Eating Pattern Response to a Low-Fat Diet Intervention and Cardiovascular Outcomes in Normotensive Women: The Women's Health Initiative.

BackgroundWomen 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 statins.ObjectivesIntervention participants reported various self-selected changes to achieve the 20% total fat goals. Reviewed are intervention compared with comparison group HRs for CHD, stroke, and total CVD in relation to specific dietary changes in normotensive participants.MethodsDietary change was assessed by comparing baseline with year 1 FFQ data in women (n = 10,371) without hypertension or CVD at baseline with intake of total fat above the median to minimize biases due to use of the FFQ in trial eligibility screening.ResultsIntervention participants self-reported compensating reduced energy intake from total fat by increasing carbohydrate and protein. Specifically they increased plant protein, with those in the upper quartile (increased total protein by ≥3.3% of energy) having a CHD HR of 0.39 (95% CI: 0.22, 0.71), compared with 0.92 (95% CI: 0.57, 1.48) for those in the lower quartile of change (decreased total protein ≥0.6% of energy), with P-trend of 0.04. CHD HR did not vary significantly with change in percentage energy from carbohydrate, and stroke HR did not vary significantly with any macronutrient changes. Scores reflecting adherence to recommended dietary patterns including the Dietary Approaches to Stop Hypertension Trial and the Healthy Eating Index showed favorable changes in the intervention group.ConclusionsIntervention group total fat reduction replaced with increased carbohydrate and some protein, especially plant-based protein, was related to lower CHD risk in normotensive women without CVD who reported high baseline total fat intake. This trial was registered at clinicaltrials.gov as NCT00000611. Link to the WHI trial protocol: https://www.whi.org/about/SitePages/Dietary%20Trial.aspx

Assessing Dietary Outcomes in Intervention Studies: Pitfalls, Strategies, and Research Needs.

To inform strategies to improve the dietary intakes of populations, robust evaluations of interventions are required. This paper is drawn from a workshop held at the International Society of Behavioral Nutrition and Physical Activity 2017 Annual Meeting, and highlights considerations and research priorities relevant to measuring dietary outcomes within intervention studies. Self-reported dietary data are typically relied upon in such studies, and it is recognized that these data are affected by random and systematic error. Additionally, differential error between intervention and comparison groups or pre- and post-intervention can be elicited by the intervention itself, for example, by creating greater awareness of eating or drinking occasions or the desire to appear compliant. Differential reporting can render the results of trials incorrect or inconclusive by leading to biased estimates and reduced statistical power. The development of strategies to address intervention-related biases requires developing a better understanding of the situations and population groups in which interventions are likely to elicit differential reporting and the extent of the bias. Also needed are efforts to expand the feasibility and applications of biomarkers to address intervention-related biases. In the meantime, researchers are encouraged to consider the potential for differential biases in dietary reporting in a given study, to choose tools carefully and take steps to minimize and/or measure factors such as social desirability biases that might contribute to differential reporting, and to consider the implications of differential reporting for study results

Concentrated sugars and incidence of prostate cancer in a prospective cohort

The association between consumption of added or concentrated sugars and prostate cancer risk is unclear. We examined the association between concentrated sugars in beverages and desserts and prostate cancer risk among 22 720 men in the usual-care arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, enrolled during 1993-2001. After a median follow-up of 9 years, 1996 men were diagnosed with prostate cancer. Cox proportional hazards regression models were used to estimate hazard ratios (HR) for prostate cancer risk and 95 % CI, adjusting for potential confounding factors. Increased consumption of sugars from sugar-sweetened beverages was associated with increased risk of prostate cancer for men in the highest quartile of sugar consumption (HR: 1·21; 95 % CI 1·06, 1·39), and there was a linear trend (P<0·01). There were no linear associations between prostate cancer risk and consumption of sugars from fruit juices or dessert foods. In conclusion, in this prospective substudy within the PLCO trial, consumption of sugars from sugar-sweetened beverages was associated with increased risk of prostate cancer among men receiving standard medical care. Our study suggests that limiting intake of sugars from beverages may be important in the prevention of prostate cancer

Variable selection with FDR control for noisy data -- an application to screening metabolites that are associated with breast and colorectal cancer

The rapidly expanding field of metabolomics presents an invaluable resource for understanding the associations between metabolites and various diseases. However, the high dimensionality, presence of missing values, and measurement errors associated with metabolomics data can present challenges in developing reliable and reproducible methodologies for disease association studies. Therefore, there is a compelling need to develop robust statistical methods that can navigate these complexities to achieve reliable and reproducible disease association studies. In this paper, we focus on developing such a methodology with an emphasis on controlling the False Discovery Rate during the screening of mutual metabolomic signals for multiple disease outcomes. We illustrate the versatility and performance of this procedure in a variety of scenarios, dealing with missing data and measurement errors. As a specific application of this novel methodology, we target two of the most prevalent cancers among US women: breast cancer and colorectal cancer. By applying our method to the Wome's Health Initiative data, we successfully identify metabolites that are associated with either or both of these cancers, demonstrating the practical utility and potential of our method in identifying consistent risk factors and understanding shared mechanisms between diseases

Use of complementary and alternative medicine and breast cancer survival in the Health, Eating, Activity, and Lifestyle Study

PURPOSE: Use of complementary and alternative medicine (CAM) is common among breast cancer patients, but less is known about whether CAM influences breast cancer survival. METHODS: Health Eating, Activity, and Lifestyle (HEAL) Study participants (n = 707) were diagnosed with stage I-IIIA breast cancer. Participants completed a 30-month post-diagnosis interview including questions on CAM use (natural products such as dietary and botanical supplements, alternative health practices, and alternative medical systems), weight, physical activity, and comorbidities. Outcomes were breast cancer-specific and total mortality, which were ascertained from the Surveillance Epidemiology and End Results registries in Western Washington, Los Angeles County, and New Mexico. Cox proportional hazards regression models were fit to data to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for mortality. Models were adjusted for potential confounding by sociodemographic, health, and cancer-related factors. RESULTS: Among 707 participants, 70 breast cancer-specific deaths and 149 total deaths were reported. 60.2 % of participants reported CAM use post-diagnosis. The most common CAM were natural products (51 %) including plant-based estrogenic supplements (42 %). Manipulative and body-based practices and alternative medical systems were used by 27 and 13 % of participants, respectively. No associations were observed between CAM use and breast cancer-specific (HR 1.04, 95 % CI 0.61-1.76) or total mortality (HR 0.91, 95 % CI 0.63-1.29). CONCLUSION: Complementary and alternative medicine use was not associated with breast cancer-specific mortality or total mortality. Randomized controlled trials may be needed to definitively test whether there is harm or benefit from the types of CAM assessed in HEAL in relation to mortality outcomes in breast cancer survivors

A meta-analysis of individual participant data reveals an association between circulating levels of IGF-I and prostate cancer risk

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. Aftermutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development.</p

Risk factors for self-reported arm lymphedema among female breast cancer survivors: a prospective cohort study

INTRODUCTION: Lymphedema is a potentially debilitating condition that occurs among breast cancer survivors. This study examines the incidence of self-reported lymphedema, timing of lymphedema onset, and associations between sociodemographic, clinical and lifestyle factors and lymphedema risk across racial-ethnic groups using data from a multicenter, multiethnic prospective cohort study of breast cancer survivors, the Health, Eating, Activity and Lifestyle Study. METHODS: A total of 666 women diagnosed with breast cancer staged as in situ, localized or regional disease at ages 35 to 64 years were recruited through the Surveillance, Epidemiology, and End Results registries in New Mexico (non-Hispanic white and Hispanic white), Los Angeles County (black), and Western Washington (non-Hispanic white) and followed for a median of 10.2 years. We evaluated sociodemographic factors, breast cancer- and treatment-related factors, comorbidities, body mass index (BMI), hormonal factors, and lifestyle factors in relation to self-reported lymphedema by fitting Cox proportional hazards models, estimating hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Over the follow-up period, 190 women (29%) reported lymphedema. The median time from breast cancer diagnosis to onset of lymphedema was 10.5 months (range: 0.5 to 134.9 months). Factors independently associated with lymphedema were total/modified radical mastectomy (versus partial/less than total mastectomy; HR = 1.37, 95% CI: 1.01 to 1.85), chemotherapy (versus no chemotherapy; HR = 1.48, 95% CI: 1.09 to 2.02), no lymph nodes removed (versus ≥10 lymph nodes removed; HR = 0.17, 95% CI: 0.08 to 0.33), pre-diagnostic BMI ≥30 kg/m(2) (versus BMI <25 kg/m(2); HR = 1.59, 95% CI: 1.09 to 2.31), and hypertension (versus no hypertension; HR = 1.49, 95% CI: 1.06 to 2.10). After adjusting for demographics and breast cancer- and treatment-related factors, no significant difference in lymphedema risk was observed across racial/ethnic groups. Analyses stratified by race/ethnicity showed that hypertension and chemotherapy were lymphedema risk factors only for black women. CONCLUSIONS: Breast cancer patients who have undergone extensive surgery or extensive lymph node dissection, or who have a higher BMI should be closely monitored for detection and treatment of lymphedema. Further studies are needed to understand the roles of chemotherapy and hypertension in the development of lymphedema. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-014-0414-x) contains supplementary material, which is available to authorized users

Gut Microbial Protein Expression in Response to Dietary Patterns in a Controlled Feeding Study: A Metaproteomic Approach

Although the gut microbiome has been associated with dietary patterns linked to health, microbial metabolism is not well characterized. This ancillary study was a proof of principle analysis for a novel application of metaproteomics to study microbial protein expression in a controlled dietary intervention. We measured the response of the microbiome to diet in a randomized crossover dietary intervention of a whole-grain, low glycemic load diet (WG) and a refined-grain, high glycemic load diet (RG). Total proteins in stools from 9 participants at the end of each diet period

Circulating Fatty Acids and Prostate Cancer Risk: Individual Participant Meta-Analysis of Prospective Studies

Background: Individual studies have suggested that some circulating fatty acids are associated with prostate cancer risk, but have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease. Methods: Principal investigators of prospective studies on circulating fatty acids and prostate cancer were invited to collaborate. Investigators provided individual participant data on circulating fatty acids (weight percent) and other characteristics of prostate cancer cases and controls. Prostate cancer risk by study-specific fifths of 14 fatty acids was estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided. Results: Five thousand and ninety-eight case patients and 6649 control patients from seven studies with an average follow-up of 5.1 (SD = 3.3) years were included. Stearic acid (18:0) was inversely associated with total prostate cancer (odds ratio [OR] Q5 vs Q1 = 0.88, 95% confidence interval [CI] = 0.78 to 1.00, P trend = .043). Prostate cancer risk was, respectively, 14% and 16% greater in the highest fifth of eicosapentaenoic acid (20:5n-3) (OR = 1.14, 95% CI = 1.01 to 1.29, P trend = .001) and docosapentaenoic acid (22:5n-3) (OR = 1.16, 95% CI = 1.02 to 1.33, P trend = .003), but in each case there was heterogeneity between studies (P = .022 and P < .001, respectively). There was heterogeneity in the association between docosapentaenoic acid and prostate cancer by grade of disease (P = .006); the association was statistically significant for low-grade disease but not high-grade disease. The remaining 11 fatty acids were not statistically associated with total prostate cancer risk. Conclusion: There was no strong evidence that circulating fatty acids are important predictors of prostate cancer risk. It is not clear whether the modest associations of stearic, eicosapentaenoic, and docosapentaenoic acid are causal