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1.
J Clin Invest ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31743112

RESUMO

BACKGROUND: Ceramides are sphingolipids that play causative roles in diabetes and heart disease, with their serum levels measured clinically as biomarkers of cardiovascular disease (CVD). METHODS: We performed targeted lipidomics on serum samples of individuals with familial coronary artery disease (CAD) (n = 462) and population-based controls (n = 212) to explore the relationship between serum sphingolipids and CAD, employing unbiased machine learning to identify sphingolipid species positively associated with CAD. RESULTS: Nearly every sphingolipid measured (n = 30 of 32) was significantly elevated in subjects with CAD compared with population controls. We generated a novel Sphingolipid Inclusive CAD risk score, termed SIC, that demarcates CAD patients independently and more effectively than conventional clinical CVD biomarkers including LDL-cholesterol and serum triglycerides. This new metric comprises several minor lipids which likely serve as measures of flux through the ceramide biosynthesis pathway, rather than the abundant deleterious ceramide species that are incorporated in other ceramide-based scores. CONCLUSION: This study validates serum ceramides as candidate biomarkers of cardiovascular disease and suggests that comprehensive sphingolipid panels be considered as measures of CVD.

2.
Am J Epidemiol ; 188(6): 991-1012, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31155658

RESUMO

The Consortium of Metabolomics Studies (COMETS) was established in 2014 to facilitate large-scale collaborative research on the human metabolome and its relationship with disease etiology, diagnosis, and prognosis. COMETS comprises 47 cohorts from Asia, Europe, North America, and South America that together include more than 136,000 participants with blood metabolomics data on samples collected from 1985 to 2017. Metabolomics data were provided by 17 different platforms, with the most frequently used labs being Metabolon, Inc. (14 cohorts), the Broad Institute (15 cohorts), and Nightingale Health (11 cohorts). Participants have been followed for a median of 23 years for health outcomes including death, cancer, cardiovascular disease, diabetes, and others; many of the studies are ongoing. Available exposure-related data include common clinical measurements and behavioral factors, as well as genome-wide genotype data. Two feasibility studies were conducted to evaluate the comparability of metabolomics platforms used by COMETS cohorts. The first study showed that the overlap between any 2 different laboratories ranged from 6 to 121 metabolites at 5 leading laboratories. The second study showed that the median Spearman correlation comparing 111 overlapping metabolites captured by Metabolon and the Broad Institute was 0.79 (interquartile range, 0.56-0.89).

3.
Curr Nutr Rep ; 8(3): 202, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31197622

RESUMO

The original version of this article was revised: "The article was published with errors on text as the author's corrections were misinterpreted."

4.
Curr Nutr Rep ; 8(3): 187-201, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31129888

RESUMO

PURPOSE OF REVIEW: Metabolomics offers several opportunities for advancement in nutritional cancer epidemiology; however, numerous research gaps and challenges remain. This narrative review summarizes current research, challenges, and future directions for epidemiologic studies of nutritional metabolomics and cancer. RECENT FINDINGS: Although many studies have used metabolomics to investigate either dietary exposures or cancer, few studies have explicitly investigated diet-cancer relationships using metabolomics. Most studies have been relatively small (≤ ~ 250 cases) or have assessed a limited number of nutritional metabolites (e.g., coffee or alcohol-related metabolites). Nutritional metabolomic investigations of cancer face several challenges in study design; biospecimen selection, handling, and processing; diet and metabolite measurement; statistical analyses; and data sharing and synthesis. More metabolomics studies linking dietary exposures to cancer risk, prognosis, and survival are needed, as are biomarker validation studies, longitudinal analyses, and methodological studies. Despite the remaining challenges, metabolomics offers a promising avenue for future dietary cancer research.

5.
J Natl Cancer Inst ; 110(6): 588-597, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29325144

RESUMO

Background: Elevated body mass index (BMI) is associated with increased risk of postmenopausal breast cancer. The underlying mechanisms, however, remain elusive. Methods: In a nested case-control study of 621 postmenopausal breast cancer case participants and 621 matched control participants, we measured 617 metabolites in prediagnostic serum. We calculated partial Pearson correlations between metabolites and BMI, and then evaluated BMI-associated metabolites (Bonferroni-corrected α level for 617 statistical tests = P < 8.10 × 10-5) in relation to invasive breast cancer. Odds ratios (ORs) of breast cancer comparing the 90th vs 10th percentile (modeled on a continuous basis) were estimated using conditional logistic regression while controlling for breast cancer risk factors, including BMI. Metabolites with the lowest P values (false discovery rate < 0.2) were mutually adjusted for one another to determine those independently associated with breast cancer risk. Results: Of 67 BMI-associated metabolites, two were independently associated with invasive breast cancer risk: 16a-hydroxy-DHEA-3-sulfate (OR = 1.65, 95% confidence interval [CI] = 1.22 to 2.22) and 3-methylglutarylcarnitine (OR = 1.67, 95% CI = 1.21 to 2.30). Four metabolites were independently associated with estrogen receptor-positive (ER+) breast cancer risk: 16a-hydroxy-DHEA-3-sulfate (OR = 1.84, 95% CI = 1.27 to 2.67), 3-methylglutarylcarnitine (OR = 1.91, 95% CI = 1.23 to 2.96), allo-isoleucine (OR = 1.76, 95% CI = 1.23 to 2.51), and 2-methylbutyrylcarnitine (OR = 1.89, 95% CI = 1.22 to 2.91). In a model without metabolites, each 5 kg/m2 increase in BMI was associated with a 14% higher risk of breast cancer (OR = 1.14, 95% CI = 1.01 to 1.28), but adding 16a-hydroxy-DHEA-3-sulfate and 3-methylglutarylcarnitine weakened this association (OR = 1.06, 95% CI = 0.93 to 1.20), with the logOR attenuating by 57.6% (95% CI = 21.8% to 100.0+%). Conclusion: These four metabolites may signal metabolic pathways that contribute to breast carcinogenesis and that underlie the association of BMI with increased postmenopausal breast cancer risk. These findings warrant further replication efforts.

6.
Am J Physiol Endocrinol Metab ; 314(2): E152-E164, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28978544

RESUMO

Intramuscular triglyceride (IMTG) concentration is elevated in insulin-resistant individuals and was once thought to promote insulin resistance. However, endurance-trained athletes have equivalent concentration of IMTG compared with individuals with type 2 diabetes, and have very low risk of diabetes, termed the "athlete's paradox." We now know that IMTG synthesis is positively related to insulin sensitivity, but the exact mechanisms for this are unclear. To understand the relationship between IMTG synthesis and insulin sensitivity, we measured IMTG synthesis in obese control subjects, endurance-trained athletes, and individuals with type 2 diabetes during rest, exercise, and recovery. IMTG synthesis rates were positively related to insulin sensitivity, cytosolic accumulation of DAG, and decreased accumulation of C18:0 ceramide and glucosylceramide. Greater rates of IMTG synthesis in athletes were not explained by alterations in FFA concentration, DGAT1 mRNA expression, or protein content. IMTG synthesis during exercise in Ob and T2D indicate utilization as a fuel despite unchanged content, whereas IMTG concentration decreased during exercise in athletes. mRNA expression for genes involved in lipid desaturation and IMTG synthesis were increased after exercise and recovery. Further, in a subset of individuals, exercise decreased cytosolic and membrane di-saturated DAG content, which may help explain insulin sensitization after acute exercise. These data suggest IMTG synthesis rates may influence insulin sensitivity by altering intracellular lipid localization, and decreasing specific ceramide species that promote insulin resistance.

7.
Br J Cancer ; 118(3): 448-457, 2018 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-29235567

RESUMO

BACKGROUND: Alcohol consumption is associated with an increased risk of several cancers. Potential mechanisms include altered oestrogen metabolism. Parent oestrogens metabolise into alternate pathways of oestrogen metabolites that may have variable effects on cancer pathogenesis. We examined associations of alcohol consumption with circulating oestrogen/oestrogen metabolites in postmenopausal women in the Women's Health Initiative (WHI)-Observational Study (OS). METHODS: We conducted a cross-sectional analysis of prediagnosis ovarian/endometrial cancer case-control data within WHI-OS (N=1864). Alcohol consumption was measured by validated food frequency questionnaire. Fasting serum parent oestrogens/oestrogen metabolites were assayed using liquid chromatography tandem mass-spectrometry. Geometric mean analyte concentrations (GM, pmol l-1) were calculated by alcohol category using inverse-probability weighted linear regression, adjusting for venepuncture age/year, race, smoking, body mass index, years since menopause, oral contraceptive duration, caffeine intake, and physical activity. RESULTS: There was evidence for a positive association between alcohol consumption and oestrone, oestradiol and 2-hydroxylation oestrogen metabolite concentrations among menopausal hormone therapy (MHT) users. We observed an association between liquor consumption and parent oestrogens among non-MHT users, who consumed larger doses of liquor than MHT users. CONCLUSIONS: Among postmenopausal women, the association between alcohol intake and parent oestrogen, but not oestrogen metabolite concentrations, may be influenced by MHT and type of alcohol.

8.
Am J Clin Nutr ; 106(4): 1131-1141, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28855223

RESUMO

Background: High sodium intake is known to increase blood pressure and is difficult to measure in epidemiologic studies.Objective: We examined the effect of sodium intake on metabolites within the DASH (Dietary Approaches to Stop Hypertension Trial)-Sodium Trial to further our understanding of the biological effects of sodium intake beyond blood pressure.Design: The DASH-Sodium Trial randomly assigned individuals to either the DASH diet (low in fat and high in protein, low-fat dairy, and fruits and vegetables) or a control diet for 12 wk. Participants within each diet arm received, in random order, diets containing high (150 nmol or 3450 mg), medium (100 nmol or 2300 mg), and low (50 nmol or 1150 mg) amounts of sodium for 30 d (crossover design). Fasting blood samples were collected at the end of each sodium intervention. We measured 531 identified plasma metabolites in 73 participants at the end of their high- and low-sodium interventions and in 46 participants at the end of their high- and medium-sodium interventions (N = 119). We used linear mixed-effects regression to model the relation between each log-transformed metabolite and sodium intake. We also combined the resulting P values with Fisher's method to estimate the association between sodium intake and 38 metabolic pathways or groups.Results: Six pathways were associated with sodium intake at a Bonferroni-corrected threshold of 0.0013 (e.g., fatty acid, food component or plant, benzoate, γ-glutamyl amino acid, methionine, and tryptophan). Although 82 metabolites were associated with sodium intake at a false discovery rate ≤0.10, only 4-ethylphenylsufate, a xenobiotic related to benzoate metabolism, was significant at a Bonferroni-corrected threshold (P < 10-5). Adjustment for coinciding change in blood pressure did not substantively alter the association for the top-ranked metabolites.Conclusion: Sodium intake is associated with changes in circulating metabolites, including gut microbial, tryptophan, plant component, and γ-glutamyl amino acid-related metabolites. This trial was registered at clinicaltrials.gov as NCT00000608.


Assuntos
Dieta , Comportamento Alimentar , Hipertensão/sangue , Metaboloma/efeitos dos fármacos , Cloreto de Sódio na Dieta/farmacologia , Sódio na Dieta/farmacologia , Adolescente , Adulto , Idoso , Aminoácidos/sangue , Pressão Sanguínea , Estudos Cross-Over , Dieta com Restrição de Carboidratos , Dieta com Restrição de Gorduras , Dieta Hipossódica , Feminino , Frutas , Microbioma Gastrointestinal , Humanos , Hipertensão/dietoterapia , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Pessoa de Meia-Idade , Extratos Vegetais/sangue , Cloreto de Sódio na Dieta/administração & dosagem , Sódio na Dieta/administração & dosagem , Verduras , Adulto Jovem
9.
Am J Clin Nutr ; 106(2): 637-649, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28659298

RESUMO

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); γ-carboxyethyl hydrochroman (γ-CEHC), a vitamin E (γ-tocopherol) derivative (OR: 1.64; 95% CI: 1.18, 2.28); and 4-androsten-3ß,17ß-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 α-hydroxyisovalerate (OR: 2.23; 95% CI: 1.50, 3.32); 3 vitamin E (tocopherol) derivatives (e.g., γ-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.


Assuntos
Neoplasias da Mama/sangue , Dieta , Gorduras na Dieta/sangue , Etanol/sangue , Ácidos Graxos/sangue , Comportamento Alimentar , Tocoferóis/sangue , Idoso , Androgênios/sangue , Animais , Biomarcadores/sangue , Neoplasias da Mama/etiologia , Manteiga , Estudos de Casos e Controles , Ácidos Decanoicos/sangue , Gorduras na Dieta/efeitos adversos , Suplementos Nutricionais , Etanol/efeitos adversos , Ácidos Graxos/efeitos adversos , Feminino , Humanos , Modelos Logísticos , Metabolômica , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores Estrogênicos/metabolismo , Fatores de Risco , Tocoferóis/efeitos adversos
10.
Br J Cancer ; 116(12): 1627-1637, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-28463959

RESUMO

BACKGROUND: The relationship between diet and survival after ovarian cancer diagnosis is unclear as a result of a limited number of studies and inconsistent findings. METHODS: We examined the association between pre-diagnostic diet and overall survival in a population-based cohort (n=811) of Australian women diagnosed with invasive epithelial ovarian cancer between 2002 and 2005. Diet was measured by validated food frequency questionnaire. Deaths were ascertained up to 31 August 2014 via medical record review and Australian National Death Index linkage. We conducted Cox proportional hazards regression analysis, controlling for diagnosis age, tumour stage, grade and subtype, residual disease, smoking status, body mass index, physical activity, marital status, and energy intake. RESULTS: We observed improved survival with highest compared with lowest quartile of fibre intake (hazard ratio (HR)=0.69, 95% CI: 0.53-0.90, P-trend=0.002). There was a suggestion of better survival for women with highest compared with lowest intake category of green leafy vegetables (HR=0.79, 95% CI: 0.62-0.99), fish (HR=0.74, 95% CI: 0.57-0.95), poly- to mono-unsaturated fat ratio (HR=0.76, 95% CI: 0.59-0.98), and worse survival with higher glycaemic index (HR=1.28, 95% CI: 1.01-1.65, P-trend=0.03). CONCLUSIONS: The associations we observed between healthy components of diet pre-diagnosis and ovarian cancer survival raise the possibility that dietary choices after diagnosis may improve survival.


Assuntos
Dieta , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/mortalidade , Idoso , Austrália/epidemiologia , Estudos de Coortes , Gorduras Insaturadas na Dieta , Fibras na Dieta , Ácidos Graxos Monoinsaturados , Feminino , Índice Glicêmico , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Modelos de Riscos Proporcionais , Alimentos Marinhos , Inquéritos e Questionários , Taxa de Sobrevida , Verduras
11.
Am J Clin Nutr ; 105(2): 450-465, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28031192

RESUMO

BACKGROUND: Healthy dietary patterns that conform to national dietary guidelines are related to lower chronic disease incidence and longer life span. However, the precise mechanisms involved are unclear. Identifying biomarkers of dietary patterns may provide tools to validate diet quality measurement and determine underlying metabolic pathways influenced by diet quality. OBJECTIVE: The objective of this study was to examine the correlation of 4 diet quality indexes [the Healthy Eating Index (HEI) 2010, the Alternate Mediterranean Diet Score (aMED), the WHO Healthy Diet Indicator (HDI), and the Baltic Sea Diet (BSD)] with serum metabolites. DESIGN: We evaluated dietary patterns and metabolites in male Finnish smokers (n = 1336) from 5 nested case-control studies within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Participants completed a validated food-frequency questionnaire and provided a fasting serum sample before study randomization (1985-1988). Metabolites were measured with the use of mass spectrometry. We analyzed cross-sectional partial correlations of 1316 metabolites with 4 diet quality indexes, adjusting for age, body mass index, smoking, energy intake, education, and physical activity. We pooled estimates across studies with the use of fixed-effects meta-analysis with Bonferroni correction for multiple comparisons, and conducted metabolic pathway analyses. RESULTS: The HEI-2010, aMED, HDI, and BSD were associated with 23, 46, 23, and 33 metabolites, respectively (17, 21, 11, and 10 metabolites, respectively, were chemically identified; r-range: -0.30 to 0.20; P = 6 × 10-15 to 8 × 10-6). Food-based diet indexes (HEI-2010, aMED, and BSD) were associated with metabolites correlated with most components used to score adherence (e.g., fruit, vegetables, whole grains, fish, and unsaturated fat). HDI correlated with metabolites related to polyunsaturated fat and fiber components, but not other macro- or micronutrients (e.g., percentages of protein and cholesterol). The lysolipid and food and plant xenobiotic pathways were most strongly associated with diet quality. CONCLUSIONS: Diet quality, measured by healthy diet indexes, is associated with serum metabolites, with the specific metabolite profile of each diet index related to the diet components used to score adherence. This trial was registered at clinicaltrials.gov as NCT00342992.


Assuntos
Biomarcadores/sangue , Dieta , Metabolômica , Idoso , Animais , Estudos de Casos e Controles , Estudos Transversais , Dieta Mediterrânea , Fibras na Dieta/administração & dosagem , Grão Comestível , Ingestão de Energia , Exercício , Jejum , Ácidos Graxos Insaturados/administração & dosagem , Finlândia , Peixes , Frutas , Humanos , Micronutrientes/administração & dosagem , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Alimentos Marinhos , Inquéritos e Questionários , Verduras , alfa-Tocoferol/sangue , beta Caroteno/sangue
12.
Am J Clin Nutr ; 104(3): 776-89, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27510537

RESUMO

BACKGROUND: Diet plays an important role in chronic disease etiology, but some diet-disease associations remain inconclusive because of methodologic limitations in dietary assessment. Metabolomics is a novel method for identifying objective dietary biomarkers, although it is unclear what dietary information is captured from metabolites found in serum compared with urine. OBJECTIVE: We compared metabolite profiles of habitual diet measured from serum with those measured from urine. DESIGN: We first estimated correlations between consumption of 56 foods, beverages, and supplements assessed by a food-frequency questionnaire, with 676 serum and 848 urine metabolites identified by untargeted liquid chromatography mass spectrometry, ultra-high performance liquid chromatography tandem mass spectrometry, and gas chromatography mass spectrometry in a colon adenoma case-control study (n = 125 cases and 128 controls) while adjusting for age, sex, smoking, fasting, case-control status, body mass index, physical activity, education, and caloric intake. We controlled for multiple comparisons with the use of a false discovery rate of <0.1. Next, we created serum and urine multiple-metabolite models to predict food intake with the use of 10-fold crossvalidation least absolute shrinkage and selection operator regression for 80% of the data; predicted values were created in the remaining 20%. Finally, we compared predicted values with estimates obtained from self-reported intake for metabolites measured in serum and urine. RESULTS: We identified metabolites associated with 46 of 56 dietary items; 417 urine and 105 serum metabolites were correlated with ≥1 food, beverage, or supplement. More metabolites in urine (n = 154) than in serum (n = 39) were associated uniquely with one food. We found previously unreported metabolite associations with leafy green vegetables, sugar-sweetened beverages, citrus, added sugar, red meat, shellfish, desserts, and wine. Prediction of dietary intake from multiple-metabolite profiles was similar between biofluids. CONCLUSIONS: Candidate metabolite biomarkers of habitual diet are identifiable in both serum and urine. Urine samples offer a valid alternative or complement to serum for metabolite biomarkers of diet in large-scale clinical or epidemiologic studies.


Assuntos
Biomarcadores/urina , Comportamento Alimentar , Dieta Saudável , Modelos Biológicos , Avaliação Nutricional , Cooperação do Paciente , Adenoma/sangue , Adenoma/diagnóstico , Adenoma/metabolismo , Adenoma/urina , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Neoplasias do Colo/sangue , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/urina , Suplementos Nutricionais , Detecção Precoce de Câncer , Feminino , Hospitais Militares , Humanos , Aprendizado de Máquina , Masculino , Maryland , Metabolômica/métodos , Pessoa de Meia-Idade , Análise de Regressão , Autorrelato
14.
Nat Rev Clin Oncol ; 13(8): 504-15, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26951041

RESUMO

Despite the potentially important roles of diet and nutrition in cancer prevention, the evidence to support these roles is widely perceived by the public and health professionals as being inconsistent. In this Review, we present the issues and challenges in conducting and interpreting diet-cancer research, including those relating to the design of epidemiological studies, dietary data collection methods, and factors that affect the outcome of intervention trials. Approaches to improve effect estimates, such as the use of biomarkers to improve the accuracy of characterizing dietary exposures, are also discussed. Nutritional and dietary patterns are complex; therefore, the use of a reductionist approach to investigations, by focusing on specific nutrients, can produce misleading information. The effects of tumour heterogeneity and the failure to appreciate the nonlinear, U-shaped relationship between micronutrients and cancer in both observational studies and clinical trials are discussed. New technologies and investigational approaches are enabling the exploration of complex interactions between genetic, epigenetic, metabolic, and gut-microbial processes that will inform our knowledge of the diet-cancer relationship. Communicating the status of the evolving science in the context of the overall scientific evidence base, and evidence-based dietary recommendations for cancer prevention, should be emphasized in guidance for the public and for individual patients.


Assuntos
Dieta , Neoplasias/prevenção & controle , Estado Nutricional , Pesquisa Biomédica/tendências , Dietoterapia/tendências , Métodos Epidemiológicos , Exercício/fisiologia , Alimentos , Previsões , Dieta Saudável , Humanos
15.
J Natl Cancer Inst ; 107(12): djv275, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26424778

RESUMO

BACKGROUND: Overweight and obesity are associated with breast cancer mortality. However, the relationship between postdiagnosis weight gain and mortality is unclear. We conducted a systematic review and meta-analysis of weight gain after breast cancer diagnosis and breast cancer-specific, all-cause mortality and recurrence outcomes. METHODS: Electronic databases identified articles up through December 2014, including: PubMed (1966-present), EMBASE (1974-present), CINAHL (1982-present), and Web of Science. Language and publication status were unrestricted. Cohort studies and clinical trials measuring weight change after diagnosis and all-cause/breast cancer-specific mortality or recurrence were considered. Participants were women age 18 years or older with stage I-IIIC breast cancer. Fixed effects analysis summarized the association between weight gain (≥5.0% body weight) and all-cause mortality; all tests were two-sided. RESULTS: Twelve studies (n = 23 832) were included. Weight gain (≥5.0%) compared with maintenance (<±5.0%) was associated with increased all-cause mortality (hazard ratio [HR] = 1.12, 95% confidence interval [CI] = 1.03 to 1.22, P = .01, I(2) = 55.0%). Higher risk of mortality was apparent for weight gain ≥10.0% (HR = 1.23, 95% CI = 1.09 to 1.39, P < .001); 5% to 10.0% weight gain was not associated with all-cause mortality (P = .40). The association was not statistically significant for those with a prediagnosis body mass index (BMI) of less than 25 kg/m(2) (HR = 1.14, 95% CI = 0.99 to 1.31, P = .07) or with a BMI of 25 kg/m(2) or higher (HR = 1.00, 95% CI = 0.86 to 1.16, P = .19). Weight gain of 10.0% or more was not associated with hazard of breast cancer-specific mortality (HR = 1.17, 95% CI = 1.00 to 1.38, P = .05). CONCLUSIONS: Weight gain after diagnosis of breast cancer is associated with higher all-cause mortality rates compared with maintaining body weight. Adverse effects are greater for weight gains of 10.0% or higher.


Assuntos
Índice de Massa Corporal , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Causas de Morte , Ganho de Peso , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Obesidade/complicações , Obesidade/mortalidade , Razão de Chances , Sobrepeso/complicações , Sobrepeso/mortalidade , Prognóstico , Fatores de Risco
16.
Nutrients ; 7(7): 5156-76, 2015 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-26132992

RESUMO

Women who are obese at the time of breast cancer diagnosis have higher overall mortality than normal weight women and some evidence implicates adiponectin and leptin as contributing to prognostic disadvantage. While intentional weight loss is thought to improve prognosis, its impact on these adipokines is unclear. This study compared the pattern of change in plasma leptin and adiponectin in overweight-to-obese post-menopausal breast cancer survivors during weight loss. Given the controversies about what dietary pattern is most appropriate for breast cancer control and regulation of adipokine metabolism, the effect of a low fat versus a low carbohydrate pattern was evaluated using a non-randomized, controlled study design. Anthropometric data and fasted plasma were obtained monthly during the six-month weight loss intervention. While leptin was associated with fat mass, adiponectin was not, and the lack of correlation between leptin and adiponectin concentrations throughout weight loss implies independent mechanisms of regulation. The temporal pattern of change in leptin but not adiponectin was affected by magnitude of weight loss. Dietary pattern was without effect on either adipokine. Mechanisms not directly related to dietary pattern, weight loss, or fat mass appear to play dominant roles in the regulation of circulating levels of these adipokines.


Assuntos
Adiponectina/sangue , Neoplasias da Mama/sangue , Leptina/sangue , Sobrepeso/sangue , Perda de Peso/fisiologia , Antropometria , Biomarcadores/sangue , Índice de Massa Corporal , Neoplasias da Mama/complicações , Neoplasias da Mama/dietoterapia , Dieta com Restrição de Carboidratos , Dieta com Restrição de Gorduras , Feminino , Humanos , Pessoa de Meia-Idade , Sobrepeso/complicações , Sobrepeso/dietoterapia , Pós-Menopausa/sangue , Prognóstico , Sobreviventes , Fatores de Tempo
17.
PLoS One ; 10(5): e0127366, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26010254

RESUMO

UNLABELLED: Body weight management is not emphasized in clinical practice guidelines for breast cancer survivors, reflecting the lack of evidence that weight loss improves prognosis. Even if this situation changes, the optimal design for weight loss interventions is unclear. We conducted a 6-month non-randomized, controlled weight loss intervention in 249 post-menopausal breast cancer survivors. This paper reports effects on two secondary endpoints, change in body weight and composition. Participants were predominantly non-Hispanic whites (89%) with a mean age of 54.9 ± 9.2 years, a mean BMI of 29.0 ± 2.6 kg/m: (2) and an average of 43 ± 5% body fat. Two dietary interventions, low fat or low carbohydrate, were investigated and consisted of a 42 day cycle of menus and recipes. Weight loss counseling and anthropometric assessment were provided at monthly clinic visits. One hundred ninety-two women completed the trial (77% retention). In comparison to the nonintervention control, both intervention arms achieved significant decreases in body weight (12.5%), body fat (27.5%), waist circumference (9.5%), and hip circumference (7.8%) (all p < 0.001) with minimal effects on lean mass (1.3% decrease). Median time to 5 and 10% weight loss was 2 (95% confidence interval = 1 to 3) and 4 (95% confidence interval = 3 to 5) months, respectively, and 23% of participants experienced ≥ 15% weight loss. Loss of body weight and fat mass was rapid and substantial irrespective of dietary approach when a structured program was provided with monthly anthropometric assessment and weight loss counseling. TRIAL REGISTRATION: ClinicalTrials.gov NCT01315483.


Assuntos
Peso Corporal/fisiologia , Neoplasias da Mama/fisiopatologia , Perda de Peso/fisiologia , Tecido Adiposo/fisiologia , Composição Corporal/fisiologia , Índice de Massa Corporal , Dieta com Restrição de Gorduras/métodos , Comportamento Alimentar/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Sobreviventes , Circunferência da Cintura/fisiologia
18.
Crit Rev Eukaryot Gene Expr ; 23(2): 159-69, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23582037

RESUMO

Body weight change is defined as one or more periods of weight gain or weight loss that can vary in terms of magnitude, timeframe over which the change(s) occurs, and the number of times the pattern changes. Epidemiological and clinical data provide evidence of increased lifetime risk for breast cancer due to adult weight gain and a reduction of risk with weight loss. These findings parallel the majority of preclinical carcinogenesis experiments in which caloric intake in excess of basal metabolic requirements in rodents permits the development of cancer in proportion to the level of caloric intake. Dieting has been unsuccessful in reducing cancer risk unless a lower body weight was maintained at the end of weight change. Based on this evidence, it is recommended that consideration be given to the inclusion of the following recommendations in clinical practice guidelines for managing lifetime risk for breast cancer: (1) maintain adult body mass index in the desirable range (18.5-24.9 kg/m2) by preventing adult weight gain in both pre- and postmenopausal women, and (2) actively monitor BMI and, when BMI is above the defined ideal range, prescribe corrective lifestyle changes until body weight returns to the target range.


Assuntos
Índice de Massa Corporal , Neoplasias da Mama/etiologia , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Adulto , Animais , Restrição Calórica , Dieta , Feminino , Humanos , Estilo de Vida , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/fisiopatologia , Fatores de Risco , Ganho de Peso , Perda de Peso
19.
Breast Cancer Res ; 14(1): R1, 2012 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-22225711

RESUMO

INTRODUCTION: Healthy body weight is an important factor for prevention of breast cancer recurrence. Yet, weight loss and weight gain are not currently included in clinical-practice guidelines for posttreatment of breast cancer. The work reported addresses one of the questions that must be considered in recommending weight loss to patients: does it matter what diet plan is used, a question of particular importance because breast cancer treatment can increase risk for cardiovascular disease. METHODS: Women who completed treatment for breast cancer were enrolled in a nonrandomized, controlled study investigating effects of weight loss achieved by using two dietary patterns at the extremes of macronutrient composition, although both diet arms were equivalent in protein: high fat, low carbohydrate versus low fat, high carbohydrate. A nonintervention group served as the control arm; women were assigned to intervention arms based on dietary preferences. During the 6-month weight-loss program, which was menu and recipe defined, participants had monthly clinical visits at which anthropometric data were collected and fasting blood was obtained for safety monitoring for plasma lipid profiles and fasting glucose. Results from 142 participants are reported. RESULTS: Adverse effects on fasting blood lipids or glucose were not observed in either dietary arm. A decrease in fasting glucose was observed with progressive weight loss and was greater in participants who lost more weight, but the effect was not statistically significant, even though it was observed across both diet groups (P = 0.21). Beneficial effects of weight loss on cholesterol (4.7%; P = 0.001), triglycerides (21.8%; P = 0.01), and low-density lipoprotein (LDL) cholesterol (5.8%; P = 0.06) were observed in both groups. For cholesterol (P = 0.07) and LDL cholesterol (P = 0.13), greater reduction trends were seen on the low-fat diet pattern; whereas, for triglycerides (P = 0.01) and high-density lipoprotein (HDL) cholesterol (P = 0.08), a decrease or increase, respectively, was greater on the low-carbohydrate diet pattern. CONCLUSIONS: Because an individual's dietary preferences can affect dietary adherence and weight-loss success, the lack of evidence of a negative effect of dietary pattern on biomarkers associated with cardiovascular risk is an important consideration in the development of breast cancer practice guidelines for physicians who recommend that their patients lose weight. Whether dietary pattern affects biomarkers that predict long-term survival is a primary question in this ongoing clinical trial.


Assuntos
Glicemia , Neoplasias da Mama/prevenção & controle , Lipídeos/sangue , Recidiva Local de Neoplasia/prevenção & controle , Obesidade/dietoterapia , Sobreviventes , Índice de Massa Corporal , Dieta Redutora , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Regressão , Resultado do Tratamento , Perda de Peso
20.
BMC Cancer ; 11: 287, 2011 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-21733177

RESUMO

BACKGROUND: Weight loss in overweight or obese breast cancer patients is associated with an improved prognosis for long term survival. However, it is not clear whether the macronutrient composition of the chosen weight loss dietary plan imparts further prognostic benefit. A study protocol is presented for a dietary intervention to investigate the effects of weight loss dietary patterns that vary markedly in fat and carbohydrate contents on biomarkers of exposure to metabolic processes that may promote tumorigenesis and that are predictive of long term survival. The study will also determine how much weight must be lost for biomarkers to change in a favorable direction. METHODS/DESIGN: Approximately 370 overweight or obese postmenopausal breast cancer survivors (body mass index: 25.0 to 34.9 kg/m²) will be accrued and assigned to one of two weight loss intervention programs or a non-intervention control group. The dietary intervention is implemented in a free living population to test the two extremes of popular weight loss dietary patterns: a high carbohydrate, low fat diet versus a low carbohydrate, high fat diet. The effects of these dietary patterns on biomarkers for glucose homeostasis, chronic inflammation, cellular oxidation, and steroid sex hormone metabolism will be measured. Participants will attend 3 screening and dietary education visits, and 7 monthly one-on-one dietary counseling and clinical data measurement visits in addition to 5 group visits in the intervention arms. Participants in the control arm will attend two clinical data measurement visits at baseline and 6 months. The primary outcome is high sensitivity C-reactive protein. Secondary outcomes include interleukin-6, tumor necrosis factor-α, insulin-like growth factor-1 (IGF), IGF binding protein-3, 8-isoprostane-F2-alpha, estrone, estradiol, progesterone, sex hormone binding globulin, adiponectin, and leptin. DISCUSSION: While clinical data indicate that excess weight for height is associated with poor prognosis for long term survival, little attention is paid to weight control in the clinical management of breast cancer. This study will provide information that can be used to answer important patient questions about the effects of dietary pattern and magnitude of weight loss on long term survival following breast cancer treatment. CLINICAL TRIAL REGISTRATION: CA125243.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/dietoterapia , Dieta Redutora , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Sobreviventes , Adiponectina/sangue , Tecido Adiposo/metabolismo , Algoritmos , Análise de Variância , Neoplasias da Mama/metabolismo , Proteína C-Reativa/metabolismo , Estrogênios/sangue , Feminino , Glucose/metabolismo , Homeostase/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Leptina/sangue , Pessoa de Meia-Idade , Obesidade/sangue , Avaliação de Resultados (Cuidados de Saúde)/métodos , Avaliação de Resultados (Cuidados de Saúde)/estatística & dados numéricos , Pós-Menopausa/sangue , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Programas de Redução de Peso/métodos , Programas de Redução de Peso/estatística & dados numéricos
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