Serge Hercberg

Selenium and Prostate Cancer: Analysis of Individual Participant Data From Fifteen Prospective Studies

Background: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade. Methods: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided. Results: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, Pheterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, Ptrend < .001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, Pheterogeneity = .08). Conclusions: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation.

Abstract P5-12-02: B-vitamin intake from diet and supplements and breast cancer risk in middle-aged women: Results from the prospective NutriNet-Santé cohort

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 of them included quantitative assessment of supplemental intake. This prospective study aimed at investigating the associations between intakes of B-vitamins (dietary, supplemental, total) and breast cancer risk. 27,853 women aged ≥45y from the NutriNet-Sante cohort (2009-2016) were included, with a median follow-up time of 4.2 years. Dietary data were collected using repeated 24h 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. 462 incident breast cancers were diagnosed. Dietary (HR Q4vs.Q1 =0.74(0.55,0.99), P-trend=0.05), supplemental (HR Q4vs.Q1 =0.61(0.38,0.98), P-trend=0.05) and total (HR Q4vs.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 (HR per 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. Citation Format: Egnell M, Fassier P, Lecuyer L, Zelek L, Vasson M-P, Hercberg S, Latino-Martel P, Galan P, Deschasaux M, Touvier M. B-vitamin intake from diet and supplements and breast cancer risk in middle-aged women: Results from the prospective NutriNet-Sante cohort [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-12-02.

Abstract P1-02-01: 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 non-targeted 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 etiology of this complex disease. Methods: A prospective nested case-control study was set up in the SU.VI.MAX cohort, including 206 breast cancer cases diagnosed during a 13y follow-up, and 396 matched controls. Non-targeted 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 (OR T3vsT1 =0.37[0.23-0.61] for glycerol-derived compounds) to 0.04 (OR T3vsT1 =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 favorable 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. Citation Format: Lecuyer L, Victor Bala A, Deschasaux M, Bouchemal N, Nawfal Triba M, Vasson M-P, Rossary A, Demidem A, Galan P, Hercberg S, Partula V, Le Moyec L, Srour B, Fiolet T, Latino-Martel P, Kesse-Guyot E, Zelek L, Savarin P, Touvier M. NMR metabolomic signatures reveal predictive plasma metabolites associated with long-term risk of developing breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-02-01.

NMR metabolomic signatures reveal predictive plasma metabolites associated with long-termrisk of developing breast cancer

NMR metabolomic signatures reveal predictive plasma metabolites associated with long-term risk of developing breast cancer. IUNS 21st International Congress of NutritionBackground and objectives: The University of Southampton and International Malnutrition Task Force developed Malnutrition eLearning to reduce child mortality by Severe Acute Malnutrition (SAM) through training health professionals globally. Since made available in 2010, over 14,000 from 100+ countries used the course. To investigate its effectiveness, a 2-year evaluation study was conducted from 2015, face-to-face in Ghana and Central America (CA), and online in other countries.Methods: Using a mixed method approach, the study explored if and how Malnutrition eLearning supported knowledge gain and behavioural change (application of knowledge in clinical practice), and resulting clinical outcomes in the management of SAM. Assessments, questionnaires and interviews/focus groups were conducted with individual in-service and pre-service participants pre- and post-training, and 12 months of medical records data collection, observations and hospital personnel interviews were carried out from participating healthcare institutions.Results: Total 1,261 health professionals (Ghana:915, CA:142, other countries:201), and 10 hospitals and 2 community health centres in Ghana and 2 hospitals in CA participated in the study. 3,955 (pre:01/08/2014–31/07/2015) and 3,737 (post:01/08/2015– 31/07/2016) medical records of children (0-60 months) were collected from the hospitals, and summary data on malnutrition cases (pre:76, post:67) from community health centres. Individual participants scored significantly higher in the post assessment (mean difference(SD): 14.0(12.5), 95%CI(12.7, 15.2), p<0.001). 87% of in-service health professionals (102/117) applied their knowledge and changed clinical practice in screening, assessment, diagnosis and management of SAM. This group demonstrated retained knowledge 6-month after the training (mean difference from pre-assessment(SD): 12.7(11.7), 95%CI(10.4, 15.0),p<0.001). Significant increases (p<0.001) in recording malnutrition-markers, i.e. length/height and weight-for-length/ height z-score, and diagnosed SAM cases (pre: 491(12.4%), post: 810(21.7%)) were observed. Mortality by SAM was declined from 26(5.9%) to 14(1.9%) (p<0.001). The community centres initiated the management of SAM (pre:0/32, post:7/21).Conclusions: The results suggest that Malnutrition eLearning is effective in training the WHO guideline on the management of SAM. After a 2-day self-directed training with Malnutrition eLearning, the participants not only gained knowledge but were also able to apply the knowledge in their clinical practice, leading to significant impacts on clinical outcomes.Acknowledgement: This study was supported by the UK Department for International Development Nutrition Embedding Evaluation Programme, managed by PATH.This paper was presented at IUNS 21st International Congress of Nutrition, Buenos Aires, Argentina, 15-20 October. This is the peer-reviewed but unedited manuscript version of the following article: MARKEY, O. ...et al., 2017. Postprandial lipid responses after long-term intake of dairy products varying in fatty acid composition. Annals of Nutrition and Metabolism, 71 (Suppl 2), pp. 346 (DOI: 10.1159/000480486). The final, published version is available at https://doi.org/10.1159/000480486