DNA Changes That Affect Vitamin D Metabolism in Patients With Colorectal Cancer Receiving Vitamin D Supplements

Study Overview
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Brief Summary
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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
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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).

Official Title
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Identification of 24-Hydroxylase Polymorphisms and Splicing Variants That Modulate Vitamin D Oxidative Metabolism and Serum Pharmacokinetics in Patients With Colorectal Cancer on Cholecalciferol Therapy

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Dietary Supplement: cholecalciferol
* Genetic: polymerase chain reaction
* Genetic: polymorphism analysis
* Genetic: protein expression analysis
* Genetic: reverse transcriptase-polymerase chain reaction
* Genetic: western blotting
* Other: high performance liquid chromatography
* Other: laboratory biomarker analysis
* Other: pharmacological study
* Procedure: adjuvant therapy
* Procedure: immunoscintigraphy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Prior or current documented diagnosis of colorectal cancer All stages 25OH-D3 level < 50 ng/mL PATIENT CHARACTERISTICS: 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 mg/dL) 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 Units (IU) Nondietary vitamin D supplements should not have exceeded 800 IU/day within the past 2 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral Cholecalciferol<br>Patients receive oral cholecalciferol 2000 IU once daily for 1 year | Dietary Supplement: cholecalciferol<br>* Oral<br>Genetic: polymerase chain reaction<br>* companion study<br>Genetic: polymorphism analysis<br>* companion study<br>Genetic: protein expression analysis<br>* companion study<br>Genetic: reverse transcriptase-polymerase chain reaction<br>* companion study<br>Genetic: western blotting<br>* companion study<br>Other: high performance liquid chromatography<br>* companion study<br>Other: laboratory biomarker analysis<br>* companion study<br>Other: pharmacological study<br>* companion study<br>Procedure: adjuvant therapy<br>* Additional therapy<br>Procedure: immunoscintigraphy<br>* additional testing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of CYP24 single nucleotide polymorphisms (SNPs) |  | Baseline, days 14, 30, 60, 90, 180, 270, 360 | 
| Effect of CYP24 SNPs on baseline serum vitamin D3 metabolites (25-D3, 24,25-D3, and 1,25-D3), and parathyroid hormone levels (PTH) |  | At baseline | 
| Effect of CYP24 SNPs on serum vitamin D3 metabolites and PTH levels during cholecalciferol treatment |  | Baseline, days 14, 30, 60, 90, 180, 270, 360 | 
| CYP24 splicing, protein expression, and enzyme activity at baseline and during cholecalciferol treatment |  | Baseline, days 14, 30, 60, 90, 180, 270, 360 | 
| Relationship between serum cholecalciferol pharmacokinetic parameters and CYP24 SNPs, splicing variants, and enzyme activity |  | Baseline, days 14, 30, 60, 90, 180, 270, 360 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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