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Nutritional metabolomics and breast cancer risk in a prospective study.

ABSTRACT: Background: The epidemiologic evidence for associations between dietary factors and breast cancer is weak and etiologic mechanisms are often unclear. Exploring the role of dietary biomarkers with metabolomics can potentially facilitate objective dietary characterization, mitigate errors related to self-reported diet, agnostically test metabolic pathways, and identify mechanistic mediators.Objective: The aim of this study was to evaluate associations of diet-related metabolites with the risk of breast cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.Design: We examined prediagnostic serum concentrations of diet-related metabolites in a nested case-control study in 621 postmenopausal invasive breast cancer cases and 621 matched controls in the multicenter PLCO cohort. We calculated partial Pearson correlations between 617 metabolites and 55 foods, food groups, and vitamin supplements on the basis of the 2015 Dietary Guidelines for Americans and derived from a 137-item self-administered food-frequency questionnaire. Diet-related metabolites (P-correlation < 1.47 × 10-6) were evaluated in breast cancer analyses. ORs for the 90th compared with the 10th percentile were calculated by using conditional logistic regression, with body mass index, physical inactivity, other breast cancer risk factors, and caloric intake controlled for (false discovery rate <0.2).Results: Of 113 diet-related metabolites, 3 were associated with overall breast cancer risk (621 cases): caprate (10:0), a saturated fatty acid (OR: 1.77; 95% CI = 1.28, 2.43); ?-carboxyethyl hydrochroman (?-CEHC), a vitamin E (?-tocopherol) derivative (OR: 1.64; 95% CI: 1.18, 2.28); and 4-androsten-3?,17?-diol-monosulfate (1), an androgen (OR: 1.61; 95% CI: 1.20, 2.16). Nineteen metabolites were significantly associated with estrogen receptor (ER)-positive (ER+) breast cancer (418 cases): 12 alcohol-associated metabolites, including 7 androgens and ?-hydroxyisovalerate (OR: 2.23; 95% CI: 1.50, 3.32); 3 vitamin E (tocopherol) derivatives (e.g., ?-CEHC; OR: 1.80; 95% CI: 1.20, 2.70); butter-associated caprate (10:0) (OR: 1.81; 95% CI: 1.23, 2.67); and fried food-associated 2-hydroxyoctanoate (OR: 1.46; 95% CI: 1.03, 2.07). No metabolites were significantly associated with ER-negative breast cancer (144 cases).Conclusions: Prediagnostic serum concentrations of metabolites related to alcohol, vitamin E, and animal fats were moderately strongly associated with ER+ breast cancer risk. Our findings show how nutritional metabolomics might identify diet-related exposures that modulate cancer risk. This trial was registered at clinicaltrials.gov as NCT00339495.

SUBMITTER: Playdon MC

PROVIDER: S-EPMC5525118 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Nutritional metabolomics and breast cancer risk in a prospective study.

Playdon Mary C MC Ziegler Regina G RG Sampson Joshua N JN Stolzenberg-Solomon Rachael R Thompson Henry J HJ Irwin Melinda L ML Mayne Susan T ST Hoover Robert N RN Moore Steven C SC

The American journal of clinical nutrition 20170628 2

<b>Background:</b> The epidemiologic evidence for associations between dietary factors and breast cancer is weak and etiologic mechanisms are often unclear. Exploring the role of dietary biomarkers with metabolomics can potentially facilitate objective dietary characterization, mitigate errors related to self-reported diet, agnostically test metabolic pathways, and identify mechanistic mediators.<b>Objective:</b> The aim of this study was to evaluate associations of diet-related metabolites with ...[more]

PMID: 28659298

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Project description:BackgroundHyperinsulinemia and higher insulin-like growth factors may increase breast cancer risk. We evaluated a diabetes risk reduction diet (DRRD) and breast cancer risk.ObjectivesWe prospectively evaluated the association between adherence to a DRRD and the incidence of breast cancer.MethodsWe followed 88,739 women from the Nurses' Health Study (NHS; 1980-2016) and 93,915 women from the NHSII (1991-2017). Incident breast cancer cases (n = 11,943) were confirmed with medical records, and subtypes were determined by tissue microarray data and pathology reports. Information on diet and breast cancer risk factors was repeatedly ascertained in follow-up questionnaires. A DRRD score was derived with 9 factors: lower glycemic index of diet; lower intakes of trans fat, sugar-sweetened beverages/fruit juices, and red/processed meat; higher intakes of cereal fiber, coffee, nuts, and whole fruits; and a higher ratio of polyunsaturated to saturated fat (score range: 9-45). Multivariable-adjusted hazard ratios (MVHRs) and 95% CIs were calculated with Cox proportional hazards models.ResultsBeing in the highest compared with the lowest DRRD adherence quintile was associated with a modestly lower breast cancer risk (MVHRQ5vsQ1: 0.89; 95% CI: 0.84, 0.95; P-trend = 0.0002); this was attenuated after adjusting for weight change since age 18 y (MVHRQ5vsQ1: 0.92; 95% CI: 0.87, 0.98; P-trend = 0.01). The inverse association was strongest among women with current BMI < 25 kg/m2 (MVHRQ5vsQ1: 0.89; 95% CI: 0.81, 0.98; P-trend = 0.004; P-interaction = 0.04). Among tumor molecular subtypes, the strongest inverse association was observed with basal-type tumors (MVHRQ5vsQ1: 0.67; 95% CI: 0.45, 1.01; P-trend = 0.04).ConclusionsGreater DRRD-adherence was associated with lower breast cancer risk, likely mediated by less weight gain with a DRRD; however, independently of weight change, DRRD-adherence was modestly associated with lower breast cancer risk, particularly among lean women.

Project description:BackgroundHigher circulating carotenoids are associated with lower breast cancer risk. The underlying biology remains under-explored.MethodsWe profiled 293 prediagnostic plasma metabolites in a nested case-control study (n = 887 cases) within the Nurses' Health Studies. Associations between circulating carotenoids and metabolites were identified using linear-mixed models (FDR ≤ 0.05), and we further selected metabolites most predictive of carotenoids with LASSO. Metabolic signatures for carotenoids were calculated as weighted sums of LASSO selected metabolites. We further evaluated the metabolic signatures in relation to breast cancer risk using conditional logistic-regression.ResultsWe identified 48 to 110 metabolites associated with plasma levels of α-carotene, β-carotene, β-cryptoxanthin, estimated-vitamin-A-potential, lutein/zeaxanthin, and lycopene, which included primarily positively associated metabolites implicated in immune regulation (tryptophan), redox balance (plasmalogens, glutamine), epigenetic regulations (acetylated-/methylated-metabolites), and primarily inversely associated metabolites involved in β-oxidation (carnitines; FDR ≤ 0.05). The metabolomic signatures derived for β-carotene (Q4 vs. Q1 relative risk RR = 0.74, P trend = 0.02), and estimated-vitamin-A-potential (Q4 vs. Q1 RR = 0.74, P trend = 0.02)-measured ≥10 years before diagnosis-were associated with lower breast cancer risk. Modest attenuations of RR for measured levels of β-carotene and estimated-vitamin-A-potential were seen when we adjusted for their corresponding metabolic signatures.ConclusionsMetabolites involved in immune regulation, redox balance, membrane signaling, and β-oxidation were associated with plasma carotenoids. Although some metabolites may reflect shared common food sources or compartmental colocalization with carotenoids, others may signal the underlying pathways of carotenoids-associated lowered breast cancer risk.ImpactConsumption of carotenoid-rich diet is associated with a wide-range of metabolic changes which may help to reduce breast cancer risk.

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Nutritional metabolomics and breast cancer risk in a prospective study.

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Nutritional metabolomics and breast cancer risk in a prospective study.

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