Journal of the National Cancer Institute Advance Access originally published online on May 27, 2008
JNCI Journal of the National Cancer Institute 2008 100(11):796-804; doi:10.1093/jnci/djn152
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Published by Oxford University Press 2008.
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Serum Vitamin D Concentration and Prostate Cancer Risk: A Nested Case–Control Study
Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (JA, DA, MPP, CCA, NC, WYH, RBH); Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA (UP); Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (UP); Heartland Assays, Ames, IA (RLH, BWH); Division of Preventive Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL (JMS)
Correspondence to: Jiyoung Ahn, PhD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Blvd, Bethesda, MD 20892 (e-mail: Ahnj{at}mail.nih.gov).
Background: Epidemiological studies have yielded inconsistent associations between vitamin D status and prostate cancer risk, and few studies have evaluated whether the associations vary by disease aggressiveness. We investigated the association between vitamin D status, as determined by serum 25-hydroxyvitamin D [25(OH)D] level, and risk of prostate cancer in a case–control study nested within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
Methods: The study included 749 case patients with incident prostate cancer who were diagnosed 1–8 years after blood draw and 781 control subjects who were frequency matched by age at cohort entry, time since initial screening, and calendar year of cohort entry. All study participants were selected from the trial screening arm (which includes annual standardized prostate cancer screening). Conditional logistic regression was used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) by quintile of season-standardized serum 25(OH)D concentration. Statistical tests were two-sided.
Results: No statistically significant trend in overall prostate cancer risk was observed with increasing season-standardized serum 25(OH)D level. However, serum 25(OH)D concentrations greater than the lowest quintile (Q1) were associated with increased risk of aggressive (Gleason sum 
7 or clinical stage III or IV) disease (in a model adjusting for matching factors, study center, and history of diabetes, ORs for Q2 vs Q1 = 1.20, 95% CI = 0.80 to 1.81, for Q3 vs Q1 =1.96, 95% CI = 1.34 to 2.87, for Q4 vs Q1 = 1.61, 95% CI = 1.09 to 2.38, and for Q5 vs Q1 = 1.37, 95% CI = 0.92 to 2.05; Ptrend = .05). The rates of aggressive prostate cancer for increasing quintiles of serum 25(OH)D were 406, 479, 780, 633, and 544 per 100 000 person-years. In exploratory analyses, these associations with aggressive disease were consistent across subgroups defined by age, family history of prostate cancer, diabetes, body mass index, vigorous physical activity, calcium intake, study center, season of blood collection, and assay batch.
Conclusion: The findings of this large prospective study do not support the hypothesis that vitamin D is associated with decreased risk of prostate cancer; indeed, higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease.
| CONTEXT AND CAVEATS Prior knowledge Although data from laboratory studies have suggested that vitamin D inhibits prostate cell proliferation and differentiation, epidemiological studies have yielded mixed results on the association between vitamin D status and prostate cancer risk. Study design Nested case–control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. All of the men in this analysis were receiving regular prostate cancer screening. Contributions An increase in season-standardized serum 25-hydroxyvitamin D level was not associated with a decreased risk of prostate cancer. There was some evidence that men with vitamin D levels above the lowest quintile had an increased risk of prostate cancer with aggressive characteristics, but no clear monotonic trend was evident. Implications Higher levels of serum 25-hydroxyvitamin D may not reduce the risk of prostate cancer; indeed, it is possible that higher levels are associated with increased risk of aggressive disease. Limitations Only a single baseline vitamin D measurement was available. Whether vitamin D levels could affect prostate-specific antigen levels in some cancers, causing a diagnosis bias, is not known. As with all epidemiology studies, unmeasured confounders could account for the results.
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Manuscript received November 26, 2007; revised March 25, 2008; accepted April 16, 2008.
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  L. A. Mucci and D. Spiegelman Vitamin D and Prostate Cancer Risk--A Less Sunny Outlook? J Natl Cancer Inst, June 4, 2008; 100(11): 759 - 761. [Full Text] [PDF]
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