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.

Perineal suture practices. Are they up to date with the evidence based medicine data: A local experience into a university maternity?

OBJECTIVES: To investigate the prevalence of perineal suture techniques then to identify the factors influencing suturing technique choices. METHODS: Prospective, observational, monocentric study over 20 weeks in a university hospital. A personal questionnaire was completed by medical practitioners performing perineal sutures: years of experience, training attendance, suturing techniques usually used for degrees 1 and 2 tears/episiotomies. For each delivery with perineal tear/episiotomy, the professional answered on the type of suture performed and the reasons for choosing this technique. We distinguished discontinuous sutures (several stitches/continuous locking stitch) from continuous sutures (single thread, single continuous locking stitch). We evaluated the prevalence of the techniques used in our center as well as the factors associated with the choice of technique, then we described the characteristics of the professionals who responded to the survey and their suturing habits. RESULTS: Among the 401 perineal sutures, 45.4% of them were continuous (n = 182), discontinuous sutures were more performed. Discontinuous sutures were more common in 1st and 2nd degree tears. Residents/obstetricians performed significantly more continuous sutures than midwives. Whatever the type of suture technique used (continuous or discontinuous), professionals sutured in the way they felt most suitable to the degree of tearing/episiotomy. Fifty-one percent of midwives are trained in continuous technique, compared with 81% of residents/obstetricians. Midwives required training in 70% of cases and 64% of residents. CONCLUSIONS: It appears necessary to disseminate continuous suture techniques and to promote their training in order to improve our practices.

Fecal microbiome as determinant of the effect of diet on colorectal cancer risk: comparison of meat-based versus pesco-vegetarian diets (the MeaTIc study).

BACKGROUND: Convincing evidence suggests that the risk of colorectal cancer (CRC) is increased by the typical Western diet characterized by high consumption of red and processed meat. In addition, some epidemiological studies suggest a reduction in the risk of CRC associated with fish consumption. The role of the gut microbiome in this diet-associated risk is not well understood. METHODS/DESIGN: This is a randomized parallel open clinical trial comprising a total of 150 clinically healthy subjects randomly assigned to three groups: a meat-based diet of which 4 portions per week are red meat (1 portion = 150 g), 3 portions per week are processed meat (1 portion = 50 g), and 1 portion per week is poultry (1 portion = 150 g), for a total amount of 900 g per week of meat and derivatives; a meat-based diet supplemented with alpha-tocopherol; and a pesco-vegetarian diet excluding fresh and processed meat and poultry, but which includes 3 portions per week of fish for a total amount of 450 g per week. Each intervention will last 3 months. The three diets will be isocaloric and of three different sizes according to specific energy requirements. Anthropometric measurements, body composition, and blood and fecal samples will be obtained from each participant at the beginning and end of each intervention phase. The measure of the primary outcome will be the change from baseline in DNA damage induced by fecal water using the comet assay in a cellular model. Secondary outcome measures will be changes in the profile of fecal microbiomes, global fecal and urinary peroxidation markers, and neoplastic biomarkers. DISCUSSION: Although epidemiological data support the promoting role of meat and the possible protective role of fish in colon carcinogenesis, no study has directly compared dietary profiles characterized by the presence of these two food groups and the role of the gut microbiome in these diet-associated CRC risks. This study will test the effect of these dietary profiles on validated CRC risk biomarkers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03416777. Registered on 3 May 2018.

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.

Red Wine and Pomegranate Extracts Suppress Cured Meat Promotion of Colonic Mucin-Depleted Foci in Carcinogen-Induced Rats.

Processed meat intake is carcinogenic to humans. We have shown that intake of a workshop-made cured meat with erythorbate promotes colon carcinogenesis in rats. We speculated that polyphenols could inhibit this effect by limitation of endogenous lipid peroxidation and nitrosation. Polyphenol-rich plant extracts were added to the workshop-made cured meat and given for 14 days to rats and 100 days to azoxymethane-induced rats to evaluate the inhibition of preneoplastic lesions. Colons of 100-d study were scored for precancerous lesions (mucin-depleted foci, MDF), and biochemical end points of peroxidation and nitrosation were measured in urinary and fecal samples. In comparison with cured meat-fed rats, dried red wine, pomegranate extract, α-tocopherol added at one dose to cured meat and withdrawal of erythorbate significantly decreased the number of MDF per colon (but white grape and rosemary extracts did not). This protection was associated with the full suppression of fecal excretion of nitrosyl iron, suggesting that this nitroso compound might be a promoter of carcinogenesis. At optimized concentrations, the incorporation of these plant extracts in cured meat might reduce the risk of colorectal cancer associated with processed meat consumption.

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.

Alcoholic beverages, obesity, physical activity and other nutritional factors, and cancer risk: A review of the evidence.

PURPOSE: Prevention is a priority in the fight against cancers, especially nutritional prevention. To update the levels of evidence of relationships between 10 nutritional factors and cancer risk, the scientific literature published from 2006 to 2014 was reviewed by an expert group. METHODS: Data from 133 meta-analyses, pooled analyses or intervention trials were examined. Nearly 150 relationships between nutritional factors and cancer at various sites were evaluated. RESULTS: According to the evidence graded as convincing or probable, these factors were divided in two groups. Factors which increase the risk of cancer are alcoholic beverages, overweight and obesity, red meat and processed meat, salt and salted foods and beta-carotene supplements. Factors which decrease the risk of cancer are physical activity, fruits and vegetables, dietary fiber, dairy products and breastfeeding. CONCLUSION: Three main nutritional objectives should be attained to improve cancer prevention: to reduce alcoholic beverages consumption, to have a balanced and diversified diet and to be physically active.

Bisphenol a and its chlorinated derivatives in human colostrum.

The health effects related to bisphenol A (BPA) and its exposure sources have undergone extensive investigation, but no consensus has been reached. Hitherto, the major source of human BPA exposure considered in the literature remains food-contact material. However, the chlorine present in drinking water may react with BPA to form chlorinated derivatives (ClxBPA), which have indeed been shown to have a heightened level of estrogenic activity. In this study, we have evaluated colostrum concentrations of BPA and ClxBPA in order to confirm our hypothesis according to which BPA water contamination leads to ClxBPA human exposure. BPA and its ClxBPA were assessed through online solid-phase extraction coupled to ultra high-performance liquid chromatography tandem mass spectrometry (SPE-UPLC-MS/MS) using the isotope dilution method in the colostrums of 21 women who had completed a water exposure questionnaire. BPA was detected in 19 colostrums and its ClxBPA in 21 colostrums. Mean concentrations were 1.87 ± 1.38 ng mL(-1) (n = 19) for BPA, 1.87 ± 1.23 ng mL(-1) (n = 7) and 1.56 ± 0.74 (n = 18) ng mL(-1) for 2,2'-Cl2BPA and 2,6-Cl2BPA, respectively, and 0.68 ng mL(-1) (n = 1) for trichloro-BPA. These findings confirm our hypothesis that ClxBPA should be taken into account in human health risk assessment.

Calcium carbonate suppresses haem toxicity markers without calcium phosphate side effects on colon carcinogenesis.

Red meat intake is associated with an increased risk of colorectal cancer. We have previously shown that haemin, Hb and red meat promote carcinogen-induced preneoplastic lesions, aberrant crypt foci (ACF), in the colon of rats. We have also shown that dietary calcium phosphate inhibits haemin-induced promotion and normalises faecal lipoperoxides and cytotoxicity. Unexpectedly, high-calcium phosphate control diet-fed rats had more preneoplastic lesions in the colon than low-Ca control diet-fed rats. The present study was designed to find a Ca supplementation with no adverse effect, by testing several doses and types of Ca salts. One in vitro study and two short-term studies in rats identified calcium carbonate as the most effective Ca salt to bind haem in vitro and to decrease faecal biomarkers previously associated with increased carcinogenesis: faecal water cytotoxicity and thiobarbituric acid-reactive substances. A long-term carcinogenesis study in dimethylhydrazine-injected rats demonstrated that a diet containing 100 µmol/g calcium carbonate did not promote ACF, in contrast with a previously tested calcium phosphate diet. The results suggest that calcium carbonate, and not calcium phosphate, should be used to reduce haem-associated colorectal cancer risk in meat eaters. They support the concept that the nature of the associated anion to a protective metal ion is important for chemoprevention.

Beef meat promotion of dimethylhydrazine-induced colorectal carcinogenesis biomarkers is suppressed by dietary calcium.

Red meat consumption is associated with increased risk of colorectal cancer. We have previously shown that haemin, Hb and red meat promote carcinogen-induced preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF) in rats. We have also shown that dietary Ca, antioxidant mix and olive oil inhibit haemin-induced ACF promotion, and normalize faecal lipoperoxides and cytotoxicity. Here we tested if these strategies are effective also against red meat promotion in dimethylhydrazine-induced rats. Three diets with 60 % beef meat were supplemented with calcium phosphate (31 g/kg), antioxidant agents (rutin and butylated hydroxyanisole, 0.05 % each) and olive oil (5 %). ACF, MDF, faecal water cytotoxicity, thiobarbituric acid reactive substances (TBARS) and urinary 1,4-dihydroxynonane mercapturic acid (DHN-MA) were measured. Beef meat diet increased the number of ACF (+30 %) and MDF (+100 %) (P < 0.001), which confirms our previous findings. Promotion was associated with increased faecal water TBARs ( x 4) and cytotoxicity ( x 2), and urinary DHN-MA excretion ( x 15). Ca fully inhibited beef meat-induced ACF and MDF promotion, and normalized faecal TBARS and cytotoxicity, but did not reduce urinary DHN-MA. Unexpectedly, high-calcium control diet-fed rats had more MDF and ACF in the colon than low-Ca control diet-fed rats. Antioxidant mix and olive oil did not normalize beef meat promotion nor biochemical factors. The results confirm that haem causes promotion of colon carcinogenesis by red meat. They suggest that Ca can reduce colorectal cancer risk in meat-eaters. The results support the concept that toxicity associated with the excess of a useful nutrient may be prevented by another nutrient.

New marker of colon cancer risk associated with heme intake: 1,4-dihydroxynonane mercapturic acid.

BACKGROUND: Red meat consumption is associated with an increased risk of colon cancer. Animal studies show that heme, found in red meat, promotes preneoplastic lesions in the colon, probably due to the oxidative properties of this compound. End products of lipid peroxidation, such as 4-hydroxynonenal metabolites or 8-iso-prostaglandin-F(2)alpha (8-iso-PGF(2)alpha), could reflect this oxidative process and could be used as biomarkers of colon cancer risk associated with heme intake. METHODS: We measured urinary excretion of 8-iso-PGF(2)alpha and 1,4-dihydroxynonane mercapturic acid (DHN-MA), the major urinary metabolite of 4-hydroxynonenal, in three studies. In a short-term and a carcinogenesis long-term animal study, we fed rats four different diets (control, chicken, beef, and blood sausage as a high heme diet). In a randomized crossover human study, four different diets were fed (a 60 g/d red meat baseline diet, 120 g/d red meat, baseline diet supplemented with heme iron, and baseline diet supplemented with non-heme iron). RESULTS: DHN-MA excretion increased dramatically in rats fed high heme diets, and the excretion paralleled the number of preneoplastic lesions in azoxymethane initiated rats (P < 0.0001). In the human study, the heme supplemented diet resulted in a 2-fold increase in DHN-MA (P < 0.001). Urinary 8-iso-PGF(2)alpha increased moderately in rats fed a high heme diet (P < 0.0001), but not in humans. CONCLUSION: Urinary DHN-MA is a useful noninvasive biomarker for determining the risk of preneoplastic lesions associated with heme iron consumption and should be further investigated as a potential biomarker of colon cancer risk.

Beef meat and blood sausage promote the formation of azoxymethane-induced mucin-depleted foci and aberrant crypt foci in rat colons.

Red meat intake is associated with colon cancer risk. Puzzlingly, meat does not promote carcinogenesis in rat studies. However, we demonstrated previously that dietary heme promotes aberrant crypt foci (ACF) formation in rats given a low-calcium diet. Here, we tested the hypothesis that heme-rich meats promote colon carcinogenesis in rats treated with azoxymethane and fed low-calcium diets (0.8 g/kg). Three meat-based diets were formulated to contain varying concentrations of heme by the addition of raw chicken (low heme), beef (medium heme), or black pudding (blood sausage; high heme). The no-heme control diet was supplemented with ferric citrate and the heme control diet with hemoglobin to match iron and heme concentrations in the beef diet, respectively. After 100 d, colons were scored for ACF and mucin-depleted foci (MDF). Fecal water was assayed for lipoperoxides and cytotoxicity. Only diets with heme promoted the formation of MDF, but all meat diets promoted ACF formation. The number of MDF/colon was 0.55 +/- 0.68 in controls, but 1.2 +/- 0.6 (P = 0.13), 1.9 +/- 1.4 (P < 0.01), and 3.0 +/- 1.2 (P < 0.001) in chicken-, beef-, and black pudding-fed rats. MDF promotion by the high-heme black pudding diet was greater than that by the medium-heme beef diet. The number of ACF/colon was 72 +/- 16 in controls, but 91 +/- 18, 100 +/- 13, and 103 +/- 14 in chicken-, beef-, and black pudding-fed rats (all P < 0.001). ACF and MDF did not differ between rats fed the beef diet and those fed the heme control diet. MDF promotion was correlated with high fecal water lipoperoxides and cytotoxicity (r = 0.65, P < 0.01). This is the first study to show the promotion of experimental carcinogenesis by dietary meat and the association with heme intake.

Meat and cancer: haemoglobin and haemin in a low-calcium diet promote colorectal carcinogenesis at the aberrant crypt stage in rats.

High intake of red meat, but not of white meat, is associated with an increased risk of colon cancer. However, red meat does not promote cancer in rodents. Haemin, added to low-calcium diets, increases colonic proliferation, and haemoglobin, added to high-fat diets, increases the colon tumour incidence in rats, an effect possibly due to peroxyl radicals. We thus speculated that haem might be the promoting agent in meat, and that prevention strategies could use calcium and antioxidants. These hypotheses were tested in rats at the aberrant crypt foci (ACF) stage at 100 days. F344 rats (n = 124) were given an injection of azoxymethane and were then randomized to 11 groups fed with low-calcium (20 micro mol/g) AIN76-based diets, containing 5% safflower oil. Haemin (0.25, 0.5 and 1.5 micro mol/g) or haemoglobin (1.5 and 3 micro mol haem/g) was added to five experimental diets, compared with a control diet without haem. Three other high-haemin diets (1.5 micro mol/g) were supplemented with calcium (250 micro mol/g), antioxidant butylated hydroxyanisole and rutin (0.05% each), and olive oil, which replaced safflower oil. Faecal water was assayed for lipid peroxidation by thiobarbituric acid reactive substances (TBARs) test, and for cytolytic activity. Haemin strikingly increased the ACF size, dose-dependently, from 2.6 to 11.4 crypts/ACF (all P < 0.001). The high-haemin diet also increased the number of ACF per colon (P < 0.001). Promotion was associated with increased faecal water TBARs and cytotoxicity. Calcium, olive oil and antioxidants each inhibited the haemin-induced ACF promotion, and normalized the faecal TBARs and cytotoxicity. The haemoglobin diets increased the number of ACF and faecal TBARs, but not the ACF size or the faecal cytotoxicity. In conclusion, dietary haemin is the most potent known ACF promoter. Haemoglobin is also a potent promoter of colorectal carcinogenesis. The results suggest that myoglobin in red meat could promote colon cancer. Diets high in calcium, or in oxidation-resistant fats, may prevent the possible cancer-promoting effect of red meat.

Point: From animal models to prevention of colon cancer. Systematic review of chemoprevention in min mice and choice of the model system.

The Apc(Min/+) mouse model and the azoxymethane (AOM) rat model are the main animal models used to study the effect of dietary agents on colorectal cancer. We reviewed recently the potency of chemopreventive agents in the AOM rat model (D. E. Corpet and S. Tache, Nutr. Cancer, 43: 1-21, 2002). Here we add the results of a systematic review of the effect of dietary and chemopreventive agents on the tumor yield in Min mice. The review is based on the results of 179 studies from 71 articles and is displayed also on the internet http://corpet.net/min.(2) We compared the efficacy of agents in the Min mouse model and the AOM rat model, and found that they were correlated (r = 0.66; P < 0.001), although some agents that afford strong protection in the AOM rat and the Min mouse small bowel increase the tumor yield in the large bowel of mutant mice. The agents included piroxicam, sulindac, celecoxib, difluoromethylornithine, and polyethylene glycol. The reason for this discrepancy is not known. We also compare the results of rodent studies with those of clinical intervention studies of polyp recurrence. We found that the effect of most of the agents tested was consistent across the animal and clinical models. Our point is thus: rodent models can provide guidance in the selection of prevention approaches to human colon cancer, in particular they suggest that polyethylene glycol, hesperidin, protease inhibitor, sphingomyelin, physical exercise, epidermal growth factor receptor kinase inhibitor, (+)-catechin, resveratrol, fish oil, curcumin, caffeate, and thiosulfonate are likely important preventive agents.