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1. Biomarkers of mammographic density in premenopausal women.

Author

His M, Lajous M, Gómez-Flores-Ramos L, Monge A, Dossus L, Viallon V, Gicquiau A, Biessy C, Gunter MJ, and Rinaldi S

Subjects
Adult, Body Mass Index, Breast diagnostic imaging, Breast Neoplasms blood, Breast Neoplasms diagnostic imaging, Cholesterol blood, Cross-Sectional Studies, Female, Humans, Mammography, Metabolomics, Mexico, Middle Aged, Phosphatidylcholines blood, Risk Factors, Sphingomyelins blood, Biomarkers blood, Breast Density physiology, Premenopause
Abstract

Background: While mammographic density is one of the strongest risk factors for breast cancer, little is known about its determinants, especially in young women. We applied targeted metabolomics to identify circulating metabolites specifically associated with mammographic density in premenopausal women. Then, we aimed to identify potential correlates of these biomarkers to guide future research on potential modifiable determinants of mammographic density., Methods: A total of 132 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, hexose) were measured by tandem liquid chromatography/mass spectrometry in plasma samples from 573 premenopausal participants in the Mexican Teachers' Cohort. Associations between metabolites and percent mammographic density were assessed using linear regression models, adjusting for breast cancer risk factors and accounting for multiple tests. Mean concentrations of metabolites associated with percent mammographic density were estimated across levels of several lifestyle and metabolic factors., Results: Sphingomyelin (SM) C16:1 and phosphatidylcholine (PC) ae C30:2 were inversely associated with percent mammographic density after correction for multiple tests. Linear trends with percent mammographic density were observed for SM C16:1 only in women with body mass index (BMI) below the median (27.4) and for PC ae C30:2 in women with a BMI over the median. SM C16:1 and PC ae C30:2 concentrations were positively associated with cholesterol (total and HDL) and inversely associated with number of metabolic syndrome components., Conclusions: We identified new biomarkers associated with mammographic density in young women. The association of these biomarkers with mammographic density and metabolic parameters may provide new perspectives to support future preventive actions for breast cancer., (© 2021. The Author(s).)

Published
2021
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2. Prospective analysis of circulating metabolites and breast cancer in EPIC.

Author

His M, Viallon V, Dossus L, Gicquiau A, Achaintre D, Scalbert A, Ferrari P, Romieu I, Onland-Moret NC, Weiderpass E, Dahm CC, Overvad K, Olsen A, Tjønneland A, Fournier A, Rothwell JA, Severi G, Kühn T, Fortner RT, Boeing H, Trichopoulou A, Karakatsani A, Martimianaki G, Masala G, Sieri S, Tumino R, Vineis P, Panico S, van Gils CH, Nøst TH, Sandanger TM, Skeie G, Quirós JR, Agudo A, Sánchez MJ, Amiano P, Huerta JM, Ardanaz E, Schmidt JA, Travis RC, Riboli E, Tsilidis KK, Christakoudi S, Gunter MJ, and Rinaldi S

Subjects
Adult, Aged, Biomarkers analysis, Biomarkers metabolism, Breast Neoplasms diagnosis, Breast Neoplasms epidemiology, Case-Control Studies, Cohort Studies, Female, Humans, Incidence, Mass Spectrometry, Middle Aged, Prospective Studies, Risk Factors, Biomarkers blood, Breast Neoplasms blood, Metabolomics methods
Abstract

Background: Metabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk., Methods: A nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression., Results: Among women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70-0.90), asparagine (OR = 0.83 (0.74-0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76-0.90)), aa C36:3 (OR = 0.84 (0.77-0.93)), ae C34:2 (OR = 0.85 (0.78-0.94)), ae C36:2 (OR = 0.85 (0.78-0.88)), and ae C38:2 (OR = 0.84 (0.76-0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11-1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06-1.24)) and PC ae C36:3 (OR = 0.88 (0.82-0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity., Conclusions: These findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.

Published
2019
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3. Prospective associations between serum biomarkers of lipid metabolism and overall, breast and prostate cancer risk.

Author

His M, Zelek L, Deschasaux M, Pouchieu C, Kesse-Guyot E, Hercberg S, Galan P, Latino-Martel P, Blacher J, and Touvier M

Subjects
Adult, Aged, Apolipoprotein A-I blood, Apolipoproteins B blood, Breast Neoplasms epidemiology, Cholesterol, HDL blood, Cholesterol, LDL blood, Female, Follow-Up Studies, Humans, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Prostatic Neoplasms epidemiology, Risk Factors, Triglycerides blood, Biomarkers blood, Breast Neoplasms blood, Lipid Metabolism, Lipids blood, Prostatic Neoplasms blood
Abstract

Experimental studies provided evidence about mechanisms by which cholesterol, especially high density lipoprotein cholesterol (HDL-C), could influence carcinogenesis, notably through antioxidant and anti-inflammatory properties. However, prospective studies that investigated the associations between specific lipid metabolism biomarkers and cancer risk provided inconsistent results. The objective was to investigate the prospective associations between total cholesterol (T-C), HDL-C, low density lipoprotein cholesterol, apolipoproteins A1 (apoA1) and B, and triglycerides and overall, breast and prostate cancer risk. Analyses were performed on 7,557 subjects of the Supplémentation en Vitamines et Minéraux Antioxydants Study, a nationwide French cohort study. Biomarkers of lipid metabolism were measured at baseline and analyzed regarding the risk of first primary incident cancer (N = 514 cases diagnosed during follow-up, 1994-2007), using Cox proportional hazards models. T-C was inversely associated with overall (HR(1mmol/L increment) = 0.91, 95 % CI 0.82-1.00; P = 0.04) and breast (HR(1mmol/L increment) = 0.83, 95 % CI 0.69-0.99; P = 0.04) cancer risk. HDL-C was also inversely associated with overall (HR(1mmol/L increment) = 0.61, 95 % CI 0.46-0.82; P = 0.0008) and breast (HR(1mmol/L increment) = 0.48, 95 % CI 0.28-0.83; P = 0.009) cancer risk. Consistently, apoA1 was inversely associated with overall (HR(1g/L increment) = 0.56, 95 % CI 0.39-0.82; P = 0.003) and breast (HR(1g/L increment) = 0.36, 95 % CI 0.18-0.73; P = 0.004) cancer risk. This prospective study suggests that pre-diagnostic serum levels of T-C, HDL-C and ApoA1 are associated with decreased overall and breast cancer risk. The confirmation of a role of cholesterol components in cancer development, by further large prospective and experimental studies, may have important implications in terms of public health, since cholesterol is already crucial in cardiovascular prevention.

Published
2014
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4. Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort

Author

Matejcic, M., de Batlle, J., Ricci, C., Biessy, C., Perrier, F., Huybrechts, I., Weiderpass, E., Boutron-Ruault, M. C., Cadeau, C., His, M., Cox, D. G., Boeing, H., Fortner, R. T., Kaaks, R., Lagiou, P., Trichopoulou, A., Benetou, V., Tumino, R., Panico, S., Sieri, S., Palli, D., Ricceri, F., Bueno-de-Mesquita, H. Bas, Skeie, G., Amiano, P., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Quirós, J. R., Buckland, G., van Gils, C. H., Peeters, P. H., Key, T. J., Riboli, E., Gylling, B., Zeleniuch-Jacquotte, A., Gunter, M. J., Romieu, I., Chajès, V., Matejcic, M, de Batlle, J, Ricci, C, Biessy, C, Perrier, F, Huybrechts, I, Weiderpass, E, Boutron Ruault, M. C, Cadeau, C, His, M, Cox, D. G, Boeing, H, Fortner, R. T, Kaaks, R, Lagiou, P, Trichopoulou, A, Benetou, V, Tumino, R, Panico, Salvatore, Sieri, S, Palli, D, Ricceri, F, Bueno de Mesquita, H. B. A, Skeie, G, Amiano, P, Sánchez, M. J, Chirlaque, M. D, Barricarte, A, Quirós, J. R, Buckland, G, van Gils, C. H, Peeters, P. H, Key, T. J, Riboli, E, Gylling, B, Zeleniuch Jacquotte, A, Gunter, M. J, Romieu, I, Chajès, V., University Medical Center Utrecht, and Imperial College Trust

Subjects
hormone receptor status, Cancer Research, MTHFR polymorphism, Risk Factors, Neoplasms, Progesterone, Medicine(all), alcohol, plasma biomarker, Single Nucleotide, vitamin B12, Middle Aged, Multicenter Study, Europe, Vitamin B 12, Oncology, Female, breast cancer, folate, plasma biomarkers, Adult, Aged, Alcohol Drinking, Biomarkers, Breast Neoplasms, Case-Control Studies, Diet, Estrogens, Folic Acid, Folic Acid Deficiency, Follow-Up Studies, Genes, erbB-2, Humans, Life Style, Methylenetetrahydrofolate Reductase (NADPH2), Neoplasms, Hormone-Dependent, Polymorphism, Single Nucleotide, Vitamin B 12 Deficiency, Journal Article, Oncology & Carcinogenesis, Hormone-Dependent, Polymorphism, erbB-2, hormone receptor statu, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Genes, 1112 Oncology And Carcinogenesis
Abstract

This is the peer reviewed version of the following article: Matejcic, M., De Batlle, J., Ricci, C., Biessy, C., Perrier, F., Huybrechts, I., ... Chajès, V. (2017). Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort. International Journal of Cancer, 140(6), 1246-1259. https://doi.org/10.1002/ijc.30536, which has been published in final form at https://doi.org/10.1002/ijc.30536. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4‐Q1 = 1.26; 95% CI 1.00–1.58; Ptrend = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4‐Q1 = 1.29; 95% CI 1.02–1.62; Ptrend = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.

Published
2016

5. A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study.

Author

Chajès, V., Assi, N., Biessy, C., Ferrari, P., Rinaldi, S., Slimani, N., Lenoir, G. M., Baglietto, L., His, M., Boutron-Ruault, M. C., Trichopoulou, A., Lagiou, P., Katsoulis, M., Kaaks, R., Kühn, T., Panico, S., Pala, V., Masala, G., Bueno-de-Mesquita, H. B., and Peeters, P. H.

Subjects
*BREAST cancer, *BREAST cancer risk factors, *FATTY acids, *GAS chromatography, *PHOSPHOLIPIDS, *ESTROGEN receptors, *LIPID synthesis
Abstract

Background: Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting. Materials and methods: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours. Results: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend=0.0001, q value=0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend=0.002, q value=0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend=0.047], whereas no association was found for ER-positive tumours (P-heterogeneity=0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor. Conclusion: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk. [ABSTRACT FROM AUTHOR]

Published
2017
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6. Prospective analysis of circulating metabolites and breast cancer in EPIC

Author

José María Huerta, Salvatore Panico, Antonia Trichopoulou, Joseph A. Rothwell, Sabina Sieri, Anja Olsen, Christina C. Dahm, Ruth C. Travis, Audrey Gicquiau, Pilar Amiano, Elisabete Weiderpass, N. Charlotte Onland-Moret, Antonio Agudo, Anna Karakatsani, Isabelle Romieu, Paolo Vineis, Mathilde His, Elio Riboli, Marc J. Gunter, Guri Skeie, Tilman Kühn, Augustin Scalbert, Carla H. van Gils, Georgia Martimianaki, Therese Haugdahl Nøst, Anne Tjønneland, Heiner Boeing, Laure Dossus, Pietro Ferrari, Julie A. Schmidt, Rosario Tumino, Konstantinos K. Tsilidis, David Achaintre, Torkjel M. Sandanger, Agnès Fournier, Sofia Christakoudi, María José Sánchez, Vivian Viallon, Renée T. Fortner, Kim Overvad, Giovanna Masala, Sabina Rinaldi, J. Ramón Quirós, Gianluca Severi, Eva Ardanaz, [His,M, Viallon,V, Dossus,L, Gicquiau,A, Achaintre,D, Scalbert,A, Ferrari,P, Weiderpass,E, Gunter,MJ, Rinaldi,S] International Agency for Research on Cancer, Lyon, France. [Romieu,I] Centre for Research on Population Health, National Institute of Public Health, Cuernavaca, Mexico. [Onland-Moret,NC, van Gils,CH] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. [Dahm,CC, Overvad,K] Department of Public Health, Aarhus University, Aarhus, Denmark. [Overvad,K] Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. [Olsen,A, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Tjønneland,A] University of Copenhagen, Copenhagen, Denmark. [Fournier,A, Rothwell,JA, Severi,G] CESP, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France. [Fournier,A, Severi,G] Gustave Roussy, Villejuif, France. [Kühn,T, Fortner,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Trichopoulou,A, Karakatsani,A, Martimianaki,G] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, 'ATTIKON' University Hospital, Haidari, Greece. [Masala,G] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network – ISPRO, Florence, Italy. [Sieri,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Department, 'M.P.Arezzo'Hospital, ASP Ragusa, Ragusa, Italy. [Vineis,P] Italian Institute for Genomic Medicine (IIGM), Turin, Italy. [Vineis,P] MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. [Panico,S] Dipartimento di medicina clinica e chirurgia, Federico II University, Naples, Italy. [Nøst,TH, Sandanger,TM, Skeie,G] Department of Community Medicine, UiT the Arctic University of Norway, Tromso, Norway. [Skeie,G] Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Universidad de Granada, Granada, Spain. [Sánchez,MJ, Amiano,P, Huerta,JM, Ardanaz,E] CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Schmidt,JA, Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Riboli,E, Tsilidis,KK, Christakoudi,S] Department of Epidemiology and Biostatistics, Imperial College London, St Mary’s Campus, Norfolk Place, London, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Christakoudi,S] MRC Centre for Transplantation, King’s College London, Great Maze Pond, London, SE1 9RT, UK, This work was funded by the French National Cancer Institute (grant number 2015-166). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), European Research Council (ERC-2009-AdG 232997), and Nordforsk, Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra, and the CERCA Program (Generalitat de Catalunya) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).

Subjects
0301 basic medicine, Oncology, lcsh:Medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Mass Spectrometry, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Breast cancer, Information Science::Information Science::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Risk Factors, Estudios prospectivos, Prospective Studies, Prospective cohort study, 11 Medical and Health Sciences, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], education.field_of_study, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Incidence, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Metabolomics [Medical Subject Headings], General Medicine, Metabolómica, Middle Aged, metabolomics, 3. Good health, Research Design, 030220 oncology & carcinogenesis, Cohort, Neoplasias de la mama, Female, Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, Pharmacological [Medical Subject Headings], Cohort study, Research Article, prospective study, Adult, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Population, Breast Neoplasms, Càncer de mama, 03 medical and health sciences, breast cancer, Internal medicine, Cell Line, Tumor, General & Internal Medicine, medicine, Journal Article, Metabolomics, Humans, Prospective study, education, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, business.industry, lcsh:R, Case-control study, Cancer, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Odds ratio, medicine.disease, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Case-Control Studies, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Mass Spectrometry [Medical Subject Headings], Biomarkers
Abstract

BackgroundMetabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk.MethodsA nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression.ResultsAmong women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70–0.90), asparagine (OR = 0.83 (0.74–0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76–0.90)), aa C36:3 (OR = 0.84 (0.77–0.93)), ae C34:2 (OR = 0.85 (0.78–0.94)), ae C36:2 (OR = 0.85 (0.78–0.88)), and ae C38:2 (OR = 0.84 (0.76–0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11–1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06–1.24)) and PC ae C36:3 (OR = 0.88 (0.82–0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity.ConclusionsThese findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.

Published
2019

7. A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study

Author

Maria Wennberg, Antonia Trichopoulou, Isabelle Romieu, Laura Baglietto, Aurelio Barricarte, Marc J. Gunter, M. C. Boutron-Ruault, Nada Assi, Petra H.M. Peeters, Michail Katsoulis, Rudolf Kaaks, Veronique Chajes, Anette Hjartåker, Timothy J. Key, Pilar Amiano, R. Borgund Barnung, Kay-Tee Khaw, Mathilde His, C. H. van Gils, Melissa A. Merritt, Pagona Lagiou, Daniel Redondo-Sánchez, Virginia Menéndez, Carine Biessy, Gilbert M. Lenoir, Giovanna Masala, Elio Riboli, V. Pala, Tilman Kühn, K. Standahl Olsen, Nadia Slimani, S. Rinaldi, Pamela Ferrari, Hendrik B. Bueno-de-Mesquita, Salvatore Panico, Chajès, V, Assi, N, Biessy, C, Ferrari, P, Rinaldi, S, Slimani, N, Lenoir, G. M, Baglietto, L, His, M, Boutron ruault, M. C, Trichopoulou, A, Lagiou, P, Katsoulis, M, Kaaks, R, Kühn, T, Panico, Salvatore, Pala, V, Masala, G, Bueno de mesquita, H. B, Peeters, P. H, Van Gils, C, Hjartåker, A, Olsen, Standahl K, Barnung, Borgund R, Barricarte, A, Sanchez, D. Redondo, Menéndez, V, Amiano, P, Wennberg, M, Key, T, Khaw, K. T, Merritt, M. A, Riboli, E, Gunter, M. J, Romieu, I., and Imperial College Trust

Subjects
0301 basic medicine, diagnosis, neoplasms, epic study, Prospective evaluation, breast cancer risk, Institut Gustave Roussy, 0302 clinical medicine, Risk Factors, Receptors, Prospective Studies, Progesterone, Phospholipids, Tumor, Fatty Acids, Hematology, Middle Aged, Prognosis, estrogen receptor negative, Europe, Oncology, Receptors, Estrogen, 030220 oncology & carcinogenesis, language, biomarker, Epic study, epidemiology, Female, Receptors, Progesterone, biological markers, medicine.medical_specialty, Library science, Breast Neoplasms, fatty acids, Danish, 03 medical and health sciences, Breast cancer, breast cancer, Journal Article, medicine, Biomarkers, Tumor, Humans, Oncology & Carcinogenesis, phospholipids, plasma, breast, lipogenesis, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, business.industry, Public health, Biomarkers, EPIC, Epidemiology, Fatty acids, Case-Control Studies, Follow-Up Studies, Diet, Cancer, biomarkers, medicine.disease, Estrogen, language.human_language, Cancer registry, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, desaturation of blood, 030104 developmental biology, epic trial, heterogeneity, diet, business, 1112 Oncology And Carcinogenesis
Abstract

This is a pre-copyedited, author-produced version of an article accepted for publication in Annals of Oncology following peer review. The version of record Chajès, V., Assi, N., Biessy, C., Ferrari, P., Rinaldi, S., Slimani, N., ... Romieu, I. (2017). A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study. Annals of Oncology, 28(11), 2836-2842. https://doi.org/10.1093/annonc/mdx482, is available online at: https://doi.org/10.1093/annonc/mdx482. Background: Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting. Materials and methods: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours. Results: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4–Q1) 1.37; 95% confidence interval (CI), 1.14–1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n–7/16:0) [OR (Q4–Q1), 1.28; 95% C, 1.07–1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3–T1)=2.01; 95% CI, 1.03–3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor. Conclusion: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.

Published
2017

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