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
PURPOSE: This clinical trial is studying changes in DNA that affect vitamin D metabolism in
patients with colorectal cancer receiving vitamin D supplements.
- To identify CYP24 single nucleotide polymorphisms (SNPs) using peripheral blood
mononuclear cell genomic DNA from patients with colorectal cancer receiving
- 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).
- Prior or current documented diagnosis of colorectal cancer
- All stages
- 25OH-D3 level < 50 ng/mL
- ECOG performance status 0-2
- Life expectancy > 6 months
- Serum creatinine < 2.0 mg/dL
- Serum bilirubin < 2.0 mg/dL
- No prior or current hypercalcemia (defined as albumin corrected serum calcium < 10.2
- No known contraindication for vitamin D supplementation
- No genitourinary stones within the past 5 years
- No severe comorbid conditions such as uncompensated heart failure or active infection
PRIOR CONCURRENT THERAPY:
- No supplemental vitamin D beyond what is provided through the study
- At least 2 months since prior vitamin D supplementation exceeding 800 International
- Nondietary vitamin D supplements should not have exceeded 800 IU/day within the
past 2 months