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Vitamin D and Risks of Prostate and Colorectal Cancers: Study Update and Expansion

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Principal Investigator

Name
Regina Ziegler

Degrees
-

Institution
-

Position Title
-

Email
regina.ziegler@nih.gov

About this CDAS Project

Study
PLCO (Learn more about this study)

Project ID
2008-0224

Title
Vitamin D and Risks of Prostate and Colorectal Cancers: Study Update and Expansion

Summary
Experimental data suggest that vitamin D may protect against prostate and colorectal cancer. In humans, geographic and ethnic comparisons also raise the possibility that vitamin D may protect against these diseases. Serum-based evaluations of the pro-hormonal, 25-hydroxy vitamin D [25(OH)D] with colorectal cancer risk have generally supported this; in a recent meta-analysis of these studies, individuals with serum 25(OH)D levels equal to or greater than 33 ng/mL (82 nmol/L) had a 50% lower incidence of colorectal cancer than those with relatively low levels (< 12 ng/mL or 30 nmol/L)(1). In contrast, the relationship of 25(OH)D with prostate cancer has been inconsistent or null (2). Recent studies, however, suggest prostate cancer risk reductions in relation to higher serum levels of 1,25-dihydroxy vitamin D [1,25(OH)2D], the homeostatically regulated and biologically active form of vitamin D (3), indicating that further in-depth evaluations are needed. Because serum concentrations do not entirely reflect prostate organ-specific vitamin D status, our understanding may be incomplete; published studies suggest that prostate and colorectal tumor tissue has altered expression of the vitamin D receptor (VDR) (4), of enzymes responsible for the synthesis (CYP27A1 and CYP27B1) (5;6) and catabolism (CYP24A1) (7) of 1,25(OH)2D, and of parathyroid hormone (PTH) (8), a regulator of 1,25(OH)2D concentration. Using tissue microarrays from the prostate and colorectal cancer cases, we now propose to determine the extent in prostate and colon cancers of vitamin D-related CpG island promoter methylation (CYP27B1 and CYP24A1) and tumor protein expression (CYP27A1, CYP27B1, CYP24A1, PTH, and VDR) and determine if these phenotypic patterns are related to underlying genetics or are differential with respect to cancer subtypes. We will examine the relationship of serum vitamin D to prostate and colorectal cancer risks, and will also examine serum-tissue correlation.

Aims

1. Determine the association between serum 25(OH)D (already assayed) and 1,25(OH)2D concentrations and risk of aggressive prostate cancer. 2. Determine the relationship of CYP27A1, CYP27B1, CYP24A1, PTH, and VDR protein levels in prostate cancer tissue,to prostate cancer aggressiveness, in a case-case analysis. 3. Determine the relationship of CYP27B1 and CYP24A1 promoter methylation to CYP27B1 and CYP24A1 protein expression in prostate cancer tissue and characterize differential methylation-expression patterns in aggressive and non-aggressive prostate cancer cases. 4. Determine the association between serum 25(OH)D concentrations and risk of colorectal cancer. 5. Determine CYP27A1, CYP27B1, CYP24A1, PTH, and VDR protein levels in colorectal cancer tissue compared with adjacent normal tissue, and examine the relationship stratified by colorectal cancer subtypes (i.e. APC, p53, and KRAS positive [assay approved under Huang 2007-00220]). 6. Determine the relationship of CYP27B1 and CYP24A1 promoter methylation to CYP27B1 and CYP24A1 protein expression in colorectal cancer subtypes.

Collaborators

Christian Abnet (NCI, DCEG)
Jiyoung Ahn (NCI, DCEG)
Nilanjan Chatterjee (NCI, DCEG)
Demetrius Albanes (NCI, DCEG)
Richard Hayes (NCI, DCEG)
Wen-Yi Huang (NCI, DCEG)
Arthur Schatzkin (NCI, DCEG)

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