title: Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies.
abstract: BACKGROUND
  Individual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease.
  
  
  OBJECTIVE
  The objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, α-tocopherol, and γ-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors.
  
  
  METHODS
  Principal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets.
  
  
  RESULTS
  Data were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest compared with the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For α-tocopherol, the OR for the highest compared with the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). γ-Tocopherol was not associated with risk.
  
  
  CONCLUSIONS
  Overall prostate cancer risk was positively associated with retinol and inversely associated with α-tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and α-tocopherol. Whether these associations reflect causal relations is unclear.
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, tim.key@ceu.ox.ac.uk.
authors.forename: Timothy J
authors.identifier: http://orcid.org/0000-0003-2294-307X
authors.initials: TJ
authors.lastname: Key
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Appleby
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health.
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.affiliation: Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, MD;
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.affiliation: Department of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC;
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Alberg
authors.affiliation: Navarre Public Health Institute, Pamplona, Spain, and Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública), Spain;
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.affiliation: Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, MD;
authors.forename: Amanda
authors.initials: A
authors.lastname: Black
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany;
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, Netherlands; School of Public Health, Imperial College, London, United Kingdom;
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.affiliation: Departments of Epidemiology & Biostatistics and Urology, University of California, San Francisco, San Francisco, CA;
authors.forename: June M
authors.initials: JM
authors.lastname: Chan
authors.affiliation: Public Health Sciences Division, Program in Epidemiology.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, MD;
authors.forename: Michael B
authors.initials: MB
authors.lastname: Cook
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom;
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Donovan
authors.affiliation: Sorbonne Paris Cité Epidemiology and Biostatistics Research Center, Nutritional Epidemiology Research Team (Nutritional Epidemiology Research Team), Inserm U1153, Inra U1125, Cnam, University Paris 13, University Paris 5, University Paris 7, Bobigny, France;
authors.forename: Pilar
authors.initials: P
authors.lastname: Galan
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom;
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gilbert
authors.affiliation: Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia;
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.affiliation: Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA;
authors.forename: Edward
authors.initials: E
authors.lastname: Giovannucci
authors.affiliation: Departments of Epidemiology and Environmental Health, University of Washington, Seattle, WA;
authors.forename: Gary E
authors.initials: GE
authors.lastname: Goodman
authors.affiliation: SWOG Statistical Center.
authors.forename: Phyllis J
authors.initials: PJ
authors.lastname: Goodman
authors.affiliation: School of Public Health, Imperial College, London, United Kingdom;
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.affiliation: Department of Surgery, and.
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland;
authors.forename: Markku
authors.initials: M
authors.lastname: Heliövaara
authors.affiliation: Prevention and Research Center Mercy Medical Center, Baltimore, MD;
authors.forename: Kathy J
authors.initials: KJ
authors.lastname: Helzlsouer
authors.affiliation: Keck School of Medicine, University of Southern California, Los Angeles, CA;
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.affiliation: Sorbonne Paris Cité Epidemiology and Biostatistics Research Center, Nutritional Epidemiology Research Team (Nutritional Epidemiology Research Team), Inserm U1153, Inra U1125, Cnam, University Paris 13, University Paris 5, University Paris 7, Bobigny, France;
authors.forename: Serge
authors.initials: S
authors.lastname: Hercberg
authors.affiliation: George W Comstock Center for Public Health Research and Prevention, Hagerstown, MD;
authors.forename: Judy
authors.initials: J
authors.lastname: Hoffman-Bolton
authors.affiliation: Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, MD;
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
authors.affiliation: International Agency for Research on Cancer, Lyon, France; Department for Biobank Research, Umeå University, Umeå, Sweden;
authors.forename: Mattias
authors.initials: M
authors.lastname: Johansson
authors.affiliation: Department of Public Health and Primary Care and.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: Public Health Sciences Core Laboratories, Department of Internal Medicine, University of New Mexico, Albuquerque, NM.
authors.forename: Irena B
authors.initials: IB
authors.lastname: King
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland;
authors.forename: Paul
authors.initials: P
authors.lastname: Knekt
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI;
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.affiliation: University of Hawaii Cancer Center, Honolulu, HI;
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland;
authors.forename: Satu
authors.initials: S
authors.lastname: Männistö
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom; Medical Research Council/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; National Institute for Health Research, Bristol Biomedical Research Unit in Nutrition, Bristol, United Kingdom;
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.affiliation: Department of Community Medicine, Faculty of Medicine, University of Oslo and Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway;
authors.forename: Haakon E
authors.initials: HE
authors.lastname: Meyer
authors.affiliation: Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, MD;
authors.forename: Alison M
authors.initials: AM
authors.lastname: Mondul
authors.affiliation: Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, MD;
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Moy
authors.affiliation: Department of Oncology, University of Cambridge, Cambridge, United Kingdom;
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.affiliation: Division of Public Health Sciences, and.
authors.forename: Marian L
authors.initials: ML
authors.lastname: Neuhouser
authors.affiliation: Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy;
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.affiliation: Department of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD;
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Platz
authors.affiliation: Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia;
authors.forename: Camille
authors.initials: C
authors.lastname: Pouchieu
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland;
authors.forename: Harri
authors.initials: H
authors.lastname: Rissanen
authors.affiliation: Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA;
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Schenk
authors.affiliation: Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, Australia;
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA;
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.affiliation: Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark;
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.affiliation: Sorbonne Paris Cité Epidemiology and Biostatistics Research Center, Nutritional Epidemiology Research Team (Nutritional Epidemiology Research Team), Inserm U1153, Inra U1125, Cnam, University Paris 13, University Paris 5, University Paris 7, Bobigny, France;
authors.forename: Mathilde
authors.initials: M
authors.lastname: Touvier
authors.affiliation: Hellenic Health Foundation and Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece and.
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, MD;
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.affiliation: Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, MD;
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.affiliation: Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, MD;
authors.forename: Cindy Ke
authors.initials: CK
authors.lastname: Zhou
authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom;
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002338:Carotenoids / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D006801:Humans; D000077276:Lycopene; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D064887:Observational Studies as Topic; D011446:Prospective Studies; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000473:pathology; D012307:Risk Factors; D014801:Vitamin A / Q000097:blood*; D024502:alpha-Tocopherol / Q000097:blood*
chemical_list: D015415:Biomarkers; D014801:Vitamin A; D002338:Carotenoids; D024502:alpha-Tocopherol; D000077276:Lycopene
keywords: biomarkers; carotenoids; nested case-control study; pooled analysis; prostate cancer; retinol; tocopherols; vitamin A; vitamin E