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

Roswell Park Cancer Institute50 enrolled

Overview

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.

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).

Study Type

INTERVENTIONAL

Allocation

Purpose

SUPPORTIVE_CARE

Masking

NONE

Enrollment

Conditions

Colorectal Cancer

Interventions

cholecalciferolDIETARY_SUPPLEMENT

Oral

polymerase chain reactionGENETIC

companion study

polymorphism analysisGENETIC

companion study

protein expression analysis

Eligibility

Sex: ALLMin age: 18 YearsMax age: 120 Years

Medical Language ↔ Plain English

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

Locations (1)

Roswell Park Cancer Institute

Buffalo, New York, United States

Outcomes

Primary Outcomes

Identification of CYP24 single nucleotide polymorphisms (SNPs)

Time frame: 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)

Time frame: At baseline

Effect of CYP24 SNPs on serum vitamin D3 metabolites and PTH levels during cholecalciferol treatment

Time frame: Baseline, days 14, 30, 60, 90, 180, 270, 360

CYP24 splicing, protein expression, and enzyme activity at baseline and during cholecalciferol treatment

Time frame: Baseline, days 14, 30, 60, 90, 180, 270, 360

Relationship between serum cholecalciferol pharmacokinetic parameters and CYP24 SNPs, splicing variants, and enzyme activity

Time frame: Baseline, days 14, 30, 60, 90, 180, 270, 360

Data from ClinicalTrials.gov

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