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Circulating Concentrations of Folate and Vitamin B₁₂ in Relation to Prostate Cancer Risk: Results from the European Prospective Investigation into Cancer and Nutrition Study

¹ Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden; ² Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, United Kingdom; ³ International Agency for Research on Cancer, Lyon, France; Departments of ⁴ Epidemiology & Biostatistics and ⁵ Urology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; ⁶ Department of Public Health and Primary Health Care, and ⁷ Institute of Medicine, LOCUS for Homocysteine and Related Vitamins, University of Bergen, Bergen, Norway; ⁸ Andalusian School of Public Health, Granada, Spain; ⁹ Public Health and Health Planning Directorate, Asturias, Spain; ¹⁰ Department of Epidemiology, Catalan Institute of Oncology, Barcelona, Spain; ¹¹ Public Health Department of Gipuzkoa, Gipuzkoa, Spain; ¹² Epidemiology Department, Murcia Health Council and CIBER en Epidemiología y Salud Pública (CIBERESP), Murcia, Spain; ¹³ Public Health Institute of Navarra, Pamplona and CIBER en Epidemiología y Salud Pública (CIBERESP), Pamplona, Spain; ¹⁴ Nutritional Epidemiology Unit, National Cancer Institute, Milan, Italy; ¹⁵ Molecular and Nutritional Epidemiology Unit, Scientific Institute of Tuscany, Florence, Italy; ¹⁶ CSPO and University of Turin, Turin, Italy; ¹⁷ Cancer Registry, Azienda Ospedaliera Civile M.P. Arezzo, Ragusa, Italy; ¹⁸ Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany; ¹⁹ German Institute of Human Nutrition, Potsdam-Rehbücke, Germany; ²⁰ Department of Hygiene, University of Athens Medical School, Athens, Greece; ²¹ Hellenic Health Foundation, Athens, Greece; ²² Department of Gerontology and ²³ MRC Dunn Human Nutrition Unit & MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; ²⁴ Nutritional Research, Umeå University Hospital, Umeå, Sweden; and ²⁵ Department of Epidemiology & Public Health, Imperial College, London, United Kingdom

Requests for reprints: Mattias Johansson, Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, 901 85 Umeå, Sweden. Phone: 46-90785-4849; Fax: 46-9012-5396. E-mail: Mattias.Johansson{at}oc.umu.se

Background: Determinants of one-carbon metabolism, such as folate and vitamin B₁₂, have been implicated in cancer development. Previous studies have not provided conclusive evidence for the importance of circulating concentrations of folate and vitamin B₁₂ in prostate cancer etiology. The aim of the present study was to investigate the relationship between prostate cancer risk and circulating concentrations of folate and vitamin B₁₂ in a large prospective cohort.

Methods: We analyzed circulating concentrations of folate and vitamin B₁₂ in 869 cases and 1,174 controls, individually matched on center, age, and date of recruitment, nested within the European Prospective Investigation into Cancer and Nutrition cohort. Relative risks (RR) for prostate cancer were estimated using conditional logistic regression models.

Results: Overall, no significant associations were observed for circulating concentrations of folate (P_trend = 0.62) or vitamin B₁₂ (P_trend = 0.21) with prostate cancer risk. RRs for a doubling in folate and vitamin B₁₂ concentrations were 1.03 [95% confidence interval (95% CI), 0.92-1.16] and 1.12 (95% CI, 0.94-1.35), respectively. In the subgroup of cases diagnosed with advanced stage prostate cancer, elevated concentrations of vitamin B₁₂ were associated with increased risk (RR for a doubling in concentration, 1.69; 95% CI, 1.05-2.72, P_trend = 0.03). No other subgroup analyses resulted in a statistically significant association.

Conclusion: This study does not provide strong support for an association between prostate cancer risk and circulating concentrations of folate or vitamin B₁₂. Elevated concentrations of vitamin B₁₂ may be associated with an increased risk for advanced stage prostate cancer, but this association requires examination in other large prospective studies. (Cancer Epidemiol Biomarkers Prev 2007;17(2):279–85)