Food Predictors of Plasma Carotenoids

Empirical prediction models that weight food frequency questionnaire (FFQ) food items by their relation to nutrient biomarker concentrations may estimate nutrient exposure better than nutrient intakes derived from food composition databases. Carotenoids may especially benefit because contributing foods vary in bioavailability and assessment validity. Our objective was to develop empirical prediction models for the major plasma carotenoids and total carotenoids and evaluate their validity compared with dietary intakes calculated from standard food composition tables. 4180 nonsmoking women in the Nurses’ Health Study (NHS) blood subcohort with previously measured plasma carotenoids were randomly divided into training (n = 2787) and testing (n = 1393) subsets. Empirical prediction models were developed in the training subset by stepwise selection from foods contributing ≥0.5% to intake of the relevant carotenoid. Spearman correlations between predicted and measured plasma concentrations were compared to Spearman correlations between dietary intake and measured plasma concentrations for each carotenoid. Three to 12 foods were selected for the α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin, lycopene, and total carotenoids prediction models. In the testing subset, Spearman correlations with measured plasma concentrations for the calculated dietary intakes and predicted plasma concentrations, respectively, were 0.31 and 0.37 for α-carotene, 0.29 and 0.31 for β-carotene, 0.36 and 0.41 for β-cryptoxanthin, 0.28 and 0.31 for lutein/zeaxanthin, 0.22 and 0.23 for lycopene, and 0.22 and 0.27 for total carotenoids. Empirical prediction models may modestly improve assessment of some carotenoids, particularly α-carotene and β-cryptoxanthin

Within-person reproducibility of urinary bisphenol A and phthalate metabolites over a 1 to 3 year period among women in the Nurses’ Health Studies: a prospective cohort study

Background: Associations of bisphenol A and phthalates with chronic disease health outcomes are increasingly being investigated in epidemiologic studies. The majority of previous studies of within-person variability in urinary bisphenol A and phthalate metabolite concentrations have focused on reproducibility over short time periods. Long-term reproducibility data are needed to assess the potential usefulness of these biomarkers for prospective studies, particularly those examining risk of diseases with long latency periods. Low within-person reproducibility may attenuate relative risk estimates and reduce statistical power to detect associations with disease. Therefore, we assessed within-person reproducibility of bisphenol A, eight phthalate metabolites, and phthalic acid in spot urine samples over 1 to 3 years among women enrolled in two large cohort studies. Methods: Women in the Nurses’ Health Study and Nurses’ Health Study II provided two spot urine samples, 1 to 3 years apart (n = 80 women for analyses of bisphenol A; n = 40 women for analyses of phthalate metabolites; n = 34 women for analyses of phthalic acid). To measure within-person reproducibility, we calculated Spearman rank correlation coefficients and intraclass correlation coefficients for creatinine-adjusted concentrations of bisphenol A, phthalate metabolites, and phthalic acid. Results: Over 1 to 3 years, within-person variability of bisphenol A was high relative to total variability (intraclass correlation coefficient = 0.14) and rankings of bisphenol A levels between time-points were weakly correlated (Spearman correlation = 0.19). Seven of the eight phthalate metabolites and phthalic acid demonstrated moderate within-person stability over time (Spearman correlation or intraclass correlation coefficient = 0.39-0.55). Restricting analyses to first-morning urine samples did not alter results. Conclusions: Single measurements of bisphenol A in spot urine samples were highly variable within women over 1 to 3 years, indicating that investigation of associations between a single urinary bisphenol A measurement and disease risk may be challenging in epidemiologic studies. The majority of urinary phthalate metabolites and phthalic acid appeared moderately reproducible within women over time, suggesting single measurements may be useful in epidemiologic studies, although observed relative risks can be substantially attenuated

Flavonoid Intake and Plasma Sex Steroid Hormones, Prolactin, and Sex Hormone-Binding Globulin in Premenopausal Women

Background: Flavonoids potentially exert anti-cancer effects, as suggested by their chemical structures and supported by animal studies. In observational studies, however, the association between flavonoids and breast cancer, and potential underlying mechanisms, remain unclear. Objective: To examine the relationship between flavonoid intake and sex hormone levels using timed blood samples in follicular and luteal phases in the Nurses’ Health Study II among premenopausal women. Methods: Plasma concentrations of estrogens, androgens, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), prolactin, and sex hormone-binding globulin (SHBG) were measured in samples collected between 1996 and 1999. Average flavonoid were calculated from semiquantitative food frequency questionnaires collected in 1995 and 1999. We used generalized linear models to calculate geometric mean hormone concentrations across categories of the intake of flavonoids and the subclasses. Results: Total flavonoid intake generally was not associated with the hormones of interest. The only significant association was with DHEAS (p-trend = 0.02), which was 11.1% (95% confidence interval (CI): −18.6%, −3.0%) lower comparing the highest vs. lowest quartile of flavonoid intake. In subclass analyses, the highest (vs. lowest) quartile of flavan-3-ol intake was associated with significantly lower DHEAS concentrations (−11.3% with 95% CI: −18.3%, −3.7%, p-trend = 0.01), and anthocyanin intake was associated with a significant inverse trend for DHEA (−18.0% with 95% CI: −27.9%, −6.7%, p-trend = 0.003). Conclusion: Flavonoid intake in this population had limited impact on most plasma sex hormones in premenopausal women. Anthocyanins and flavan-3-ols were associated with lower levels of DHEA and DHEAS

Association between Cutaneous Nevi and Breast Cancer in the Nurses' Health Study: A Prospective Cohort Study

Background: Cutaneous nevi are suggested to be hormone-related. We hypothesized that the number of cutaneous nevi might be a phenotypic marker of plasma hormone levels and predict subsequent breast cancer risk. Methods and Findings: We followed 74,523 female nurses for 24 y (1986–2010) in the Nurses' Health Study and estimate the relative risk of breast cancer according to the number of cutaneous nevi. We adjusted for the known breast cancer risk factors in the models. During follow-up, a total of 5,483 invasive breast cancer cases were diagnosed. Compared to women with no nevi, women with more cutaneous nevi had higher risks of breast cancer (multivariable-adjusted hazard ratio, 1.04, 95% confidence interval [CI], 0.98–1.10 for 1–5 nevi; 1.15, 95% CI, 1.00–1.31 for 6–14 nevi, and 1.35, 95% CI, 1.04–1.74 for 15 or more nevi; p for continuous trend = 0.003). Over 24 y of follow-up, the absolute risk of developing breast cancer increased from 8.48% for women without cutaneous nevi to 8.82% (95% CI, 8.31%–9.33%) for women with 1–5 nevi, 9.75% (95% CI, 8.48%–11.11%) for women with 6–14 nevi, and 11.4% (95% CI, 8.82%–14.76%) for women with 15 or more nevi. The number of cutaneous nevi was associated with increased risk of breast cancer only among estrogen receptor (ER)–positive tumors (multivariable-adjusted hazard ratio per five nevi, 1.09, 95% CI, 1.02–1.16 for ER+/progesterone receptor [PR]–positive tumors; 1.08, 95% CI, 0.94–1.24 for ER+/PR− tumors; and 0.99, 95% CI, 0.86–1.15 for ER−/PR− tumors). Additionally, we tested plasma hormone levels according to the number of cutaneous nevi among a subgroup of postmenopausal women without postmenopausal hormone use (n = 611). Postmenopausal women with six or more nevi had a 45.5% higher level of free estradiol and a 47.4% higher level of free testosterone compared to those with no nevi (p for trend = 0.001 for both). Among a subgroup of 362 breast cancer cases and 611 matched controls with plasma hormone measurements, the multivariable-adjusted odds ratio for every five nevi attenuated from 1.25 (95% CI, 0.89–1.74) to 1.16 (95% CI, 0.83–1.64) after adjusting for plasma hormone levels. Key limitations in this study are that cutaneous nevi were self-counted in our cohort and that the study was conducted in white individuals, and thus the findings do not necessarily apply to other populations. Conclusions: Our results suggest that the number of cutaneous nevi may reflect plasma hormone levels and predict breast cancer risk independently of previously known factors. Please see later in the article for the Editors' Summar

Dietary protein sources in early adulthood and breast cancer incidence: prospective cohort study

Objective: To investigate the association between dietary protein sources in early adulthood and risk of breast cancer. Design: Prospective cohort study. Setting: Health professionals in the United States. Participants: 88 803 premenopausal women from the Nurses’ Health Study II who completed a questionnaire on diet in 1991. Main outcome measure Incident cases of invasive breast carcinoma, identified through self report and confirmed by pathology report. Results: We documented 2830 cases of breast cancer during 20 years of follow-up. Higher intake of total red meat was associated with an increased risk of breast cancer overall (relative risk 1.22, 95% confidence interval 1.06 to 1.40; Ptrend=0.01, for highest fifth v lowest fifth of intake). However, higher intakes of poultry, fish, eggs, legumes, and nuts were not related to breast cancer overall. When the association was evaluated by menopausal status, higher intake of poultry was associated with a lower risk of breast cancer in postmenopausal women (0.73, 0.58 to 0.91; Ptrend=0.02, for highest fifth v lowest fifth of intake) but not in premenopausal women (0.93, 0.78 to 1.11; Ptrend=0.60, for highest fifth v lowest fifth of intake). In estimating the effects of exchanging different protein sources, substituting one serving/day of legumes for one serving/day of red meat was associated with a 15% lower risk of breast cancer among all women (0.85, 0.73 to 0.98) and a 19% lower risk among premenopausal women (0.81, 0.66 to 0.99). Also, substituting one serving/day of poultry for one serving/day of red meat was associated with a 17% lower risk of breast cancer overall (0.83, 0.72 to 0.96) and a 24% lower risk of postmenopausal breast cancer (0.76, 0.59 to 0.99). Furthermore, substituting one serving/day of combined legumes, nuts, poultry, and fish for one serving/day of red meat was associated with a 14% lower risk of breast cancer overall (0.86, 0.78 to 0.94) and premenopausal breast cancer (0.86, 0.76 to 0.98). Conclusion: Higher red meat intake in early adulthood may be a risk factor for breast cancer, and replacing red meat with a combination of legumes, poultry, nuts and fish may reduce the risk of breast cancer

Associations of aspirin and other anti-inflammatory medications with breast cancer risk by the status of COX-2 expression

BACKGROUND: We investigated the associations of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) with breast cancer risk by the status of COX-2 protein expression. METHODS: This study included 421 cases and 3,166 controls from a nested case-control study within the Nurses\u27 Health Study (NHS) and Nurses\u27 Health Study II (NHSII) cohorts. Information on medication use was first collected in 1980 (NHS) and 1989 (NHSII) and was updated biennially. Medication use was defined as none, past or current; average cumulative dose and frequency were calculated for all past or current users using data collected from all biannual questionnaires preceding the reference date. Immunochemistry for COX-2 expression was performed using commercial antibody (Cayman Chemical and Thermo Fisher Scientific). We used polychotomous logistic regression to quantify associations of aspirin and NSAIDs with the risk of COX2+ and COX2- breast cancer tumors, while adjusting for known breast cancer risk factors. All tests of statistical significance were two-sided. RESULTS: In multivariate analysis, we found no differences in associations of the aspirin exposures and NSAIDs with breast cancer risk by COX2 expression status. In stratified analyses by COX2 status, significant associations of these medications with breast cancer risk were observed for dosage of aspirin among current users in COX2- tumors (OR for \u3e 5 tablets per week vs. none 1.71, 95% CI 1.01-2.88, p-trend 0.04). Regular aspirin use was marginally associated with the risk of COX2- tumors (p-trend = 0.06). CONCLUSIONS: Our findings suggested no differences in associations of aspirin and other NSAIDs with COX2+ and COX2- tumors

Plasma 25-hydroxyvitamin D and risk of breast cancer in the Nurses' Health Study II

Introduction Experimental evidence indicates vitamin D may play an important role in breast cancer etiology but epidemiologic evidence to date is inconsistent. Vitamin D comes from dietary intake and sun exposure and plasma levels of 25-hydroxyvitamin D (25(OH)D) are considered the best measure of vitamin D status. Methods We conducted a prospective nested case-control study within the Nurses\u27 Health Study II (NHSII). Plasma samples collected in 1996 to 1999 were assayed for 25(OH)D in 613 cases, diagnosed after blood collection and before 1 June 2007, and in 1,218 matched controls. Multivariate relative risks (RR) and 95% confidence intervals (CI) were calculated by conditional logistic regression, adjusting for several breast cancer risk factors. Results No significant association was observed between plasma 25(OH)D levels and breast cancer risk (top vs. bottom quartile multivariate RR = 1.20, 95% CI (0.88 to 1.63), P-value, test for trend = 0.32). Results were similar when season-specific quartile cut points were used. Results did not change when restricted to women who were premenopausal at blood collection or premenopausal at diagnosis. Results were similar between estrogen receptor (ER)+/progesterone receptor (PR)+ and ER-/PR- tumors (P-value, test for heterogeneity = 0.51). The association did not vary by age at blood collection or season of blood collection, but did vary when stratified by body mass index (P-value, test for heterogeneity = 0.01). Conclusions Circulating 25(OH)D levels were not significantly associated with breast cancer risk in this predominantly premenopausal population

Biomarker Validation of Dietary Intervention in Two Multiethnic Populations

Introduction: Intervention studies have been designed to change dietary and lifestyle factors associated with chronic diseases, but self-reported behavior change may incorporate intervention-related bias. This study examines plasma nutrient concentration and correlations with self-reports in the Healthy Directions intervention study. The Healthy Directions intervention studies were designed to increase multivitamin use, fruit and vegetable consumption, and physical activity in working-class, multiethnic populations. Methods: Participants in both studies completed interviewer-administered questionnaires that collected information on sociodemographic and health behavior characteristics. Postintervention blood samples were collected from 209 participants and pooled in pairs within study and within intervention group. Results: We found significantly higher plasma concentrations of retinol (P = .01) and α-carotene (P = .03) in the intervention than in the usual care group. Self-reported multivitamin users had significantly higher concentrations of retinol (P < .001), β-carotene (P = .02), and α-tocopherol (P < .001). Those who reported four or more fruit and vegetable servings per day had higher lutein and zeaxanthin (P = .05) and β-cryptoxanthin (P = .05) concentrations than those consuming fewer. Plasma nutrient concentrations were associated with reported multivitamin use and fruit and vegetable intake, but the correlations were generally higher in the usual care group. Conclusion: We found significant postintervention differences in plasma carotenoid and tocopherol concentrations by treatment group, multivitamin use, and fruit and vegetable intake. However, because we only obtained postintervention blood samples, we were unable to assess preintervention-to-postintervention changes in plasma nutrients. Self-reported intakes were significantly correlated with plasma nutrient concentrations, but the strength of the correlations differed by group, suggesting some intervention-related bias in the questionnaire responses

Healthy Lifestyle in the Primordial Prevention of Cardiovascular Disease Among Young Women

AbstractBackgroundOverall mortality rates from coronary heart disease (CHD) in the United States have declined in recent decades, but the rate has plateaued among younger women. The potential for further reductions in mortality rates among young women through changes in lifestyle is unknown.ObjectivesThe aim of this study was to estimate the proportion of CHD cases and clinical cardiovascular disease (CVD) risk factors among young women that might be attributable to poor adherence to a healthy lifestyle.MethodsA prospective analysis was conducted among 88,940 women ages 27 to 44 years at baseline in the Nurses’ Health Study II who were followed from 1991 to 2011. Lifestyle factors were updated repeatedly by questionnaire. A healthy lifestyle was defined as not smoking, a normal body mass index, physical activity ≥ 2.5 h/week, television viewing ≤ 7 h/week, diet in the top 40% of the Alternative Healthy Eating Index–2010, and 0.1 to 14.9 g/day of alcohol. To estimate the proportion of CHD and clinical CVD risk factors (diabetes, hypertension, and hypercholesterolemia) that could be attributed to poor adherence to a healthy lifestyle, we calculated the population-attributable risk percent.ResultsDuring 20 years of follow-up, we documented 456 incident CHD cases. In multivariable-adjusted models, nonsmoking, a healthy body mass index, exercise, and a healthy diet were independently and significantly associated with lower CHD risk. Compared with women with no healthy lifestyle factors, the hazard ratio for CHD for women with 6 lifestyle factors was 0.08 (95% confidence interval: 0.03 to 0.22). Approximately 73% (95% confidence interval: 39% to 89%) of CHD cases were attributable to poor adherence to a healthy lifestyle. Similarly, 46% (95% confidence interval: 43% to 49%) of clinical CVD risk factor cases were attributable to a poor lifestyle.ConclusionsPrimordial prevention through maintenance of a healthy lifestyle among young women may substantially lower the burden of CVD