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NMR metabolomic signatures reveal predictive plasma metabolites associated with long-term risk of developing breast cancer.
Lécuyer, L, Victor Bala, A, Deschasaux, M, Bouchemal, N, Nawfal Triba, M, Vasson, MP, Rossary, A, Demidem, A, Galan, P, Hercberg, S, et al
International journal of epidemiology. 2018;(2):484-494
Abstract
BACKGROUND Combination of metabolomics and epidemiological approaches opens new perspectives for ground-breaking discoveries. The aim of the present study was to investigate for the first time whether plasma untargeted metabolomic profiles, established from a simple blood draw from healthy women, could contribute to predict the risk of developing breast cancer within the following decade and to better understand the aetiology of this complex disease. METHODS A prospective nested case-control study was set up in the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, including 206 breast cancer cases diagnosed during a 13-year follow-up and 396 matched controls. Untargeted nuclear magnetic resonance (NMR) metabolomic profiles were established from baseline plasma samples. Multivariable conditional logistic regression models were computed for each individual NMR variable and for combinations of variables derived by principal component analysis. RESULTS Several metabolomic variables from 1D NMR spectroscopy were associated with breast cancer risk. Women characterized by higher fasting plasma levels of valine, lysine, arginine, glutamine, creatine, creatinine and glucose, and lower plasma levels of lipoproteins, lipids, glycoproteins, acetone, glycerol-derived compounds and unsaturated lipids had a higher risk of developing breast cancer. P-values ranged from 0.00007 [odds ratio (OR)T3vsT1=0.37 (0.23-0.61) for glycerol-derived compounds] to 0.04 [ORT3vsT1=1.61 (1.02-2.55) for glutamine]. CONCLUSION This study highlighted associations between baseline NMR plasma metabolomic signatures and long-term breast cancer risk. These results provide interesting insights to better understand complex mechanisms involved in breast carcinogenesis and evoke plasma metabolic disorders favourable for carcinogenesis initiation. This study may contribute to develop screening strategies for the identification of at-risk women for breast cancer well before symptoms appear.
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B-Vitamin Intake from Diet and Supplements and Breast Cancer Risk in Middle-Aged Women: Results from the Prospective NutriNet-Santé Cohort.
Egnell, M, Fassier, P, Lécuyer, L, Zelek, L, Vasson, MP, Hercberg, S, Latino-Martel, P, Galan, P, Deschasaux, M, Touvier, M
Nutrients. 2017;(5)
Abstract
Experimental studies suggest a protective effect of B-vitamins on breast cancer risk, potentially modulated by alcohol intake. However, epidemiological studies are limited, especially regarding non-folate B-vitamins. Furthermore, few studies included quantitative assessment of supplemental intake. This prospective study aimed to investigate the associations between intakes of B-vitamins (dietary, supplemental, total) and breast cancer risk. 27,853 women aged ≥45 years from the NutriNet-Santé cohort (2009-2016) were included, with a median follow-up time of 4.2 years. Dietary data were collected using repeated 24 h records. A specific questionnaire assessed dietary supplement use over a 12-month period. A composition database of 8000 supplements was developed. Associations were characterized by multivariable Cox models, and 462 incident breast cancers were diagnosed. Dietary (HRQ4vs.Q1 = 0.74 (0.55, 0.99), P-trend = 0.05), supplemental (HRQ4vs.Q1 = 0.61 (0.38, 0.98), P-trend = 0.05), and total (HRQ4vs.Q1 = 0.67 (0.50, 0.91), P-trend = 0.01) pyridoxine intakes were inversely associated with breast cancer risk. Total thiamin intake was borderline inversely associated with breast cancer risk (HRper 1-unit increment = 0.78 (0.61, 1.00), P = 0.05). Statistically significant interactions between alcohol consumption and B-vitamin (thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, folate, and cobalamin) supplemental intake were observed, the latter being inversely associated with breast cancer risk in non-to-low alcohol drinkers but not in higher drinkers. This large prospective study, including quantitative assessment of supplemental intake, suggests a potential protective effect of pyridoxine and thiamin on breast cancer risk in middle-aged women.
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Dietary iron intake and breast cancer risk: modulation by an antioxidant supplementation.
Diallo, A, Deschasaux, M, Partula, V, Latino-Martel, P, Srour, B, Hercberg, S, Galan, P, Fassier, P, Guéraud, F, Pierre, FH, et al
Oncotarget. 2016;(48):79008-79016
Abstract
Experimental results suggested that iron-induced lipid peroxidation may explain the direct associations observed between red/processed meat intakes and colorectal and breast cancer risk. However, epidemiological evidence is lacking. Thus, we investigated the association between dietary iron intake and breast cancer risk, and its potential modulation by an antioxidant supplementation and lipid intake. This prospective study included 4646 women from the SU.VI.MAX trial (daily low-dose antioxidants vs. placebo). 188 incident breast cancers were diagnosed (median follow-up=12.6y). Dietary iron intake was assessed using repeated 24h dietary records. Multivariable Cox proportional hazards models were computed. Dietary iron intake was associated with an increased breast cancer risk (HRT3vs.T1=1.67 (1.02-2.71), P-trend=0.04). This association was observed in the placebo group (HRT3vs.T1=2.80 (1.42-5.54), P-trend=0.003), but not in the antioxidant-supplemented group (P-trend=0.7, P-interaction=0.1). Besides, in the placebo group, the increased breast cancer risk associated with dietary iron intake was more specifically observed in women with higher lipid intake (P-trend=0.046). These findings suggest that dietary iron intake may be associated with an increased breast cancer risk, especially in women who did not received antioxidants during the trial and who consumed more lipids. This supports the experimental results suggesting that breast cancer risk may be increased by iron-induced lipid peroxidation.
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Cholesterol and breast cancer risk: a systematic review and meta-analysis of prospective studies.
Touvier, M, Fassier, P, His, M, Norat, T, Chan, DS, Blacher, J, Hercberg, S, Galan, P, Druesne-Pecollo, N, Latino-Martel, P
The British journal of nutrition. 2015;(3):347-57
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Abstract
The objective of the present study was to conduct the first systematic review and meta-analysis of prospective studies investigating the associations between total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels and the risk of breast cancer. Relevant studies were identified in PubMed (up to January 2014). Inclusion criteria were original peer-reviewed publications with a prospective design. Random-effects models were used to estimate summary hazard ratios (HR) and 95% CI. Distinction was made between studies that did or did not exclude cancer cases diagnosed during the first years of follow-up, thereby eliminating potential preclinical bias. Overall, the summary HR for the association between TC and breast cancer risk was 0.97 (95% CI 0.94, 1.00; dose-response per 1 mmol/l increment, thirteen studies), and that between HDL-C and breast cancer risk was 0.86 (95% CI 0.69, 1.09; dose-response per 1 mmol/l increment, six studies), with high heterogeneity (I2= 67 and 47%, respectively). For studies that eliminated preclinical bias, an inverse association was observed between the risk of breast cancer and TC (dose-response HR 0.94 (95% CI 0.89, 0.99), seven studies, I2= 78%; highest v. lowest HR 0.82 (95% CI 0.66, 1.02), nine studies, I2= 81%) and HDL-C (dose-response HR 0.81 (95% CI 0.65, 1.02), five studies, I2= 30 %; highest v. lowest HR 0.82 (95% CI 0.69, 0.98), five studies, I2= 0%). There was no association observed between LDL-C and the risk of breast cancer (four studies). The present meta-analysis confirms the evidence of a modest but statistically significant inverse association between TC and more specifically HDL-C and the risk of breast cancer, supported by mechanistic plausibility from experimental studies. Further large prospective studies that adequately control for preclinical bias are needed to confirm the results on the role of cholesterol level and its fractions in the aetiology of breast cancer.
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Plasma carotenoids and retinol and overall and breast cancer risk: a nested case-control study.
Pouchieu, C, Galan, P, Ducros, V, Latino-Martel, P, Hercberg, S, Touvier, M
Nutrition and cancer. 2014;(6):980-8
Abstract
Experimental studies suggest that carotenoids and retinol may play a role in carcinogenesis, but epidemiological evidence is lacking. We investigated the prospective associations between plasma concentrations of major carotenoids and retinol, and overall and breast cancer risk. A nested case-control study included all first incident cancer cases diagnosed in the SU.VI.MAX cohort between 1994 and 2002 (n = 159 cases, 1 matched control/case). Baseline plasma concentrations of carotenoids and retinol were measured by high-performance liquid chromatography. Conditional logistic regression was used to assess odds ratios for an increase of 0.1 μmol/L [odds ratio (OR)] and 95% confidence intervals (CI). Plasma β-carotene (OR = 0.95, 95% CI = 0.90-0.99, Ptrend = 0.04) and β-cryptoxanthin concentrations (OR = 0.89, 95% CI = 0.81-0.99, Ptrend = 0.03) were inversely associated with overall cancer risk. Plasma β-cryptoxanthin concentration was inversely associated with breast cancer risk (OR = 0.83, 95% CI = 0.71-0.96, Ptrend = 0.02). The OR between plasma lycopene concentration and overall cancer risk was 1.07 (0.99-1.15), Ptrend = 0.06. This association turned significant (Ptrend = 0.01) when excluding cancer cases diagnosed during the first year of follow-up. This prospective study suggests an inverse association between plasma concentrations of β-cryptoxanthin and both overall and breast cancer risk, and an inverse association between β-carotene and overall cancer risk. The direct association between lycopene concentration and cancer risk deserves further investigation.
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Association between prediagnostic biomarkers of inflammation and endothelial function and cancer risk: a nested case-control study.
Touvier, M, Fezeu, L, Ahluwalia, N, Julia, C, Charnaux, N, Sutton, A, Méjean, C, Latino-Martel, P, Hercberg, S, Galan, P, et al
American journal of epidemiology. 2013;(1):3-13
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Abstract
Experimental and prevalent case-control studies suggest an association between biomarkers of inflammation, endothelial function, and adiposity and cancer risk, but results from prospective studies have been limited. The authors' objective was to prospectively examine the relations between these biomarkers and cancer risk. A nested case-control study was designed within the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) Study, a nationwide French cohort study, to include all first primary incident cancers diagnosed between 1994 and 2007 (n = 512). Cases were matched with randomly selected controls (n = 1,024) on sex, age (in 2-year strata), body mass index (weight (kg)/height (m)(2); <25 vs. ≥25), and SU.VI.MAX intervention group. Conditional logistic regression was used to study the associations between prediagnostic levels of high-sensitivity C-reactive protein (hs-CRP), adiponectin, leptin, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1, soluble E-selectin, and monocyte chemoattractant protein 1 and cancer risk. All statistical tests were 2-sided. Plasma sICAM-1 level was positively associated with breast cancer risk (for quartile 4 vs. quartile 1, multivariate odds ratio (OR) = 1.86, 95% confidence interval (CI): 1.06, 3.26; P(trend) = 0.048). Plasma hs-CRP level was positively associated with prostate cancer risk (for quartile 4 vs. quartile 1, multivariate OR = 3.04, 95% CI: 1.28, 7.23; P(trend) = 0.03). These results suggest that prediagnostic hs-CRP and sICAM-1 levels are associated with increased prostate and breast cancer risk, respectively.