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.

Prospective association between adherence to the 2017 French dietary guidelines and risk of death, CVD and cancer in the NutriNet-Santé cohort.

Non-communicable diseases, such as cancers and CVD, represent a major public health concern, and diet is an important factor in their development. French dietary recommendations were updated in 2017, and an adherence score, the Programme National Nutrition Santé Guidelines Score (PNNS-GS2), has been developed and validated using a standardised procedure. The present study aimed to analyse the prospective association between PNNS-GS2 and the risk of death, cancer and CVD. Our sample consisted of French adults included in the prospective NutriNet-Santé cohort (n 67 748, 75 634 and 80 269 for the risk of death, cancer and CVD, respectively). PNNS-GS2 (range: -∞ to 14·25) was calculated from the 24-h dietary records of the first 2 years of monitoring. Association between PNNS-GS2 (in quintiles, Q) and the risk of death, cancer and CVD was studied using Cox models adjusted for the main confounding factors. The sample included 78 % of women, aged on average 44·4 years (sd 14·6) with on average 6·6 (sd 2·3) dietary records. Average PNNS-GS2 was 1·5 (sd 3·4) and median follow-up was 6·6 years for cancers and 6·2 years for CVD and deaths. PNNS-GS2 was significantly associated with the risk of death (hazard ratio (HR)Q5vsQ1: 0·77 (95 % CI 0·60, 1·00), 828 cases), cancer (HRQ5vsQ1 = 0·80 (95 % CI 0·69, 0·92), 2577 cases) and CVD (HRQ5vsQ1 0·64 (95 % CI 0·51, 0·81), 964 cases). More specifically, PNNS-GS2 was significantly associated with colorectal and breast cancer risks but not prostate cancer risk. Our results suggest that strong adherence to the 2017 French dietary recommendations is associated with a lower risk of death, cancer or CVD. This reinforces the validity of these new recommendations and will help to promote their dissemination.

Glycaemic index, glycaemic load and cancer risk: results from the prospective NutriNet-Santé cohort.

BACKGROUND: Evidence is accumulating that high dietary glycaemic index (GI) and glycaemic load (GL) are potential risk factors for several metabolic disorders (e.g. type-2 diabetes, cardiovascular diseases), but remains limited concerning cancer risk. Although, mechanistic data suggest that consuming high-GI foods may contribute to carcinogenesis through elevated blood glucose levels, insulin resistance or obesity-related mechanisms. Our objective was to study the associations between dietary GI/GL and cancer. METHODS: In total, 103 020 French adults (median age = 40.2 years) from the NutriNet-Santé cohort (2009-2020) with no cancer or diabetes at baseline were included (705 137 person-years, median follow-up time = 7.7 years). Repeated 24-h dietary records linked with a detailed food-composition table (>3500 food/beverage items). We computed the average dietary GI and GL at the individual level. Associations between GI, GL, contribution of low- and medium/high-GI foods to energy and carbohydrate intake and cancer risk (overall, breast, prostate and colorectal) were assessed using multivariable Cox proportional-hazard models. RESULTS: Higher dietary GL was associated with higher overall cancer risk [n = 3131 cases, hazard ratios (HRs) for sex-specific quintile 5 vs 1 = 1.25, 95% confidence interval (CI) = 1.03-1.52; Ptrend = 0.008] and specifically postmenopausal breast cancer (n = 924, HRQ5vs.Q1 = 1.64, 95% CI = 1.06-2.55; Ptrend = 0.03). A higher contribution of low-GI food/beverages to energy intake was associated with lower cancer risk whereas a higher contribution of medium/high-GI items to energy intake was positively associated with higher risk of overall, breast and postmenopausal breast cancers (Ptrend ≤ 0.02). CONCLUSIONS: These results support a possible impact of GI/GL on cancer risk. If confirmed in other populations and settings, dietary GI/GL could be considered as modifiable risk factors for primary cancer prevention. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03335644.

[During and after cancer: identification of high-risk nutritional situations]. / Pendant et après un cancer : repérer les situations nutritionnelles à risque.

"During and after cancer: identification of high-risk nutritional situations At the end of 2020, the French National Cancer Institute published a report presenting the state of knowledge on the impact of nutritional factors on clinical endpoints during or after cancer. This report is the result of a collective expertise by an expert group from the French Network for Nutrition And Cancer Research (NACRe Network, www.inrae.fr/nacre). This report shows that some nutritional factors have an impact on the mortality, and the risk of recurrence or second primary cancer in cancer patients. Therefore, high-risk nutritional situations can be encountered for certain cancer sites: from the diagnosis and throughout the healthcare circuit, weight loss (for lung and esophageal cancers), malnutrition (for lung, esophageal, colorectal, pancreatic, gastric and liver cancers), weight gain (for colorectal, breast and kidney cancers), or 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, or even support or management by healthcare professionals, in the context of tertiary prevention."

Pendant et après un cancer : repérer les situations nutritionnelles à risque Fin 2020, l'Institut national du cancer a publié un rapport présentant l'état actuel des connaissances sur l'impact des facteurs nutritionnels sur des événements cliniques pendant et après un cancer. Ce rapport est issu d'une d'expertise collective ayant fait appel à des experts du Réseau national alimentation cancer recherche (Réseau NACRe, www.inrae.fr/nacre). Le rapport montre que certains facteurs nutritionnels ont un impact sur la mortalité, le risque de récidive et de second cancer primitif chez les patients atteints de cancer. Ainsi, des situations nutritionnelles à risque pourraient être rencontrées pour certaines localisations du cancer  : dès le diagnostic et tout au long du parcours de soins, il convient d'être vigilant face à une éventuelle perte de poids (cancers du poumon et de l'oesophage), la dénutrition (cancers du poumon, de l'oesophage, du côlon et du rectum, du pancréas, de l'estomac et du foie), une prise de poids (cancers colorectal, du sein et du rein) ou la consommation d'alcool (cancers des voies aérodigestives supérieures)   ; et, après les traitements, à un excès de poids (cancers colorectal, du sein et du rein). Ces situations nécessitent des évaluations nutritionnelles, voire un accompagnement ou une prise en charge par des professionnels de santé, dans le cadre de la prévention tertiaire.

[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.

NMR metabolomic profiles associated with long-term risk of prostate cancer.

INTRODUCTION: Prostate cancer is a multifactorial disease whose aetiology is still not fully understood. Metabolomics, by measuring several hundred metabolites simultaneously, could enhance knowledge on the metabolic changes involved and the potential impact of external factors. OBJECTIVES: The aim of the present study was to investigate whether pre-diagnostic plasma metabolomic profiles were associated with the risk of developing a prostate cancer within the following decade. METHODS: A prospective nested case-control study was set up among the 5141 men participant of the SU.VI.MAX cohort, including 171 prostate cancer cases, diagnosed between 1994 and 2007, and 171 matched controls. Nuclear magnetic resonance (NMR) metabolomic profiles were established from baseline plasma samples using NOESY1D and CPMG sequences. Multivariable conditional logistic regression models were computed for each individual NMR signal and for metabolomic patterns derived using principal component analysis. RESULTS: Men with higher fasting plasma levels of valine (odds ratio (OR) = 1.37 [1.07-1.76], p = .01), glutamine (OR = 1.30 [1.00-1.70], p = .047), creatine (OR = 1.37 [1.04-1.80], p = .02), albumin lysyl (OR = 1.48 [1.12-1.95], p = .006 and OR = 1.51 [1.13-2.02], p = .005), tyrosine (OR = 1.40 [1.06-1.85], p = .02), phenylalanine (OR = 1.39 [1.08-1.79], p = .01), histidine (OR = 1.46 [1.12-1.88], p = .004), 3-methylhistidine (OR = 1.37 [1.05-1.80], p = .02) and lower plasma level of urea (OR = .70 [.54-.92], p = .009) had a higher risk of developing a prostate cancer during the 13 years of follow-up. CONCLUSIONS: This exploratory study highlighted associations between baseline plasma metabolomic profiles and long-term risk of developing prostate cancer. If replicated in independent cohort studies, such signatures may improve the identification of men at risk for prostate cancer well before diagnosis and the understanding of this disease.

Prospective association between dietary pesticide exposure profiles and postmenopausal breast-cancer risk in the NutriNet-Santé cohort.

BACKGROUND: Some pesticides, used in large quantities in current agricultural practices all over Europe, are suspected of adverse effects on human reproductive health (breast and prostate cancers), through mechanisms of endocrine disruption and possible carcinogenic properties, as observed in agricultural settings. However, evidence on dietary pesticide exposure and breast cancer (BC) is lacking for the general population. We aimed to assess the associations between dietary exposure to pesticides and BC risk among postmenopausal women of the NutriNet-Santé cohort. METHODS: In 2014, participants completed a self-administered semi-quantitative food-frequency questionnaire distinguishing conventional and organic foods. Exposures to 25 active substances used in EU plant-protection products were estimated using a pesticide-residue database accounting for farming practices, from Chemisches und Veterinäruntersuchungsamt Stuttgart, Germany. Non-negative matrix factorization (NMF), adapted for data with excess zeros, was used to establish exposure profiles. The four extracted NMF components' quintiles were introduced into Cox models estimating hazard ratio (HR) and 95% confidence interval (95% CI), adjusted for known confounding factors. RESULTS: A total of 13 149 postmenopausal women were included in the analysis (169 BC cases, median follow-up = 4.83 years). Negative associations between Component 3, reflecting low exposure to synthetic pesticides, and postmenopausal BC risk were found [HRQ5 = 0.57; 95% CI (0.34; 0.93), p-trend = 0.006]. Positive association between Component 1 score (highly correlated to chlorpyrifos, imazalil, malathion, thiabendazole) and postmenopausal BC risk was found specifically among overweight and obese women [HRQ5 = 4.13; 95% CI (1.50; 11.44), p-trend = 0.006]. No associations were detected for the other components. CONCLUSION: These associations suggest a potential role of dietary pesticide exposure on BC risk. Further research is needed to investigate the mechanisms and confirm these results in other populations.

Diet and physical activity during the coronavirus disease 2019 (COVID-19) lockdown (March-May 2020): results from the French NutriNet-Santé cohort study.

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19) has been spreading steadily, resulting in overwhelmed health-care systems and numerous deaths worldwide. To counter these outcomes, many countries, including France, put in place strict lockdown measures, requiring the temporary closure of all but essential places and causing an unprecedented disruption of daily life. OBJECTIVES: Our objective was to explore potential changes in dietary intake, physical activity, body weight, and food supply during the COVID-19 lockdown and how these differed according to individual characteristics. METHODS: The analyses included 37,252 adults from the French web-based NutriNet-Santé cohort who completed lockdown-specific questionnaires in April-May 2020. Nutrition-related changes and their sociodemographic, lifestyle, and health-status correlates were investigated using multivariable logistic regression models. Clusters of participants were defined using an ascending hierarchical classification of change profiles derived from multiple correspondence analyses. RESULTS: During the lockdown, trends of unfavorable changes were observed: decreased physical activity (reported by 53% of the participants), increased sedentary time (reported by 63%), increased snacking, decreased consumption of fresh food (especially fruit and fish), and increased consumption of sweets, cookies, and cakes. Yet, the opposite trends were also observed: increased home cooking (reported by 40%) and increased physical activity (reported by 19%). Additionally, 35% of the participants gained weight (mean weight gain in these individuals, 1.8 kg ± SD 1.3 kg) and 23% lost weight (2 kg ± SD 1.4 kg weight loss). All of these trends displayed associations with various individual characteristics. CONCLUSIONS: These results suggest that nutrition-related changes occurred during the lockdown in both unfavorable and favorable directions. The observed unfavorable changes should be considered in the event of a future lockdown, and should also be monitored to prevent an increase in the nutrition-related burden of disease, should these diet/physical activity changes be maintained in the long run. Understanding the favorable changes may help extend them on a broader scale. This trial was registered at clinicaltrials.gov as NCT03335644.

Modelling the number of avoidable new cancer cases in France attributable to alcohol consumption by following official recommendations: a simulation study.

AIMS: To predict the effects of perfect adherence to the French alcohol consumption guidelines, a maximum of 10 standard alcoholic drinks per week with no more than two standard alcoholic drinks per day, during a 36-year period (2014-50). DESIGN: This simulation study is an adaption of the Sheffield Alcohol Policy Model. The dose-response relationship between alcohol consumption and alcohol-attributable cancer risks was defined by cancer site-specific risk functions, each modelled as a continuous risk. These estimates were used to compute the potential impact fraction (PIF) associated with alcohol consumption by cancer site. SETTING: The French general adult population during a 36-year period (2014-50). PARTICIPANTS: For the baseline scenario, the current distribution of consumption levels, the counterfactual scenario and perfect adherence to the French alcohol consumption guidelines, we generated for each gender and age group 1000 randomly distributed alcohol consumption values from calibrated group-specific gamma distribution. MEASUREMENTS: The predicted number of new cancer cases among men and women in France between 2015 and 2050 that could have been prevented by following the French government's alcohol consumption guidelines. FINDINGS: The simulation predicted that perfect adherence to the French government's alcohol consumption guidelines would prevent, on average, an estimated 15 952 cancer cases per year after the PIF reached its full effect, which would have represented 4.5% of new cancer cases in 2015. The number of averted cancer cases over the study period were highest for oral cavity, oropharynx and hypopharynx cancer (respectively, 118 462, 95% CI = 113 803-123 022 and 11 167, 95% CI = 10 149-12 229] for men and women; liver and intrahepatic bile ducts cancer (123 447, 95% CI = 112 581-133 404 and 2825, 95% CI = 2208,4095); colorectal cancer (89 859, 95% CI = 84 651-95 355 and 12 847, 95% CI = 11 545-14 245); and female breast cancer (61 649, 95% CI = 56 330-67 452). CONCLUSION: This simulation study of the French general population predicted that perfect adherence to the French government's alcohol consumption guidelines (no more than 10 standard alcoholic drinks per week and two per day) would prevent almost 16 000 cancer cases per year.

Anxiety is a potential effect modifier of the association between red and processed meat consumption and cancer risk: findings from the NutriNet-Santé cohort.

PURPOSE: Red and processed meats are recognized by the International Agency for Research on Cancer as probably carcinogenic and carcinogenic to humans, respectively. Heme iron has been proposed as a central factor responsible for this effect. Furthermore, anxiety affects the intestinal barrier function by increasing intestinal permeability. The objective of this work was to assess how anxiety modifies the association between red and processed meat consumption and cancer risk in the NutriNet-Santé prospective cohort (2009-2019). METHODS: Using multi-adjusted Cox models in a sample of 101,269 subjects, we studied the associations between the consumption of red and processed meat, the amount of heme iron coming from these meats and overall, colorectal, prostate, and breast cancer risks, overall and separately among participants with and without anxiety. RESULTS: An increase in red and processed meat consumption was associated with an increased risk of developing colorectal cancer in the total population (HR for an increase of 50 g/day = 1.18 (1.01-1.37), p = 0.03). After stratification on anxiety, the HR 50 g/day was 1.42 (1.03-1.94, p = 0.03) in anxious participants and 1.12 (0.94-1.33, p = 0.20) in other participants. Similar trends were observed for overall cancer risk. Analyses conducted with heme iron also provided similar results. CONCLUSIONS: Our results strengthen the existing body of evidence supporting that red and processed meat consumption and heme iron intake are associated with an increased risk of overall and more specifically colorectal cancer, and suggest that anxiety modifies these associations, with an increased risk in anxious participants.

Association between nutritional profiles of foods underlying Nutri-Score front-of-pack labels and mortality: EPIC cohort study in 10 European countries.

OBJECTIVE: To determine if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality. DESIGN: Population based cohort study. SETTING: European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from 23 centres in 10 European countries. PARTICIPANTS: 521 324 adults; at recruitment, country specific and validated dietary questionnaires were used to assess their usual dietary intakes. A FSAm-NPS score was calculated for each food item per 100 g content of energy, sugars, saturated fatty acids, sodium, fibre, and protein, and of fruit, vegetables, legumes, and nuts. The FSAm-NPS dietary index was calculated for each participant as an energy weighted mean of the FSAm-NPS score of all foods consumed. The higher the score the lower the overall nutritional quality of the diet. MAIN OUTCOME MEASURE: Associations between the FSAm-NPS dietary index score and mortality, assessed using multivariable adjusted Cox proportional hazards regression models. RESULTS: After exclusions, 501 594 adults (median follow-up 17.2 years, 8 162 730 person years) were included in the analyses. Those with a higher FSAm-NPS dietary index score (highest versus lowest fifth) showed an increased risk of all cause mortality (n=53 112 events from non-external causes; hazard ratio 1.07, 95% confidence interval 1.03 to 1.10, P<0.001 for trend) and mortality from cancer (1.08, 1.03 to 1.13, P<0.001 for trend) and diseases of the circulatory (1.04, 0.98 to 1.11, P=0.06 for trend), respiratory (1.39, 1.22 to 1.59, P<0.001), and digestive (1.22, 1.02 to 1.45, P=0.03 for trend) systems. The age standardised absolute rates for all cause mortality per 10 000 persons over 10 years were 760 (men=1237; women=563) for those in the highest fifth of the FSAm-NPS dietary index score and 661 (men=1008; women=518) for those in the lowest fifth. CONCLUSIONS: In this large multinational European cohort, consuming foods with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher mortality for all causes and for cancer and diseases of the circulatory, respiratory, and digestive systems, supporting the relevance of FSAm-NPS to characterise healthier food choices in the context of public health policies (eg, the Nutri-Score) for European populations. This is important considering ongoing discussions about the potential implementation of a unique nutrition labelling system at the European Union level.

Total and added sugar intakes, sugar types, and cancer risk: results from the prospective NutriNet-Santé cohort.

BACKGROUND: Excessive sugar intake is now recognized as a key risk factor for obesity, type 2 diabetes, and cardiovascular diseases. In contrast, evidence on the sugar-cancer link is less consistent. Experimental data suggest that sugars could play a role in cancer etiology through obesity but also through inflammatory and oxidative mechanisms and insulin resistance, even in the absence of weight gain. OBJECTIVE: The objective was to study the associations between total and added sugar intake and cancer risk (overall, breast, and prostate), taking into account sugar types and sources. METHODS: In total, 101,279 participants aged >18 y (median age, 40.8 y) from the French NutriNet-Santé prospective cohort study (2009-2019) were included (median follow-up time, 5.9 y). Sugar intake was assessed using repeated and validated 24-h dietary records, designed to register participants' usual consumption for >3500 food and beverage items. Associations between sugar intake and cancer risk were assessed by Cox proportional hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors). RESULTS: Total sugar intake was associated with higher overall cancer risk (n = 2503 cases; HR for quartile 4 compared with quartile 1: 1.17; 95% CI: 1.00, 1.37; Ptrend = 0.02). Breast cancer risks were increased (n = 783 cases; HRQ4vs.Q1 = 1.51; 95% CI: 1.14, 2.00; Ptrend = 0.0007). Results remained significant when weight gain during follow-up was adjusted for. In addition, significant associations with cancer risk were also observed for added sugars, free sugars, sucrose, sugars from milk-based desserts, dairy products, and sugary drinks (Ptrend ≤ 0.01). CONCLUSIONS: These results suggest that sugars may represent a modifiable risk factor for cancer prevention (breast in particular), contributing to the current debate on the implementation of sugar taxation, marketing regulation, and other sugar-related policies. This trial was registered at clinicaltrials.gov as NCT03335644.

Associations between consumption of dietary fibers and the risk of cardiovascular diseases, cancers, type 2 diabetes, and mortality in the prospective NutriNet-Santé cohort.

BACKGROUND: Mounting evidence, yet with varying levels of proof, suggests that dietary fibers (DFs) may exert a protective role against various chronic diseases, but this might depend on the DF type and source. OBJECTIVES: Our objectives were to assess the associations between the intake of DFs of different types [total (TDF), soluble (SF), insoluble (IF)] and from different sources (fruits, vegetables, whole grains, legumes, potatoes and tubers) and the risk of cardiovascular diseases (CVDs), cancer, type 2 diabetes (T2D), and mortality in the large-scale NutriNet-Santé prospective cohort (2009-2019). METHODS: Overall, 107,377 participants were included. Usual DF intake was estimated from validated repeated 24-h dietary records over the first 2 y following inclusion in the cohort. Associations between sex-specific quintiles of DF intake and the risk of chronic diseases and mortality were assessed using multiadjusted Cox proportional hazards models. RESULTS: T2D risk was inversely associated with TDFs [HR for quintile 5 compared with quintile 1: 0.59 (95% CI: 0.42, 0.82), P-trend <0.001], SFs [HR: 0.77 (0.56, 1.08); P-trend = 0.02], and IFs [HR: 0.69 (0.50, 0.96); P-trend = 0.004]. SFs were associated with a decreased risk of CVD [HR: 0.80 (0.66, 0.98); P-trend = 0.01] and colorectal cancer [HR: 0.41 (0.21, 0.79); P-trend = 0.01]. IFs were inversely associated with mortality from cancer or CVDs [HR: 0.65 (0.45, 0.94); P-trend = 0.02]. TDF intake was associated with a decreased risk of breast cancer [HR:: 0.79 (0.54, 1.13); P-trend = 0.04]. DF intake from fruit was associated with the risk of several chronic diseases. CONCLUSIONS: Our results suggest that DF intake, especially SFs and DFs from fruits, was inversely associated with the risk of several chronic diseases and with mortality. Further studies are needed, involving different types and sources of fiber. Meanwhile, more emphasis should be put on DFs in public health nutrition policies, as DF intake remains below the recommended levels in many countries. This trial was registered at clinicaltrials.gov as NCT03335644.

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.

Diet, Physical Activity, Obesity, and Breastfeeding: How French People Perceive Factors Associated with Cancer Risk.

The French Cancer Barometer, a population-based-survey, is carried out every five years and is, to date, one of the few national studies conducted to investigate individual perception linked to cancer risk factors. The aims of the present study were to describe the perceptions of the French population in 2015 and to assess their evolution over a 5-year period (2010-2015). The French Cancer Barometer surveyed a randomly selected sample of participants aged 15-75 years (n = 3345 in 2010) and 15-85 years (n = 3764 in 2015), representative of the French population. Questions were on perception of diet, physical activity, obesity, and breastfeeding as cancer risk factors. In 2015, nutritional/activity factors were perceived as having an important role in cancer development for the majority of those surveyed (diet (90.8%), obesity (76%), and physical activity (70%)) with the exception being breastfeeding (34%). However, there was a moderate perception of the risks of red meat (43%) and salt or salty food (55%) consumption. Perceptions of nutritional risk factors were mostly associated with age and education level. Interestingly, there was a greater perception of nutritional risk factors in 2015 compared to 2010, and the participants' opinions were also stronger. Efforts should be made on individuals with lower educational level and to promote the beneficial effects of breastfeeding. However, to impact food behavior, measures are needed at the environmental level and not only at the individual one.

Sugary drink consumption and risk of cancer: results from NutriNet-Santé prospective cohort.

OBJECTIVE: To assess the associations between the consumption of sugary drinks (such as sugar sweetened beverages and 100% fruit juices), artificially sweetened beverages, and the risk of cancer. DESIGN: Population based prospective cohort study. SETTING AND PARTICIPANTS: Overall, 101 257 participants aged 18 and over (mean age 42.2, SD 14.4; median follow-up time 5.1 years) from the French NutriNet-Santé cohort (2009-2017) were included. Consumptions of sugary drinks and artificially sweetened beverages were assessed by using repeated 24 hour dietary records, which were designed to register participants' usual consumption for 3300 different food and beverage items. MAIN OUTCOME MEASURES: Prospective associations between beverage consumption and the risk of overall, breast, prostate, and colorectal cancer were assessed by multi-adjusted Fine and Gray hazard models, accounting for competing risks. Subdistribution hazard ratios were computed. RESULTS: The consumption of sugary drinks was significantly associated with the risk of overall cancer (n=2193 cases, subdistribution hazard ratio for a 100mL/d increase 1.18, 95% confidence interval 1.10 to 1.27, P<0.0001) and breast cancer (693, 1.22, 1.07 to 1.39, P=0.004). The consumption of artificially sweetened beverages was not associated with the risk of cancer. In specific subanalyses, the consumption of 100% fruit juice was significantly associated with the risk of overall cancer (2193, 1.12, 1.03 to 1.23, P=0.007). CONCLUSIONS: In this large prospective study, the consumption of sugary drinks was positively associated with the risk of overall cancer and breast cancer. 100% fruit juices were also positively associated with the risk of overall cancer. These results need replication in other large scale prospective studies. They suggest that sugary drinks, which are widely consumed in Western countries, might represent a modifiable risk factor for cancer prevention. STUDY REGISTRATION: ClinicalTrials.gov NCT03335644.

Plasma Metabolomic Signatures Associated with Long-term Breast Cancer Risk in the SU.VI.MAX Prospective Cohort.

BACKGROUND: Breast cancer is a major cause of death in occidental women. The role of metabolism in breast cancer etiology remains unclear. Metabolomics may help to elucidate novel biological pathways and identify new biomarkers to predict breast cancer long before symptoms appear. The aim of this study was to investigate whether untargeted metabolomic signatures from blood draws of healthy women could contribute to better understand and predict the long-term risk of developing breast cancer. METHODS: A nested case-control study was conducted within the SU.VI.MAX prospective cohort (13 years of follow-up) to analyze baseline plasma samples of 211 incident breast cancer cases and 211 matched controls by LC/MS. Multivariable conditional logistic regression models were computed. RESULTS: A total of 3,565 ions were detected and 1,221 were retained for statistical analysis. A total of 73 ions were associated with breast cancer risk (P < 0.01; FDR ≤ 0.2). Notably, we observed that a lower plasma level of O-succinyl-homoserine (OR = 0.70, 95%CI = [0.55-0.89]) and higher plasma levels of valine/norvaline [1.45 (1.15-1.83)], glutamine/isoglutamine [1.33 (1.07-1.66)], 5-aminovaleric acid [1.46 (1.14-1.87)], phenylalanine [1.43 (1.14-1.78)], tryptophan [1.40 (1.10-1.79)], γ-glutamyl-threonine [1.39 (1.09-1.77)], ATBC [1.41 (1.10-1.79)], and pregnene-triol sulfate [1.38 (1.08-1.77)] were associated with an increased risk of developing breast cancer during follow-up.Conclusion: Several prediagnostic plasmatic metabolites were associated with long-term breast cancer risk and suggested a role of microbiota metabolism and environmental exposure. IMPACT: After confirmation in other independent cohort studies, these results could help to identify healthy women at higher risk of developing breast cancer in the subsequent decade and to propose a better understanding of the complex mechanisms involved in its etiology.

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.

Association of Frequency of Organic Food Consumption With Cancer Risk: Findings From the NutriNet-Santé Prospective Cohort Study.

Importance: Although organic foods are less likely to contain pesticide residues than conventional foods, few studies have examined the association of organic food consumption with cancer risk. Objective: To prospectively investigate the association between organic food consumption and the risk of cancer in a large cohort of French adults. Design, Setting, and Participants: In this population-based prospective cohort study among French adult volunteers, data were included from participants with available information on organic food consumption frequency and dietary intake. For 16 products, participants reported their consumption frequency of labeled organic foods (never, occasionally, or most of the time). An organic food score was then computed (range, 0-32 points). The follow-up dates were May 10, 2009, to November 30, 2016. Main Outcomes and Measures: This study estimated the risk of cancer in association with the organic food score (modeled as quartiles) using Cox proportional hazards regression models adjusted for potential cancer risk factors. Results: Among 68 946 participants (78.0% female; mean [SD] age at baseline, 44.2 [14.5] years), 1340 first incident cancer cases were identified during follow-up, with the most prevalent being 459 breast cancers, 180 prostate cancers, 135 skin cancers, 99 colorectal cancers, 47 non-Hodgkin lymphomas, and 15 other lymphomas. High organic food scores were inversely associated with the overall risk of cancer (hazard ratio for quartile 4 vs quartile 1, 0.75; 95% CI, 0.63-0.88; P for trend = .001; absolute risk reduction, 0.6%; hazard ratio for a 5-point increase, 0.92; 95% CI, 0.88-0.96). Conclusions and Relevance: A higher frequency of organic food consumption was associated with a reduced risk of cancer. If these findings are confirmed, further research is necessary to determine the underlying factors involved in this association.

Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study.

BACKGROUND: Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS). How the consumption of foods with high/low FSAm-NPS relates to cancer risk has been studied in national/regional cohorts but has not been characterized in diverse European populations. METHODS AND FINDINGS: This prospective analysis included 471,495 adults from the European Prospective Investigation into Cancer and Nutrition (EPIC, 1992-2014, median follow-up: 15.3 y), among whom there were 49,794 incident cancer cases (main locations: breast, n = 12,063; prostate, n = 6,745; colon-rectum, n = 5,806). Usual food intakes were assessed with standardized country-specific diet assessment methods. The FSAm-NPS was calculated for each food/beverage using their 100-g content in energy, sugar, saturated fatty acid, sodium, fibres, proteins, and fruits/vegetables/legumes/nuts. The FSAm-NPS scores of all food items usually consumed by a participant were averaged to obtain the individual FSAm-NPS Dietary Index (DI) scores. Multi-adjusted Cox proportional hazards models were computed. A higher FSAm-NPS DI score, reflecting a lower nutritional quality of the food consumed, was associated with a higher risk of total cancer (HRQ5 versus Q1 = 1.07; 95% CI 1.03-1.10, P-trend < 0.001). Absolute cancer rates in those with high and low (quintiles 5 and 1) FSAm-NPS DI scores were 81.4 and 69.5 cases/10,000 person-years, respectively. Higher FSAm-NPS DI scores were specifically associated with higher risks of cancers of the colon-rectum, upper aerodigestive tract and stomach, lung for men, and liver and postmenopausal breast for women (all P < 0.05). The main study limitation is that it was based on an observational cohort using self-reported dietary data obtained through a single baseline food frequency questionnaire; thus, exposure misclassification and residual confounding cannot be ruled out. CONCLUSIONS: In this large multinational European cohort, the consumption of food products with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher risk of cancer. This supports the relevance of the FSAm-NPS as underlying nutrient profiling system for front-of-pack nutrition labels, as well as for other public health nutritional measures.