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, AJORCID logo; Travis, RC; Appleby, PN; Albanes, D; Barricarte Gurrea, A; Bjørge, T; Bueno-de-Mesquita, HB; Chen, C; Donovan, J; Gislefoss, R; +24 more...Goodman, G; Gunter, M; Hamdy, FC; Johansson, M; King, IB; Kühn, T; Männistö, S; Martin, RM; Meyer, K; Neal, DE; Neuhouser, ML; Nygård, O; Stattin, P; Tell, GS; Trichopoulou, A; Tumino, R; Ueland, PM; Ulvik, A; de Vogel, S; Vollset, SE; Weinstein, SJ; Key, TJ; Allen, NE; Endogenous Hormones, Nutritional Biomarkers, and Prostate Cancer and (2016) 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. European urology, 70 (6). pp. 941-951. ISSN 0302-2838 DOI: 10.1016/j.eururo.2016.03.029
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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.


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