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Circulating Folate and Vitamin B12 and Risk of Prostate Cancer: A Collaborative Analysis of Individual Participant Data from Six Cohorts Including 6875 Cases and 8104 Controls

Price AJ 1 , Travis RC 2 , Appleby PN 2 , Albanes D 3 , Barricarte Gurrea A 4 , Bjørge T 5 Show all authors , Bueno-de-Mesquita HB 6 , Chen C 7 , Donovan J 8 , Gislefoss R 9 , Goodman G 7 , Gunter M 10 , Hamdy FC 11 , Johansson M 12 , King IB 13 , Kühn T 14 , Männistö S 15 , Martin RM 16 , Meyer K 17 , Neal DE 18 , Neuhouser ML 7 , Nygård O 19 , Stattin P 20 , Tell GS 21 , Trichopoulou A 22 , Tumino R 23 , Ueland PM 24 , Ulvik A 17 , de Vogel S 21 , Vollset SE 25 , Weinstein SJ 3 , Key TJ 2 , Allen NE 26 , Endogenous Hormones, Nutritional Biomarkers, and Prostate Cancer Collaborative Group

Affiliations 

  • 1 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
  • 2 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK
  • 3 Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda MD, USA
  • 4 Navarra Public Health Institute, Pamplona, Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
  • 5 Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Cancer Registry of Norway, Oslo, Norway
  • 6 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
  • 7 Public Health Sciences Division, Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  • 8 School of Social and Community Medicine, University of Bristol, Bristol, UK
  • 9 Cancer Registry of Norway, Oslo, Norway; Institute of Population-based research, Montebello, Oslo, Norway
  • 10 Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK
  • 11 Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, UK
  • 12 International Agency for Research on Cancer, Lyon, France; Department of Biobank Research, Umeå University, Umeå, Sweden
  • 13 Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA
  • 14 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 15 Department of Health, National Institute for Health and Welfare, Helsinki, Finland
  • 16 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
  • 17 Bevital AS, Bergen, Norway
  • 18 Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK
  • 19 Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
  • 20 Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden
  • 21 Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
  • 22 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
  • 23 Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Ragusa, Italy
  • 24 Department of Clinical Science, University of Bergen, Bergen, Norway
  • 25 Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Norwegian Institute of Public Health, Bergen, Norway
  • 26 Clinical trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Clinical Medicine, University of Oxford, UK
Eur Urol, 2016 Dec;70(6):941-951.
PMID: 27061263 DOI: 10.1016/j.eururo.2016.03.029

Abstract

BACKGROUND: Folate and vitamin B12 are 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.

OBJECTIVE: To investigate the associations between circulating folate and vitamin B12 concentrations and risk of PCa overall and by disease stage and grade.

DESIGN, SETTING, AND PARTICIPANTS: 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 B12 were calculated using multivariable adjusted conditional logistic regression.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incident PCa and subtype by stage and grade.

RESULTS AND LIMITATIONS: Higher folate and vitamin B12 concentrations 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 B12 with risk by stage or grade of disease (pheterogeneity>0.05). Use of single blood-sample measurements of folate and B12 concentrations is a limitation.

CONCLUSIONS: 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.

PATIENT SUMMARY: 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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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