Dietary exposure to acrylamide and breast cancer risk: results from the NutriNet-Santé cohort.

BACKGROUND: Acrylamide is classified as a probable human carcinogen by the International Agency for Research on Cancer but epidemiologic evidence on the carcinogenicity of acrylamide from dietary sources is limited. OBJECTIVES: This study aimed to investigate the associations between dietary acrylamide and breast cancer risk in the NutriNet-Santé cohort, accounting for menopausal and hormone receptor status. METHODS: This prospective cohort study included 80,597 French females (mean ± SD age at baseline: 40.8 ± 14 y) during a mean ± SD follow-up of 8.8 ± 2.3 y. Acrylamide intake was evaluated using repeated 24-h dietary records (n ± SD = 5.5 ± 3.0), linked to a comprehensive food composition database. Associations between acrylamide intake and breast cancer risk (overall, premenopausal, and postmenopausal) were assessed by Cox hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors). RESULTS: The mean ± SD dietary acrylamide intake was 30.1 ± 21.9 µg/d (main contributors: coffee, potato fries and chips, pastries, cakes, bread). During follow-up, 1016 first incident breast cancer cases were diagnosed (431 premenopausal, 585 postmenopausal). A borderline significant positive association was observed between dietary acrylamide exposure and breast cancer risk overall (HR for quartile 4 compared with 1: 1.21; 95% CI: 1.00, 1.47) and a positive association was observed with premenopausal cancer (HRQ4vs.Q1: 1.40; 95% CI: 1.04, 1.88). Restricted cubic spline analyses suggested evidence for nonlinearity of these associations, with higher HRs for intermediate (quartile 2) and high (quartile 4) exposures. Receptor-specific analyses revealed positive associations with estrogen receptor-positive breast cancer (total and premenopausal). Acrylamide intake was not associated with postmenopausal breast cancer. CONCLUSIONS: Results from this large prospective cohort study suggest a positive association between dietary acrylamide and breast cancer risk, especially in premenopausal females, and provide new insights that support continued mitigation strategies to reduce the content of acrylamide in food.This trial was registered at clinicaltrials.gov as NCT03335644.

Nutritional Factors during and after Cancer: Impacts on Survival and Quality of Life.

The French National Cancer Institute conducted a collective expertise study with researchers and clinical experts from the French Network for Nutrition And Cancer Research (NACRe Network). The objective was to update the state of knowledge on the impacts of nutritional factors on clinical endpoints during or after cancer. Data from 150 meta-analyses, pooled analyses or intervention trials and 93 cohort studies were examined; they concerned 8 nutritional factors, 6 clinical events and 20 cancer locations. This report shows that some nutritional factors have impacts on mortality and on the risks of recurrence or second primary cancer in cancer patients. Therefore, high-risk nutritional conditions can be encountered for certain cancer sites: from the diagnosis and throughout the health care pathways, weight loss (lung and esophageal cancers), malnutrition (lung, esophageal, colorectal, pancreatic, gastric and liver cancers), weight gain (colorectal, breast and kidney cancers) and alcohol consumption (upper aerodigestive cancers) should be monitored; and after cancer treatments, excess weight should be detected (colorectal, breast and kidney cancers). These situations require nutritional assessments, and even support or management by health care professionals, in the context of tertiary prevention. This report also highlights some limitations regarding the existing literature and some needs for future research.

[Impact of nutritional factors during and after cancer]. / Impact des facteurs nutritionnels pendant et après cancer.

Nutritional factors (diet, weight, alcohol, physical activity) are identified as factors having an impact on the onset of several cancer sites. Less abundant scientific data also underline their impact on the tumor progression. A review of the scientific literature was carried out by a group of experts established by the French National Cancer Institute (INCa) to better document the influence of nutritional factors during and after cancer on outcomes such as overall mortality, cancer specific mortality, recurrence, second primary cancers and quality of life. This analysis of the literature completes messages of reduction of alcohol consumption, prevention of undernutrition or excess weight and adherence to dietary recommendations, avoiding the use of dietary supplements, fasting or restrictive diets and strengthens messages promoting the practice of physical activity and the fight against sedentary lifestyle.

Diet-Related Metabolomic Signature of Long-Term Breast Cancer Risk Using Penalized Regression: An Exploratory Study in the SU.VI.MAX Cohort.

BACKGROUND: Diet has been recognized as a modifiable risk factor for breast cancer. Highlighting predictive diet-related biomarkers would be of great public health relevance to identify at-risk subjects. The aim of this exploratory study was to select diet-related metabolites discriminating women at higher risk of breast cancer using untargeted metabolomics. METHODS: Baseline plasma samples of 200 incident breast cancer cases and matched controls, from a nested case-control study within the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort, were analyzed by untargeted LC-MS. Diet-related metabolites were identified by partial correlation with dietary exposures, and best predictors of breast cancer risk were then selected by Elastic Net penalized regression. The selection stability was assessed using bootstrap resampling. RESULTS: 595 ions were selected as candidate diet-related metabolites. Fourteen of them were selected by Elastic Net regression as breast cancer risk discriminant ions. A lower level of piperine (a compound from pepper) and higher levels of acetyltributylcitrate (an alternative plasticizer to phthalates), pregnene-triol sulfate (a steroid sulfate), and 2-amino-4-cyano butanoic acid (a metabolite linked to microbiota metabolism) were observed in plasma from women who subsequently developed breast cancer. This metabolomic signature was related to several dietary exposures such as a "Western" dietary pattern and higher alcohol and coffee intakes. CONCLUSIONS: Our study suggested a diet-related plasma metabolic signature involving exogenous, steroid metabolites, and microbiota-related compounds associated with long-term breast cancer risk that should be confirmed in large-scale independent studies. IMPACT: These results could help to identify healthy women at higher risk of breast cancer and improve the understanding of nutrition and health relationship.

Saturated, mono- and polyunsaturated fatty acid intake and cancer risk: results from the French prospective cohort NutriNet-Santé.

PURPOSE: Lipid intakes such as saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids have been widely studied regarding cardiovascular health, but their relevance to cancer is unclear. Inconsistent epidemiological results may be explained by varied mechanisms involving PUFAs and redox balance, inflammatory status and cell signalling, along with interactions with other dietary components such as antioxidants, dietary fibre and more generally fruits and vegetable intakes. Therefore, this study aimed to investigate the associations between lipid intakes and cancer risk, and their potential modulation by vitamin C, vitamin E, dietary fibre and fruit and vegetable intakes. METHODS: This prospective study included 44,039 participants aged ≥ 45 years from the NutriNet-Santé cohort (2009-2017). Dietary data were collected using repeated 24 h-dietary records. Multivariable Cox models were performed to characterize associations. RESULTS: SFA intake was associated with increased overall [n = 1722 cases, HRQ5vsQ1 = 1.44 (1.10-1.87), p-trend = 0.008] and breast [n = 545 cases, HRQ5vsQ1 = 1.98 (1.24-3.17), p-trend = 0.01] cancer risks. n-6 PUFA [HRQ5vsQ1 = 0.56 (0.32-0.97), p-trend = 0.01] and MUFA (HRQ5vsQ1 = 0.41 [0.18-0.0.95), p-trend = 0.009] intakes were associated with a decreased risk of digestive cancers (n = 190 cases). Associations between n-6 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes and digestive cancer risk were modulated by dietary fibre, vitamin C and fruit and vegetable intakes. CONCLUSION: These findings suggested that SFA intake could increase overall and breast cancer risks while some unsaturated fatty acids could decrease digestive cancer risk. However, in line with mechanistic hypotheses, our results suggest that intakes of fruits and vegetables and their constituents (antioxidants, fibre) may interact with PUFAs to modulate these associations.

Fasting and weight-loss restrictive diet practices among 2,700 cancer survivors: results from the NutriNet-Santé cohort.

Nutrition is often used by cancer survivors as a lever to take charge of their own health. However, some dietary behaviors are not currently recommended for patients without medical supervision. Our study aimed at evaluating weight-loss restrictive diets and fasting practices among cancer survivors of the NutriNet-Santé cohort, as well as related socio-demographic and lifestyle factors. In October 2016, 2,741 cancer survivors had completed a specific questionnaire about their practices. Fasting and non-fasting patients (respectively dieting and non-dieting) were compared using logistic regression models. Analyses were weighted according to the age, gender, and cancer location distribution of French cancer cases. 13.8% had already practiced weight-loss restrictive diet as their diagnosis. They were more likely to be women, professionally active, overweight/obese, to use dietary supplements and to have breast cancer (all p < 0.05). 6.0% had already fasted, 3.5% as their diagnosis. They were more likely to be younger, with higher educational level, higher incomes, professionally active, to have a healthy weight, and to use dietary supplements (all p < 0.05). Fasting was associated with the opinion that such practice could improve cancer prognosis (p < 0.0001). Patients who received nutritional information from health care professionals were less likely to practice fasting or weight-loss restrictive diet (0.42[0.27-0.66], p < 0.0001 and 0.49[0.38-0.64], p < 0.0001 respectively). Our study provided original results suggesting that weight-loss restrictive diets are widely practiced by cancer survivors. Fasting was less common in our study though non negligible. Sources of nutritional information received as cancer diagnosis seemed to be a key determinant of these practices.

NMR metabolomic signatures reveal predictive plasma metabolites associated with long-term risk of developing breast cancer.

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.

Dietary iron intake and breast cancer risk: modulation by an antioxidant supplementation.

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.