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Calcium, Vitamin D, and Colon Cancer Risk Biomarkers

Phase 2
30 Years
74 Years
Open (Enrolling)
Colorectal Adenomatous Polyps

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Trial Information

Calcium, Vitamin D, and Colon Cancer Risk Biomarkers

There is strong biologic plausibility and animal experimental evidence for protection
against colorectal cancer by calcium and vitamin D, calcium significantly reduced adenoma
recurrence in a large clinical trial in humans (yet the previously reported observational
evidence, although generally supportive, is inconsistent), and the observational literature
strongly supports protection from vitamin D. A close physiological relationship between
calcium and vitamin D has long been known. Yet, other than a possible reduction of
colorectal epithelial cell proliferation by calcium, the effects of calcium and vitamin D,
individually or jointly, on the normal human colorectal epithelium remain unknown. There
have been no clinical trials involving vitamin D individually or jointly with calcium
related to colorectal cancer chemoprevention in humans. There are currently no generally
accepted pre-neoplastic biomarkers of risk for colorectal cancer other than the possible
exception of proliferation markers that, at best, have limited usefulness as individual
markers. Based on recent advances in understanding the molecular basis of colorectal
cancer, we developed a panel of newer, plausible, reliable, immunohistochemically detected
biomarkers that provides molecular phenotyping of the normal appearing colorectal
epithelium: 1) inflammation (COX-2), 2) the expression of genes involved in the normal
structure and function of the colorectal epithelium that have been found to be altered early
in the two major colorectal carcinogenesis pathways (APC, MSH2, MLH1), and 3) a more
complete picture of the cell cycle events in colorectal epithelial crypt cells (short and
long-term proliferation: MIB-1 and telomerase; differentiation: p21; apoptosis inhibition
and promotion: bcl-2, bax, and bak) that has not yet been tested in a chemoprevention

To address these needs, we will conduct a preliminary, randomized, double-blind,
placebo-controlled, 2 x 2 factorial chemoprevention trial (n = 88) of calcium 2,000 mg/day
and vitamin D3 800 IU/day, alone and in combination vs placebo over 6 months in patients
with recent removal of sporadic adenomatous colorectal polyps, to investigate their effects
on the individual components and aggregate profile of our colorectal cancer risk biomarker
panel. We will also examine study results stratified by NSAID use and Bsm I vitamin D
receptor genotypes. The preliminary estimates of treatment effect sizes and variabilities
will be used to refine the biomarker panel and study design and to calculate the needed
sample size for a potential full-scale study.

We assert that using biological measurements of risk, as they have for ischemic heart
disease, will result in a decline in colorectal cancer incidence and mortality. The
proposed project is borne of this vision, and has intertwined missions of exploring the
efficacy of two plausible and evidentially well-supported dietary agents, calcium and
vitamin D, on the modulation of a plausible panel of molecular phenotypic biomarkers of risk
for colorectal neoplasia.

Inclusion Criteria:

- age 30-74

- adenomatous colon polyp within past 3 years

- general good health with life expectancy of at least 2 years

- available for 8 months and able to come for clinic visits

Exclusion Criteria:

- cancer within 5 years

- active major disease

- renal impairment

- history of kidney stones

- significant dietary change or weight loss within past 6 months

- unable to forego usual calcium or vitamin D use during study

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Outcome Measure:

Biomarkers of Risk for Colorectal Neoplasms

Outcome Description:

A panel of putative biomarkers of risk for colorectal neoplasms in biopsies of normal appearing rectal mucosa: COX-2, APC, MSH-2, MLH1, MIB-1, telomerase, p21, bcl-2, bax, bak, β-catenin, E-cadherin, TGFα, TGFβ1, calcium sensing receptor, vitamin D receptor, CYP27B1, CYP24, 8-OH-dG

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Roberd M Bostick, MD, MPH

Investigator Role:

Principal Investigator

Investigator Affiliation:

Emory University, Rollins School of Public Health & Winship Cancer Institute


United States: Federal Government

Study ID:




Start Date:

May 2005

Completion Date:

February 2013

Related Keywords:

  • Colorectal Adenomatous Polyps
  • colonic polyps
  • adenomatous polyps
  • colon cancer prevention
  • dietary supplements
  • Colonic Neoplasms
  • Polyps
  • Adenomatous Polyps



The Emory Clinic, Division of Digestive Diseases Atlanta, Georgia  30322