DNA Changes That Affect Vitamin D Metabolism in Patients With Colorectal Cancer Receiving Vitamin D Supplements
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Study type: Interventional

Summary: 
      RATIONALE: Studying samples of blood from patients with cancer in the laboratory may help
      doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.

      PURPOSE: This clinical trial is studying changes in DNA that affect vitamin D metabolism in
      patients with colorectal cancer receiving vitamin D supplements.
    

Detailed description: 
      OBJECTIVES:

        -  To identify CYP24 single nucleotide polymorphisms (SNPs) using peripheral blood
           mononuclear cell genomic DNA from patients with colorectal cancer receiving
           cholecalciferol supplementation.

        -  To evaluate the effects of these CYP24 SNPs on baseline serum vitamin D_3 metabolites
           (25-D_3, 24,25-D_3, and 1,25-D_3), and parathyroid hormone levels (PTH).

        -  To evaluate the effects of these CYP24 SNPs on serum vitamin D_3 metabolites and PTH
           levels during cholecalciferol treatment.

        -  To examine CYP24 splicing, protein expression, and enzyme activity at baseline and
           during cholecalciferol treatment.

        -  To determine the relationship, if any, between serum cholecalciferol pharmacokinetic
           parameters and CYP24 SNPs, splicing variants, and enzyme activity.

      OUTLINE: Patients receive oral cholecalciferol 2000 IU once daily for 1 year. Patients
      without response to vitamin D supplementation (serum 25-D_3 level < 32 ng/mL) by 6 months
      will have their cholecalciferol dose increased to 4000 IU once daily.

      Blood is collected at baseline and on days 14, 30, 60, 90, 180, 270, and 360. Peripheral
      blood mononuclear cells for CYP24 genotyping, protein expression, enzyme activity, and
      splicing variants are analyzed by polymerase chain reaction (PCR), western blot, high
      performance liquid chromatography, and reverse transcriptase PCR, respectively. Serum is
      analyzed for vitamin D_3 metabolite levels (by radioimmunoassay), calcium (to monitor for
      hypercalcemia), and parathyroid hormone assays (to measure vitamin D effect).
    

Intervention name(s): cholecalciferol; polymerase chain reaction; polymorphism analysis; protein expression analysis; reverse transcriptase-polymerase chain reaction; western blotting; high performance liquid chromatography; laboratory biomarker analysis; pharmacological study; adjuvant therapy; immunoscintigraphy
Intervention type(s): Dietary Supplement; Genetic; Genetic; Genetic; Genetic; Genetic; Other; Other; Other; Procedure; Procedure
Intervention description(s): Oral; companion study; companion study; companion study; companion study; companion study; companion study; companion study; companion study; Additional therapy; additional testing
Intervention MeSH terms: Cholecalciferol; Vitamin D
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: recurrent colon cancer; stage I colon cancer; stage II colon cancer; stage III colon cancer; stage IV colon cancer; recurrent rectal cancer; stage I rectal cancer; stage II rectal cancer; stage III rectal cancer; stage IV rectal cancer