RESUMO
BACKGROUND: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons. RESULTS: Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5-Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk. CONCLUSION: Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer.
Assuntos
Neoplasias do Endométrio , Ácido gama-Linolênico , Humanos , Feminino , Animais , Estudos Prospectivos , Ácidos Graxos , Fatores de Risco , Dieta/efeitos adversos , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologiaRESUMO
BACKGROUND: The influence of nutrition on breast cancer prognosis is still inconclusive and therefore dietary interventions incorporating dietary biomarkers are needed to confirm compliance with dietary goals and clarify biological mechanisms. The present study assessed whether a lifestyle intervention in breast cancer survivors could affect dietary biomarkers of fruit and vegetables and fatty acids. METHODS: In this phase II single-arm trial, 37 overweight/obese early stage breast cancer patients completed a 12-week diet and exercise intervention. The intervention involved 1-h weekly diet sessions delivered by a dietician and 75-min bi-weekly physical activity sessions of moderate-to-high intensity led by trained monitors. Before and after the intervention, three 24-h dietary recalls were carried out to calculate nutrient intakes and, in addition, blood samples were taken to measure plasma carotenoids, vitamin E and retinol concentrations and erythrocyte membrane fatty acid (EFA) composition. Wilcoxon signed rank tests were used to assess changes in dietary and biomarkers measurements over the intervention period. RESULTS: After the intervention, there was a significant increase in the intake of dietary carotenoids (+15.1% compared to baseline) but not plasma carotenoids levels (+6.3%). Regarding the EFA levels, we observed a significant decrease in percentage of saturated fatty acids (-1.4%) and n-6 polyunsaturated fatty acids (-2.9%) and an increase in monounsaturated fatty acids (1.7%) and total and long-chain n-3 polyunsaturated fatty acids (by 13.1% and 13.7%, respectively). A favourable decrease in the ratio of long-chain n-6 to n-3 polyunsaturated fatty acids (-9.1%) was also observed. CONCLUSIONS: After a short-term diet and exercise intervention in overweight/obese breast cancer survivors, we observed significant changes in dietary nutrients and fatty acid biomarkers, suggesting positive dietary changes that could be relevant for breast cancer prognosis.
Assuntos
Neoplasias da Mama/sangue , Carotenoides/sangue , Dieta/métodos , Membrana Eritrocítica/metabolismo , Ácidos Graxos/análise , Estilo de Vida , Adulto , Biomarcadores/sangue , Neoplasias da Mama/complicações , Sobreviventes de Câncer/psicologia , Dieta/psicologia , Ingestão de Energia , Exercício Físico , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/terapia , Sobrepeso/sangue , Sobrepeso/complicações , Sobrepeso/terapia , Cooperação do Paciente , Resultado do Tratamento , Adulto JovemRESUMO
There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from375 incident pancreatic cancer cases and375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval] = 0.41-0.98; ptrend = 0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 = 0.60; 95%CI = 0.39-0.92; ptrend = 0.02) and docosapentaenoic acid (ORT3-T1 = 0.52; 95%CI = 0.32-0.85; ptrend = 0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 = 3.00; 95%CI = 1.13-7.99; ptrend = 0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 = 0.37; 95%CI = 0.17-0.81; ptrend = 0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 = 3.40; 95%CI = 1.39-8.34; ptrend = 0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking.
Assuntos
Ácidos Graxos/sangue , Neoplasias Pancreáticas/sangue , Fosfolipídeos/sangue , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/epidemiologia , RiscoRESUMO
Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1 = 1.26; 95% CI 1.00-1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1 = 1.29; 95% CI 1.02-1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.
Assuntos
Neoplasias da Mama/epidemiologia , Deficiência de Ácido Fólico/epidemiologia , Ácido Fólico/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Deficiência de Vitamina B 12/epidemiologia , Vitamina B 12/sangue , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Biomarcadores/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/química , Neoplasias da Mama/genética , Estudos de Casos e Controles , Dieta , Estrogênios , Europa (Continente)/epidemiologia , Feminino , Deficiência de Ácido Fólico/sangue , Seguimentos , Genes erbB-2 , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/sangue , Neoplasias Hormônio-Dependentes/epidemiologia , Polimorfismo de Nucleotídeo Único , Progesterona , Fatores de Risco , Deficiência de Vitamina B 12/sangueRESUMO
BACKGROUND: Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting. MATERIALS AND METHODS: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours. RESULTS: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor. CONCLUSION: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Dieta , Ácidos Graxos/sangue , Fosfolipídeos/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Europa (Continente) , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Fatores de RiscoRESUMO
This study aimed to examine the association between vitamin B6, folate and vitamin B12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6:n-3 ratio, trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 µmol/l of EPA (P value <0·01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2·06 µmol/l of DHA (P value <0·05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.
Assuntos
Ácidos Graxos/sangue , Ácido Fólico/sangue , Inquéritos Epidemiológicos , Vitamina B 12/sangue , Adolescente , Biomarcadores , Criança , Europa (Continente) , Ácidos Graxos/metabolismo , Feminino , Humanos , MasculinoRESUMO
The incidence of breast cancer (BC) is rising worldwide, with an increase in aggressive neoplasias in young women. Traditionally, BC in young women has been thought to be etiologically driven, primarily by genetic/hereditary factors. However, these factors explain only a small proportion of BCs, pointing to a role of the environment. Suspected factors responsible for this increase include lifestyle changes, notably alcohol consumption, diet with high intake of refined carbohydrates and saturated fat and low intake of polyunsaturated fatty acids (PUFA), fiber and vitamins (such as folate, vitamin D, and carotenoids), low physical activity, and body fatness, all of which may act from childhood and adolescent years through adulthood. Despite limited data on BC in young women, evidence points to the importance of a healthy lifestyle, including high intake of vegetables, fruits, legumes, fish, and poultry, low intake of sugar and fat, daily physical activity, low alcohol consumption, steady weight, and breastfeeding in preventing BC in young women. Preventive efforts should begin in early life to provide important benefits much later in life by shifting the long-term trajectory of risk accumulation. Data from Latin America and developing regions are still sparse. There is a need to harmonize studies in a global effort to fight the rise of BC incidence in low- and middle-income countries, where the nutritional transition is occurring rapidly. The stratification of BC by specific tumor characteristics needs to be considered since risk factors may be more particularly associated with the promotion of, or protection from, a defined type of BC.
Assuntos
Neoplasias da Mama/epidemiologia , Dieta , Estilo de Vida , Tecido Adiposo/fisiologia , Adulto , Idade de Início , Aleitamento Materno , Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Exercício Físico/fisiologia , Feminino , Saúde Global , Humanos , Fatores de RiscoRESUMO
BACKGROUND: Previous studies have relied predominantly on the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) to assess the association of adiposity with the risk of death, but few have examined whether the distribution of body fat contributes to the prediction of death. METHODS: We examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). We used a Cox regression analysis, with age as the time variable, and stratified the models according to study center and age at recruitment, with further adjustment for educational level, smoking status, alcohol consumption, physical activity, and height. RESULTS: During a mean follow-up of 9.7 years, 14,723 participants died. The lowest risks of death related to BMI were observed at a BMI of 25.3 for men and 24.3 for women. After adjustment for BMI, waist circumference and waist-to-hip ratio were strongly associated with the risk of death. Relative risks among men and women in the highest quintile of waist circumference were 2.05 (95% confidence interval [CI], 1.80 to 2.33) and 1.78 (95% CI, 1.56 to 2.04), respectively, and in the highest quintile of waist-to-hip ratio, the relative risks were 1.68 (95% CI, 1.53 to 1.84) and 1.51 (95% CI, 1.37 to 1.66), respectively. BMI remained significantly associated with the risk of death in models that included waist circumference or waist-to-hip ratio (P<0.001). CONCLUSIONS: These data suggest that both general adiposity and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-to-hip ratio in addition to BMI in assessing the risk of death.
Assuntos
Abdome/anatomia & histologia , Adiposidade , Mortalidade , Circunferência da Cintura , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Estatura , Índice de Massa Corporal , Europa (Continente)/epidemiologia , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/mortalidade , Modelos de Riscos Proporcionais , Risco , Fumar/epidemiologia , Relação Cintura-QuadrilRESUMO
BACKGROUND: Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk. METHODS: We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337,802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer. RESULTS: After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83-1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74-0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk. CONCLUSION: Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk.
Assuntos
Neoplasias Colorretais/etiologia , Anticoncepcionais Orais/efeitos adversos , Reprodução , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , RiscoRESUMO
BACKGROUND: There is increasing evidence that folate, an important component of one-carbon metabolism, modulates the epigenome. Alcohol, which can disrupt folate absorption, is also known to affect the epigenome. We investigated the association of dietary folate and alcohol intake on leukocyte DNA methylation levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Leukocyte genome-wide DNA methylation profiles on approximately 450,000 CpG sites were acquired with Illumina HumanMethylation 450K BeadChip measured among 450 women control participants of a case-control study on breast cancer nested within the EPIC cohort. After data preprocessing using surrogate variable analysis to reduce systematic variation, associations of DNA methylation with dietary folate and alcohol intake, assessed with dietary questionnaires, were investigated using CpG site-specific linear models. Specific regions of the methylome were explored using differentially methylated region (DMR) analysis and fused lasso (FL) regressions. The DMR analysis combined results from the feature-specific analysis for a specific chromosome and using distances between features as weights whereas FL regression combined two penalties to encourage sparsity of single features and the difference between two consecutive features. RESULTS: After correction for multiple testing, intake of dietary folate was not associated with methylation level at any DNA methylation site, while weak associations were observed between alcohol intake and methylation level at CpG sites cg03199996 and cg07382687, with qval = 0.029 and qval = 0.048, respectively. Interestingly, the DMR analysis revealed a total of 24 and 90 regions associated with dietary folate and alcohol, respectively. For alcohol intake, 6 of the 15 most significant DMRs were identified through FL. CONCLUSIONS: Alcohol intake was associated with methylation levels at two CpG sites. Evidence from DMR and FL analyses indicated that dietary folate and alcohol intake may be associated with genomic regions with tumor suppressor activity such as the GSDMD and HOXA5 genes. These results were in line with the hypothesis that epigenetic mechanisms play a role in the association between folate and alcohol, although further studies are warranted to clarify the importance of these mechanisms in cancer.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias da Mama/genética , Metilação de DNA , Ácido Fólico/efeitos adversos , Estudo de Associação Genômica Ampla/métodos , Leucócitos/química , Adulto , Idoso , Estudos de Casos e Controles , Ilhas de CpG , Epigênese Genética , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos Nutricionais , Estudos ProspectivosRESUMO
BACKGROUND: The relationship between erythrocyte membrane fatty acids and postmenopausal breast cancer risk was analyzed previously only by retrospective studies, which suggested a protective effect of increased saturation index (SI), i.e., the ratio of membrane stearic to oleic acid. We investigated the relationships in a prospective study of hormones, diet, and prediagnostic breast cancer (the ORDET study) conducted in northern Italy. METHODS: A total of 4052 postmenopausal women were followed for an average of 5.5 years; 71 cases of invasive breast cancer were identified. For each case subject, two matched control subjects were chosen randomly from among cohort members. The various fatty acids in erythrocyte membranes were measured as a percentage of total fatty acids. Conditional logistic regression analysis evaluated the association between membrane fatty acid composition and breast cancer risk. The SI, which is influenced by the activity of the enzyme delta 9 desaturase (Delta 9-d), was also investigated. All statistical tests were two-sided. RESULTS: Oleic (highest versus lowest tertile of percentage of total fatty acids, odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.24 to 6.28) and monounsaturated fatty acids (highest to lowest tertile, OR = 5.21; 95% CI = 1.95 to 13.91) were positively associated with breast cancer risk. The SI (highest to lowest tertile, OR = 0.29; 95% CI = 0.13 to 0.64) was inversely associated with breast cancer risk. The analysis suggested an inverse association between total polyunsaturated fatty acids and breast cancer risk, but individual polyunsaturated fatty acids behaved differently. There was no association between saturated fatty acids and breast cancer risk. CONCLUSIONS: We have found that monounsaturated fats and SI in erythrocyte membranes are predictors of postmenopausal breast cancer. Both of these variables depend on the activity of the enzyme Delta 9-d. The dietary, metabolic, and hormonal factors acting on Delta 9-d expression and activity and, therefore, on patterns of fatty acid metabolism, should be further investigated as possible determinants of breast cancer.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Membrana Eritrocítica/metabolismo , Ácidos Graxos/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Estudos de Casos e Controles , Ácidos Graxos/sangue , Ácidos Graxos Monoinsaturados/metabolismo , Ácidos Graxos Insaturados/metabolismo , Feminino , Humanos , Itália , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sistema de RegistrosRESUMO
BACKGROUND: There is limited evidence on the association between dietary folate intake and the risk of breast cancer (BC) by hormone receptor expression in the tumors. We investigated the relationship between dietary folate and BC risk using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: A total of 367993 women age 35 to 70 years were recruited in 10 European countries. During a median follow-up of 11.5 years, 11575 women with BC were identified. Dietary folate intake was estimated from country-specific dietary questionnaires. Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk. BC tumors were classified by receptor status. Subgroup analyses were performed by menopausal status and alcohol intake. Intake of other B vitamins was considered. All statistical tests were two-sided. RESULTS: A borderline inverse association was observed between dietary folate and BC risk (hazard ratio comparing top vs bottom quintile [HRQ5-Q1] = 0.92, 95% CI = 0.83 to 1.01, P trend = .037). In premenopausal women, we observed a statistically significant trend towards lower risk in estrogen receptor-negative BC (HRQ5-Q1 = 0.66, 95% CI = 0.45 to 0.96, P trend = .042) and progesterone receptor-negative BC (HRQ5-Q1 = 0.70, 95% CI = 0.51 to 0.97, P trend = .021). No associations were found in postmenopausal women. A 14% reduction in BC risk was observed when comparing the highest with the lowest dietary folate tertiles in women having a high (>12 alcoholic drinks/week) alcohol intake (HRT3-T1 = 0.86, 95% CI = 0.75 to 0.98, P interaction = .035). CONCLUSIONS: Higher dietary folate intake may be associated with a lower risk of sex hormone receptor-negative BC in premenopausal women.
Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , Ácido Fólico/administração & dosagem , Complexo Vitamínico B/administração & dosagem , Adulto , Idoso , Neoplasias da Mama/química , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Razão de Chances , Pré-Menopausa , Estudos Prospectivos , Receptores de Estrogênio/análiseRESUMO
The effects of lipid peroxidation and the antioxidant vitamin E contained in LDL isolated from control plasma (LDL--) and from plasma preincubated with 0.5 mmol/ml alpha-tocopherol (LDL+) on the proliferation of estrogen-receptor positive (ER+ : ZR-75, T-47-D, MCF-7) and negative (ER--: HBL-100, MDA-MB-231) human breast cancer cells were studied. Human skin fibroblasts served as controls. Incubation of plasma with 0.5 mmol/ml alpha-tocopherol resulted in a 3-fold increase of its content and a significant reduction in lipid hydroperoxides and conjugated dienes in LDL. Incubation of fibroblasts or ER+ tumor cells with LDL- or LDL+ had an effect on neither cell proliferation nor on the cellular levels of peroxidation products as compared to control incubations in the absence of LDL. In ER- cells, however, LDL+ stimulated the proliferation, whereas LDL- yielded a cytotoxic effect. Moreover, LDL- supplementation resulted in an increase in the content of hydroperoxides and conjugated dienes. LDL+ supplemented cells exhibited hydroperoxide levels in these tumor cells comparable to the basal levels measured in the absence of LDL. Our data suggested that peroxidation products in LDL are cytotoxic to estrogen-receptor negative breast tumor cells and vitamin E counteracts this effect.
Assuntos
Divisão Celular , Lipoproteínas LDL/farmacologia , Neoplasias da Mama/metabolismo , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular , Fibroblastos , Humanos , Peroxidação de Lipídeos/fisiologia , Peróxidos Lipídicos/metabolismo , Peróxidos Lipídicos/toxicidade , Receptores de Estrogênio/metabolismo , Células Tumorais Cultivadas , Vitamina E/farmacologiaRESUMO
Data derived from experimental studies suggest that alpha-linolenic acid may have a protective effect in breast cancer. Observations obtained from epidemiological studies have not allowed conclusions to be drawn about a potential protective effect of dietary alpha-linolenic acid on breast cancer, possibly because of methodological issues. This case-control study conducted in an homogeneous population from a central area in France was designed to explore the hypothesis that alpha-linolenic acid inhibits breast cancer, using fatty acid levels in adipose breast tissue as a biomarker of past qualitative dietary intake of fatty acids. Biopsies of adipose breast tissue at the time of diagnosis were obtained from 123 women with invasive non-metastatic breast carcinoma. 59 women with benign breast disease served as controls. Individual fatty acids were analysed by capillary gas chromatography. An unconditional logistic regression model was used to obtain odds ratio estimates whilst adjusting for age, menopausal status and body mass index (BMI). No association was found between fatty acids (saturates, monounsaturates, long-chain polyunsaturates n-6 or n-3) and the disease, except for alpha-linolenic acid which showed an inverse association with the risk of breast cancer. The relative risk of breast cancer for women in the highest quartile of adipose breast tissue alpha-linolenic acid level was 0.36 (95% confidence interval=0.12-1.02) compared with those in the lowest quartile (P trend=0.026), suggesting a protective effect of alpha-linolenic acid in the risk of breast cancer. The effects of dietary alpha-linolenic on the risk of breast cancer warrant further study.
Assuntos
Tecido Adiposo/química , Neoplasias da Mama/química , Mama/química , Ácido alfa-Linolênico/análise , Adulto , Idoso , Doenças Mamárias/metabolismo , Estudos de Casos e Controles , Cromatografia Gasosa , Dieta , Ácidos Graxos/administração & dosagem , Ácidos Graxos/análise , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Razão de Chances , RiscoRESUMO
Despite considerable methodological advances, ideal parameters relating to the in vitro assessment of lipoprotein oxidizability are lacking. In this study, some of the more common parameters of lipid peroxidation were measured in 30 plasma samples. The following parameters were determined: conjugated dienes (method 1), reaction of lipid hydroperoxides with a methylene blue derivative (method 2), oxidation of iodide to triiodide (method 3) and an iodometric assay based on the same chemistry but modified to correct for unspecific interferences (method 4). Alpha-Tocopherol in plasma was assayed by high-pressure liquid chromatography. In addition, LDL was isolated from plasma and the susceptibility of individual LDL preparations towards copper-initiated oxidation was characterized. The amount of lipid hydroperoxides found in fresh plasma samples obtained from apparently healthy humans was dependent on the method used for the assessment. Lipid hydroperoxides measured by method 2 were: 8.6 +/- 5.8 mu M, by method 3: 5.8 +/- 1.9 mu M and by method 4: 4.2 +/- 2.7 mu M. Mean values of conjugated dienes (method 1) were 84.6 +/- 20.9 mu M; The content of alpha-tocopherol in plasma was 23.6 +/- 3.9 mu M. Despite the differences in absolute values, a statistically significant correlation was found between values obtained by methods 1, 2 and 3, but not by method 4. An inverse relationship has been observed between the lipid hydroperoxide content in plasma obtained with method 4 and two parameters of LDL oxidation (diene concentration, rate of diene formation) but not with the lag time. Our data suggest that--among the photometric methods evaluated--method 4 might be the most specific for the measurement of plasma (and lipoprotein associated) lipid hydroperoxides.
Assuntos
Cobre/farmacologia , Peroxidação de Lipídeos/fisiologia , Peróxidos Lipídicos/sangue , Lipoproteínas LDL/sangue , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Lipoproteínas LDL/efeitos dos fármacos , Masculino , Oxirredução , Espectrofotometria/métodos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Vitamina E/sangueRESUMO
OBJECTIVE: We examined the reliability of the fatty acid composition of serum phospholipids in the New York University Women's Health Study, a prospective study of sex hormones, diet and breast cancer. DESIGN: Non-fasting serum samples collected at three yearly visits, in 46 healthy women, and stored at -80 degrees C for 7-12 y, were included in the study. Serum phospholipid fatty acid composition was measured by capillary gas chromatography. RESULTS: For the 20 individual fatty acids measured, the reliability coefficients were less than 0.50 for four, between 0.50 and 0.70 for nine, and greater than 0.70 for seven. Among the major fatty acids, arachidonic and alpha-linolenic acids had high reliability coefficients (0.71 and 0. 72, respectively), palmitic, oleic, linoleic, eicosapentaenoic and docosahexaenoic acids had intermediate coefficients (0.57, 0.69, 0. 62, 0.64 and 0.66, respectively), whereas stearic acid had the lowest coefficient (0.15). The reliability coefficients for total monounsaturated fats, omega-6 and omega-3 fatty acids were moderately high (0.66, 0.53 and 0.66, respectively), whereas the coefficients for total saturated fats and total polyunsaturated fats were low (0.31 and 0.43, respectively). CONCLUSIONS: These results indicate that the fatty acid composition of serum phospholipids can be a useful tool in epidemiologic studies, although for most fatty acids a single determination is associated with some error in measurement that should be taken into account at the design and analysis stages. Storage for up to 12 y at -80 degrees C preserved polyunsaturated fatty acids from oxidation very well.
Assuntos
Ácidos Graxos/sangue , Fosfolipídeos/sangue , Adulto , Idoso , Ácido Araquidônico/sangue , Cromatografia Gasosa/métodos , Registros de Dieta , Gorduras na Dieta/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Controle de Qualidade , Reprodutibilidade dos Testes , Ácido alfa-Linolênico/sangueRESUMO
We conducted a first pilot study on healthy women living in two countries with different dietary habits, Granada in the south of Spain and Malmö in the south of Sweden, in order to compare their levels of plasma phospholipid fatty acids, and to examine the relationship between the differences in food consumption. This study is part of a pilot study which is nested in the European Prospective Investigation into Cancer and Nutrition, a multi-centre prospective cohort study on diet, plasma concentrations of antioxidants and fatty acids, and markers of oxidative stress. Thirty-nine women in Granada and thirty-eight women in Malmö, aged 45-50 years (all pre-menopausal) were selected among the female participants in the cohorts from these two countries. Individual measurements of the women's habitual diet were obtained by a food frequency questionnaire. 24-hour diet recalls were used for the standardised measurement of diet at group level. Plasma phospholipid fatty acid composition was determined by capillary gas chromatography. We found a different fatty acid profile in plasma between the two populations, with higher mean levels of palmitic acid (16:0), palmitoleic acid (16:1) (n-7), oleic acid (18:1), alpha-linolenic acid (18:3) (n-3) and eicosapentaenoic acid (20:5) (n-3), and lower mean levels of stearic acid (18:0) in Malmö compared to Granada. Women in Malmö consumed more meat, alcoholic beverages and sugar, and less fish and shellfish than women in Granada. We conclude that the fatty acid composition in plasma phospholipids is different between women from the two European centres. For polyunsaturated fatty acids, differences were observed for (n-3) fatty acids. In relation to these differences, we observed that specific food intakes, particularly meat and fish, varied between the two centres.
Assuntos
Ácidos Graxos/sangue , Comportamento Alimentar , Fosfolipídeos/química , Cromatografia Gasosa , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Carne , Rememoração Mental , Pessoa de Meia-Idade , Fosfolipídeos/sangue , Projetos Piloto , Estudos Prospectivos , Alimentos Marinhos , Espanha , Inquéritos e Questionários , SuéciaRESUMO
We conducted a cross-sectional pilot study on healthy pre-menopausal women (aged 45-50 years) living in Granada, in the south of Spain (n = 39) and Malmö, in the south of Sweden (n = 38) in order to compare their plasma carotenoid levels and to investigate the relationship between the differences in food consumption. Plasma concentrations of six carotenoids were measured using high performance liquid chromatography, habitual diet (at individual level) was estimated by food frequency questionnaires and 24-hour diet recalls were used for standardised measurement of diet at group-level. We found that women in Granada consumed more fruit and vegetables than women in Malmö. Plasma concentrations of beta-cryptoxanthin, lycopene, zeaxanthin, total carotenoids and alpha-tocopherol were higher in Granada than in Malmö, although plasma concentrations of alpha-carotene and retinol were higher in Malmö. Both within and between study centres, consumption of fruit and vegetables correlated positively with plasma concentrations of different carotenoids. The study showed that differences in consumption of fruit and vegetables between the two European centres were reflected in plasma carotenoid concentrations.