Effects of supplemental calcium and vitamin D on the APC/β-catenin pathway in the normal colorectal mucosa of colorectal adenoma patients

Siyu Liu, Elizabeth L. Barry, John A. Baron, Robin E. Rutherford, March E. Seabrook, Roberd M. Bostick

Research output: Research - peer-reviewArticle

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Abstract

APC/β-catenin pathway malfunction is a common and early event in colorectal carcinogenesis. To assess calcium and vitamin D effects on the APC/β-catenin pathway in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, nested within a larger randomized, double-blind, placebo-controlled, partial 2 × 2 factorial chemoprevention clinical trial of supplemental calcium (1200 mg daily) and vitamin D (1000 IU daily), alone and in combination versus placebo, we assessed APC, β-catenin, and E-cadherin expression in colon crypts in normal-appearing rectal mucosa biopsies from 104 participants at baseline and 1-yr follow up using standardized, automated immunohistochemistry and quantitative image analysis. For vitamin D versus no vitamin D, the ratio of APC expression to β-catenin expression in the upper 40% (differentiation zone) of crypts (APC/β-catenin score) increased by 28% (P = 0.02), for calcium versus no calcium it increased by 1% (P = 0.88), and for vitamin D + calcium versus calcium by 35% (P = 0.01). Total E-cadherin expression increased by 7% (P = 0.35) for vitamin D versus no vitamin D, 8% (P = 0.31) for calcium versus no calcium, and 12% (P = 0.21) for vitamin D + calcium versus calcium. These results support (i) that vitamin D, alone or in combination with calcium, may modify APC, β-catenin, and E-cadherin expression in humans in directions hypothesized to reduce risk for colorectal neoplasms; (ii) vitamin D as a potential chemopreventive agent against colorectal neoplasms; and (iii) the potential of APC, β-catenin, and E-cadherin expression as treatable, pre-neoplastic risk biomarkers for colorectal neoplasms.

LanguageEnglish (US)
Pages412-424
Number of pages13
JournalMolecular Carcinogenesis
Volume56
Issue number2
DOIs
StatePublished - Feb 1 2017

Fingerprint

beta Catenin
Vitamin D
Adenoma
Mucous Membrane
Calcium
Cadherins
Colorectal Neoplasms
Placebos
Chemoprevention
Colon
Carcinogenesis
Biomarkers
Immunohistochemistry
Clinical Trials
Biopsy
Direction compound

Keywords

  • biological markers
  • calcium
  • clinical trial
  • colorectal neoplasms
  • vitamin D

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

Effects of supplemental calcium and vitamin D on the APC/β-catenin pathway in the normal colorectal mucosa of colorectal adenoma patients. / Liu, Siyu; Barry, Elizabeth L.; Baron, John A.; Rutherford, Robin E.; Seabrook, March E.; Bostick, Roberd M.

In: Molecular Carcinogenesis, Vol. 56, No. 2, 01.02.2017, p. 412-424.

Research output: Research - peer-reviewArticle

Liu, Siyu ; Barry, Elizabeth L. ; Baron, John A. ; Rutherford, Robin E. ; Seabrook, March E. ; Bostick, Roberd M./ Effects of supplemental calcium and vitamin D on the APC/β-catenin pathway in the normal colorectal mucosa of colorectal adenoma patients. In: Molecular Carcinogenesis. 2017 ; Vol. 56, No. 2. pp. 412-424
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