DNA adducts (EDA), have a role in breast cancer development. Support comes from three prior studies that reported elevated concentrations of EDA relative to estrogen metabolites and conjugates (EDA:EMC) in women with breast cancer relative to control women.

Methods: In postmenopausal women in the Women's Health Initiative (WHI), EDA:EMC in 191 controls was compared with findings in 194 prediagnosis urine samples from breast cancer cases. EDA:EMC determinations were by mass spectrometry as previously described, and logistic regression was employed to estimate ORs.

Results: EDA:EMC did not differ in breast cancer cases compared with controls overall [0.93 (95% confidence interval, 0.71-1.23)], with a mean (SD) of 2.3 (0.8) and 2.4 (1.1) in cases and controls, respectively. Similarly, the ratio did not differ when examined by estrogen receptor or recency of biospecimen collection prior to breast cancer.

Conclusions: Despite the demonstrated genotoxic properties of certain catechol estrogens resulting in EDAs, this analysis did not provide evidence for an increased breast cancer risk in relation to an elevated EDA:EMC.

Impact: This analysis, conducted prospectively within postmenopausal women in the WHI study, suggests that a strong association between EDA:EMC and breast cancer could be ruled out, as this study was powered to detect an OR of 2.2 or greater.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541674PMC
October 2020

Dietary Intakes of Women's Health Initiative Long Life Study Participants Falls Short of the Dietary Reference Intakes.

J Acad Nutr Diet 2020 09 14;120(9):1530-1537. Epub 2020 Jul 14.

Background: Understanding how nutrient intake in older women compares with recommendations is important. The Academy of Nutrition and Dietetics position statement summarizes the nutrient needs of older adults (aged ≥60 years) based on a systematic review.

Objective: The objective of this study was to compare nutrient intake of Women's Health Initiative Long Life Study participants to the Dietary Reference Intakes for nutrients reviewed in the Academy of Nutrition and Dietetics position statement.

Design: The study is a cross-sectional analysis.

Participants/setting: Participants (n=7,875) were mailed the General Nutrition Assessment Food Frequency Questionnaire during 2012-2013, of whom 77% (n=6,095) completed it, and 5,732 were included in the analytic sample after exclusion for implausible energy intakes.

Main Outcome Measures: Mean intake of energy and protein, calcium, fiber, folate, potassium, sodium, vitamins B-12, D, E, and K were described overall and compared with recommendations.

Statistical Analyses Performed: Demographic and lifestyle characteristics were summarized using descriptive statistics. The proportion of participants meeting recommendations was computed.

Results: Mean age of completers was 79±7 years and 53.5% were non-Hispanic white, 30% were non-Hispanic black, and 16.5% were Hispanic/Latina. Only one-third of women consumed ≥21 g/day fiber, whereas fewer met the Recommended Dietary Allowance for calcium (18.6%), vitamin E (16.9%), and vitamin D (1.7%). Just more than half (56%) of participants met the Recommended Dietary Allowance for protein of 0.8 g/kg body weight/day, and just less than half (47.0%) met potassium guidelines.

Conclusions: These findings suggest older women within the Women's Health Initiative were generally not achieving recommended intake for several key nutrients highlighted by the Academy of Nutrition and Dietetics position statement. These findings underscore the need to identify effective approaches for improving the nutrient density of dietary intake in older women.
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http://dx.doi.org/10.1016/j.jand.2020.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566285PMC
September 2020

Short Physical Performance Battery and Incident Cardiovascular Events Among Older Women.

J Am Heart Assoc 2020 07 14;9(14):e016845. Epub 2020 Jul 14.

Department of Family Medicine and Public Health University of California San Diego La Jolla CA.

Background The Short Physical Performance Battery (SPPB) is an inexpensive, reliable, and easy-to-implement measure of lower-extremity physical function. Strong evidence links SPPB scores with all-cause mortality, but little is known about its relationship with incident cardiovascular disease (CVD). Methods and Results Women (n=5043, mean age=79±7) with no history of myocardial infarction or stroke completed 3 timed assessments-standing balance, strength (5 chair stands), and usual gait speed (4 m walk)-yielding an SPPB score from 0 (worst) to 12 (best). Women were followed for CVD events (myocardial infarction, stroke, or CVD death) up to 6 years. Hazard ratios were estimated for women with (0-3), (4-6), (7-9), and (10-12) SPPB scores using Cox proportional hazard models adjusted for demographic, behavioral, and health-related variables including objective measurements of physical activity, blood pressure, lipids, and glucose levels. Restricted cubic splines tested linearity of associations. With 361 CVD cases, crude incidence rates/1000 person-years were 41.0, 24.3, 16.1, and 8.6 for , , and SPPB categories, respectively. Corresponding fully adjusted hazard ratios (95% CIs) were 2.28 (1.50-3.48), 1.70 (1.23-2.36) 1.49 (1.12-1.98), and 1.00 (referent); -trend <0.001. The dose-response relationship was linear (linear <0.001; nonlinear >0.38). Conclusions Results suggest SPPB may provide a measure of cardiovascular health in older adults beyond that captured by traditional risk factors. Because of its high test-retest reliability and low administrative burden, the SPPB should be a routine part of office-based CVD risk assessment.
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http://dx.doi.org/10.1161/JAHA.120.016845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660732PMC
July 2020
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