title: Circulating Folate and Vitamin B12and Risk of Prostate Cancer: A Collaborative Analysis of Individual Participant Data from Six Cohorts Including 6875 Cases and 8104 Controls.
abstract: Folate and vitamin B12are essential for maintaining DNA integrity and may influence prostate cancer (PCa) risk, but the association with clinically relevant, advanced stage, and high-grade disease is unclear.
  
  
  
  To investigate the associations between circulating folate and vitamin B12concentrations and risk of PCa overall and by disease stage and grade.
  
  
  
  A study was performed with a nested case-control design based on individual participant data from six cohort studies including 6875 cases and 8104 controls; blood collection from 1981 to 2008, and an average follow-up of 8.9 yr (standard deviation 7.3). Odds ratios (ORs) of incident PCa by study-specific fifths of circulating folate and vitamin B12were calculated using multivariable adjusted conditional logistic regression.
  
  
  
  Incident PCa and subtype by stage and grade.
  
  
  
  Higher folate and vitamin B12concentrations were associated with a small increase in risk of PCa (ORs for the top vs bottom fifths were 1.13 [95% confidence interval (CI), 1.02-1.26], ptrend=0.018, for folate and 1.12 [95% CI, 1.01-1.25], ptrend=0.017, for vitamin B12), with no evidence of heterogeneity between studies. The association with folate varied by tumour grade (pheterogeneity<0.001); higher folate concentration was associated with an elevated risk of high-grade disease (OR for the top vs bottom fifth: 2.30 [95% CI, 1.28-4.12]; ptrend=0.001), with no association for low-grade disease. There was no evidence of heterogeneity in the association of folate with risk by stage or of vitamin B12with risk by stage or grade of disease (pheterogeneity>0.05). Use of single blood-sample measurements of folate and B12concentrations is a limitation.
  
  
  
  The association between higher folate concentration and risk of high-grade disease, not evident for low-grade disease, suggests a possible role for folate in the progression of clinically relevant PCa and warrants further investigation.
  
  
  
  Folate, a vitamin obtained from foods and supplements, is important for maintaining cell health. In this study, however, men with higher blood folate levels were at greater risk of high-grade (more aggressive) prostate cancer compared with men with lower folate levels. Further research is needed to investigate the possible role of folate in the progression of this disease.
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK; London School of Hygiene and Tropical Medicine, London, UK. Electronic address: alison.price@ceu.ox.ac.uk.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Price
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Appleby
authors.affiliation: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA.
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.affiliation: Navarra Public Health Institute, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte Gurrea
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Cancer Registry of Norway, Oslo, Norway.
authors.forename: Tone
authors.initials: T
authors.lastname: Bjørge
authors.affiliation: Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands; Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK; Department of Social and 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: Public Health Sciences Division, Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Jenny
authors.initials: J
authors.lastname: Donovan
authors.affiliation: Cancer Registry of Norway, Oslo, Norway; Institute of Population-based research, Montebello, Oslo, Norway.
authors.forename: Randi
authors.initials: R
authors.lastname: Gislefoss
authors.affiliation: Public Health Sciences Division, Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Goodman
authors.affiliation: Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Gunter
authors.affiliation: Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.affiliation: International Agency for Research on Cancer, Lyon, France; Department of Biobank Research, Umeå University, Umeå, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Johansson
authors.affiliation: Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Irena B
authors.initials: IB
authors.lastname: King
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Kühn
authors.affiliation: Department of Health, 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, UK; Medical Research Council/University of Bristol Integrative Epidemiology Unit, University of Bristol, Bristol, UK; National Institute for Health Research, Bristol Biomedical Research Unit in Nutrition, Bristol, UK.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.affiliation: Bevital AS, Bergen, Norway.
authors.forename: Klaus
authors.initials: K
authors.lastname: Meyer
authors.affiliation: Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.affiliation: Public Health Sciences Division, Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Marian L
authors.initials: ML
authors.lastname: Neuhouser
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
authors.forename: Ottar
authors.initials: O
authors.lastname: Nygård
authors.affiliation: Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
authors.forename: Par
authors.initials: P
authors.lastname: Stattin
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: Grethe S
authors.initials: GS
authors.lastname: Tell
authors.affiliation: WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens, Greece; Hellenic Health Foundation, Athens, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.affiliation: Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Ragusa, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.affiliation: Bevital AS, Bergen, Norway.
authors.forename: Arve
authors.initials: A
authors.lastname: Ulvik
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: Stefan
authors.initials: S
authors.lastname: de Vogel
authors.affiliation: Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Norwegian Institute of Public Health, Bergen, Norway.
authors.forename: Stein Emil
authors.initials: SE
authors.lastname: Vollset
authors.affiliation: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.affiliation: Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Key
authors.affiliation: Clinical trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Clinical Medicine, University of Oxford, UK.
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D005492:Folic Acid / Q000097:blood*; D006590:Hexetidine; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011471:Prostatic Neoplasms / Q000097:blood* / Q000453:epidemiology; D012306:Risk; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D006590:Hexetidine; D005492:Folic Acid; D014805:Vitamin B 12
keywords: Folate; High grade; Pooled data meta-analysis; Prospective cohort; Prostate cancer; Vitamin B(12)