Research papers: Prostate CancerPolymorphisms of methylenetetrahydrofolate reductase and the risk of prostate cancer: a nested case–control studyVan Guelpen, Bethany R.a; Wirén, Sara M.b; Bergh, Anders R.J.a; Hallmans, Göranc; Stattin, Pär E.b; Hultdin, Johand Author Information Departments of aMedical Biosciences, Pathology bSurgery and Perioperative Sciences, Urology and Andrology cPublic Health and Clinical Medicine, Nutrition Research dMedical Biosciences, Clinical Chemistry, Umeå University Hospital, Sweden Correspondence to Dr Johan Hultdin, Department of Medical Biosciences, Clinical Chemistry, Umeå University Hospital, SE-901 85, Umeå, Sweden Tel: +0046 90 785 1260; fax: +0046 90 785 2829; e-mail: [email protected] Received 4 January 2005 Accepted 9 June 2005 European Journal of Cancer Prevention 15(1):p 46-50, February 2006. | DOI: 10.1097/01.cej.0000186640.19872.4d Buy Metrics Abstract It has been proposed that folate and polymorphisms of the enzyme methylenetetrahydrofolate reductase (MTHFR), which regulates influx of folate from DNA synthesis and repair to methylation reactions, are involved in the aetiology of cancer. To relate the MTHFR 677C→T and 1298A→C polymorphisms to the risk of prostate cancer, taking into consideration prospective plasma levels of folate, vitamin B12 and homocysteine. The design was a case–control study of 223 prostate cancer cases and 435 matched controls nested within the population-based Northern Sweden Health and Disease Cohort. Neither the MTHFR 677C→T nor the MTHFR 1298A→C polymorphism was statistically significantly associated with the risk of prostate cancer in univariate analysis by conditional logistic regression. After adjustment for MTHFR 1298A→C, plasma folate, vitamin B12, homocysteine, body mass index and smoking, the odds ratios were, for the 677 CT genotype, 1.52 [95% confidence interval (CI) 1.02–2.26], and for TT, 0.91 (95% CI 0.41–2.04). Our previously reported observation of a possible increase in the risk of prostate cancer at high plasma folate levels was attributable in this study to subjects having the MTHFR 677C→T polymorphism. We found that the MTHFR 677C→T polymorphism is not likely to have a major role in the development of prostate cancer, although it may possibly increase the risk in combination with high plasma folate levels. Further investigation in larger studies is warranted. © 2006 Lippincott Williams & Wilkins, Inc.