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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.

By: Alison J Price, Ruth C Travis, Paul N Appleby, Demetrius Albanes, Aurelio Barricarte Gurrea, Tone Bjørge, H Bas Bueno-de-Mesquita, Chu Chen, Jenny Donovan, Randi Gislefoss, Gary Goodman, Marc Gunter, Freddie C Hamdy, Mattias Johansson, Irena B King, Tilman Kühn, Satu Männistö, Richard M Martin, Klaus Meyer, David E Neal, Marian L Neuhouser, Ottar Nygård, Par Stattin, Grethe S Tell, Antonia Trichopoulou, Rosario Tumino, Per Magne Ueland, Arve Ulvik, Stefan de Vogel, Stein Emil Vollset, Stephanie J Weinstein, Timothy J Key, Naomi E Allen,

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.
2015-11-18; 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,

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

Incident PCa and subtype by stage and grade.

Results

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

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.