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Mol Carcinog. 2017 Feb;56(2):412-424. doi: 10.1002/mc.22504. Epub 2016 Jun 14.

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

Author information

1
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.
2
Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
3
Department of Medicine, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
4
University of North Carolina School of Medicine, Chapel Hill, North Carolina.
5
Division of Digestive Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia.
6
Consultants in Gastroenterology, West Columbia, South Carolina.
7
Winship Cancer Institute, Emory University, Atlanta, Georgia.

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.

KEYWORDS:

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

PMID:
27254743
PMCID:
PMC5586148
DOI:
10.1002/mc.22504
[Indexed for MEDLINE]
Free PMC Article

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