Letter to the Editor Circulating Vitamin D and Risk of Prostate Cancer—Letter Gary G. Schwartz In a large case–control study nested within a cohort in Finland, Albanes and colleagues reported an association between higher serum levels of 25-hydroxyvitamin D (25- OHD) and an increased risk of prostate cancer (1). As the authors acknowledge, this finding is contrary to an exten- sive literature that shows that vitamin D metabolites exert prodifferentiating, antiproliferative, and antimetastatic effects on prostate cancer cells. The purpose of this letter is to note that the association between 25-OHD and prostate cancer observed by Albanes and colleagues is dependent upon calcium intake. Calcium intake is an established risk factor for prostate cancer (2). The authors present the association between quintiles of serum 25-OHD and risk of prostate cancer stratified by "high" and "low" calcium intake in Table 4 (p. 1855). For the stratum of "high" calcium intake (calcium 1,338 mg/d), the ORs for quintiles 2 to 5 are 1.40, 1.65, 1.60, and 1.82 and are statistically significant for quintiles 3 to 5. For the stratum of "low" calcium intake (calcium < 1,338 mg/d), the corresponding ORs are 1.09, 0.99, 0.93, and 1.15. None of the ORs for the stratum of "low" calcium intake appears elevated and none are statistically significant. Because the association between serum 25-OHD and risk of prostate cancer was observed only among men with a calcium intake 1,338 mg/d [an intake that sub- stantially exceeds the recommended calcium intake for 51- to 70-year-old men in Finland (800 mg/d) and the United States (1,000 mg/d); refs. 3, 4], the authors’ con- clusion that "men with higher vitamin D blood levels are at increased risk of developing prostate cancer" is mis- leading. Rather, the data suggest either that there is an interaction between calcium intake and 25-OHD levels and/or that the association is due to residual confounding by calcium intake (5). Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed. Received September 27, 2011; accepted October 17, 2011; published OnlineFirst July 22, 2011. References 1. Albanes D, Mondul AM, Yu K, Pareisi D, Horst RL, Virtamo J, et al. Serum 25-hydroxy vitamin D and prostate cancer risk in a large nested case- control study. Cancer Epidemiol Biomarkers Prev 2011;20:1850–60. 2. Rowland GW, Schwartz GG, John EM, Ingles SA. Calcium intake and prostate cancer among African Americans: effect modification by Vita- min D receptor calcium absorption genotype. J Bone Min Res. 2011 Sep 1. [Epub ahead of print]. 3. Hirvonen T, Tapanainin H, Valsta L, Hannja M-L, Aro A, Pietenen P. Efficacy and safety of food fortification with calcium among adults in Finland. Pub Health Nutr 2006;9:792–97. 4. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PH, Clinton SK, et al. The 2011 report on Dietary Reference Intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 2011;96:53–8. 5. Schwartz GG. Sunlight, vitamin D and prostate cancer epidemiology. In: Feldman D, Pike JW, Adams JS, editors. Vitamin D. 3rd ed. Amsterdam, the Netherlands: Elsevier; 2011. p. 965–78. Author's Affiliation: Departments of Cancer Biology and Epidemiology and Prevention, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina Corresponding Author: Gary G. Schwartz, Departments of Cancer Bio- logy and Epidemiology and Prevention, Wake Forest Baptist Medical Center, Medical Center Blvd, Winston-Salem, NC 27157. Phone: 336- 716-7446; Fax: 336-716-5687; E-mail: gschwart@wakehealth.edu doi: 10.1158/1055-9965.EPI-11-0910 Ó2011 American Association for Cancer Research. Cancer Epidemiology, Biomarkers & Prevention Cancer Epidemiol Biomarkers Prev; 21(1) January 2012 246 on June 9, 2020. © 2012 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from Published OnlineFirst November 1, 2011; DOI: 10.1158/1055-9965.EPI-11-0910