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 lowgrade 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 highgrade 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.
| Original language | Undefined/Unknown |
|---|---|
| Pages (from-to) | 941-951 |
| Number of pages | 11 |
| Journal | European Urology |
| Volume | 70 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2016 |
Access to Document
- 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
© 2016 The Authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.