title: Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort.
abstract: BACKGROUND
  Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity.
  
  
  OBJECTIVE
  This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer.
  
  
  METHODS
  In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for α-carotene, β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided.
  
  
  RESULTS
  In quintile 5 compared with quintile 1, α-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and β-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for β-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution).
  
  
  CONCLUSIONS
  Our results indicate that higher concentrations of plasma β-carotene and α-carotene are associated with lower breast cancer risk of ER- tumors.
authors.affiliation: Julius Center for Health Sciences and Primary Care and m.f.bakker-8@umcutrecht.nl.
authors.forename: Marije F
authors.initials: MF
authors.lastname: Bakker
authors.affiliation: Julius Center for Health Sciences and Primary Care and Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom;
authors.forename: Petra Hm
authors.initials: PH
authors.lastname: Peeters
authors.affiliation: Julius Center for Health Sciences and Primary Care and Division of Human Nutrition, Wageningen University, Wageningen, Netherlands;
authors.forename: Veronique M
authors.initials: VM
authors.lastname: Klaasen
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, Netherlands; Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom; National Institute for Public Health and the Environment, Bilthoven, Netherlands; Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia;
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.affiliation: National Institute for Public Health and the Environment, Bilthoven, Netherlands;
authors.forename: Eugene Hjm
authors.initials: EH
authors.lastname: Jansen
authors.affiliation: National Institute for Public Health and the Environment, Bilthoven, Netherlands;
authors.forename: Martine M
authors.initials: MM
authors.lastname: Ros
authors.affiliation: Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain;
authors.forename: Noémie
authors.initials: N
authors.lastname: Travier
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark;
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark;
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark;
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.affiliation: International Agency for Research on Cancer, Lyon, France;
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.affiliation: International Agency for Research on Cancer, Lyon, France;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.affiliation: International Agency for Research on Cancer, Lyon, France;
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.affiliation: Inserm, Centre for Research in Epidemiology and Population Health, U1018, Nutrition, Hormones and Women's Health Team, Villejuif, France; University Paris-Sud, UMRS 1018, Villejuif, France; IGR, Villejuif, France;
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.affiliation: Inserm, Centre for Research in Epidemiology and Population Health, U1018, Nutrition, Hormones and Women's Health Team, Villejuif, France; University Paris-Sud, UMRS 1018, Villejuif, France; IGR, Villejuif, France;
authors.forename: Florence
authors.initials: F
authors.lastname: Perquier
authors.affiliation: Inserm, Centre for Research in Epidemiology and Population Health, U1018, Nutrition, Hormones and Women's Health Team, Villejuif, France; University Paris-Sud, UMRS 1018, Villejuif, France; IGR, Villejuif, France;
authors.forename: Claire
authors.initials: C
authors.lastname: Cadeau
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany;
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany;
authors.forename: Krasimira
authors.initials: K
authors.lastname: Aleksandrova
authors.affiliation: German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany;
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.affiliation: German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany;
authors.forename: Tilman
authors.initials: T
authors.lastname: Kühn
authors.affiliation: WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece; Hellenic Health Foundation, Athens, Greece;
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece; Department of Epidemiology, Harvard School of Public Health, Boston, MA; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece;
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.affiliation: Hellenic Health Foundation, Athens, Greece; Department of Epidemiology, Harvard School of Public Health, Boston, MA; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece;
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom; Human Genetic Foundation (HuGeF), Turin, Italy;
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.affiliation: Dipartimento Di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy;
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy;
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.affiliation: Cancer Registry and Histopathology Unit, "Civic M.P.Arezzo" Hospital, ASP Ragusa, Italy;
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway; Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland;
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway;
authors.forename: Guri
authors.initials: G
authors.lastname: Skeie
authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway;
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.affiliation: Public Health Directorate, Asturias, Spain;
authors.forename: J Ramón
authors.initials: JR
authors.lastname: Quirós
authors.affiliation: Navarre Public Health Institute, Pamplona, Spain; CIBER de Epidemiology and Public Health (CIPERESP), Spain;
authors.forename: Eva
authors.initials: E
authors.lastname: Ardanaz
authors.affiliation: Consortium for Biomedical Research in Epidemiology and public Health (CIBER de Epidemiología y Salud Pública), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain; Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain;
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.affiliation: Consortium for Biomedical Research in Epidemiology and public Health (CIBER de Epidemiología y Salud Pública), Madrid, Spain; Public Health Division of Gipuzkoa, BioDonostia Research Institute, Health Department of Basque Region, San Sebastian, Spain;
authors.forename: Pilar
authors.initials: P
authors.lastname: Amiano
authors.affiliation: Consortium for Biomedical Research in Epidemiology and public Health (CIBER de Epidemiología y Salud Pública), Madrid, Spain; Andalusian School of Public Health, Granada, Spain;
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez
authors.affiliation: Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain;
authors.forename: Genevieve
authors.initials: G
authors.lastname: Buckland
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden;
authors.forename: Ulrika
authors.initials: U
authors.lastname: Ericson
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden;
authors.forename: Emily
authors.initials: E
authors.lastname: Sonestedt
authors.affiliation: International Agency for Research on Cancer, Lyon, France; Department of Biobank Research and.
authors.forename: Matthias
authors.initials: M
authors.lastname: Johansson
authors.affiliation: Department of Surgery, Umeå University, Umeå, Sweden;
authors.forename: Malin
authors.initials: M
authors.lastname: Sund
authors.affiliation: Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom;
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.affiliation: Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom;
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Key
authors.affiliation: University of Cambridge, Cambridge, United Kingdom; and.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Nick
authors.initials: N
authors.lastname: Wareham
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom;
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.affiliation: Julius Center for Health Sciences and Primary Care and.
authors.forename: Carla H
authors.initials: CH
authors.lastname: van Gils
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000032:analysis* / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000097:blood / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D002338:Carotenoids / Q000097:blood* / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D004032:Diet; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D017698:Postmenopause; D017697:Premenopause; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000378:metabolism; D012306:Risk; D024505:Tocopherols / Q000097:blood / Q000627:therapeutic use; D014801:Vitamin A / Q000097:blood / Q000627:therapeutic use; D019207:beta Carotene / Q000097:blood* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D019207:beta Carotene; D014801:Vitamin A; D002338:Carotenoids; C041635:alpha-carotene; D001205:Ascorbic Acid; D024505:Tocopherols
keywords: EPIC; antioxidants; breast cancer; carotenoids; plasma