ORIGINAL PAPER Serum folate and prostate-specific antigen in the United States Yueh-Ying Han • Ji Young Song • Evelyn O. Talbott Received: 25 February 2013 / Accepted: 15 May 2013 / Published online: 24 May 2013 Ó Springer Science+Business Media Dordrecht 2013 Abstract Purpose Increased evidence suggests that folate may play a significant role in cancer development. This study investigates the association between levels of serum folate and prostate-specific antigen (PSA), a biomarker for pros- tate cancer detection. Methods Using data from the 2007 to 2010 National Health and Nutrition Examination Survey, a total of 3,293 men aged 40 years and older with serum PSA and folate measures were studied. Total PSA level (tPSA) and percent free/total PSA ratio (%fPSA) were major outcomes. The alternative cutpoints were used to categorize these mea- sures as higher risks of prostate cancer (tPSA: C10, C4, and C2.5 ng/ml; %fPSA: B15 and B5 %). Serum folate level was analyzed as continuous and as quintiles. Asso- ciation between serum folate and PSA levels were evalu- ated by multivariate linear and logistic regressions. Results Higher serum folate levels were associated with decreased log10-transformed tPSA (b =-001, p = 0.061) and increased %fPSA (b = 0.064, p = 0.012). Adjusting for age, race/ethnicity, socioeconomic status, use of non- steroidal anti-inflammatory drugs, body mass index, and smoking status, higher serum folate (fifth quintile) was associated with lower odds of having higher tPSA (C10 ng/ml) and lower %fPSA (B25 %): (tPSA: odds ratio, OR associated with fifth to first quintile of folate level = 0.42; 95 % confidence interval, CI = 0.21, 0.83; p for trend = 0.022 and %fPSA: OR = 0.71; 95 % CI = 0.52, 0.95; p for trend = 0.044). Conclusions Results of this study suggest that higher folate status may be protective against elevated PSA levels among men without diagnosed prostate cancer. Additional epidemiologic studies are necessary to confirm our findings and to investigate potential mechanisms. Keywords Folate Á Prostate-specific antigen Á Prostate cancer Á NHANES Introduction Folate is a cofactor in the transfer of one-carbon moieties and is one of the primary methyl donors that plays key role in DNA synthesis, repair, and methylation [1]. Folate deficiency has been related to the development of anemia, cardiovascular diseases, and neural tube defects. Increased evidences suggest that folate may play a dual role, which prevents early lesions but promotes growth of existing cancers, in carcinogenesis [2]. Alterations in DNA meth- ylation, disruption of DNA integrity, and disruption of DNA repair were observed with folate depletion and that could enhance carcinogenesis by altering the expression of tumor suppressor genes and proto-oncogenes [3]. Mean- while, folate supplementation increases the supply of nucleotides that are required for replication of mutated cells and may stimulate formation of neoplastic foci in the target organs [4]. Electronic supplementary material The online version of this article (doi:10.1007/s10552-013-0236-7) contains supplementary material, which is available to authorized users. Y.-Y. Han (&) Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA e-mail: hany2@upmc.edu J. Y. Song Á E. O. Talbott Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, A526 Crabtree Hall, Pittsburgh, PA 15261, USA e-mail: eot1@pitt.edu 123 Cancer Causes Control (2013) 24:1595–1604 DOI 10.1007/s10552-013-0236-7