Effects of Supplemental Calcium and Vitamin D on the APC/Beta-Catenin Pathway in the Normal Colorectal Mucosa of Colorectal Adenoma Patients Pubblico

Abstract

Malfunctioning of the APC/beta-catenin pathway is a common and early event in colorectal carcinogenesis. To assess the effects of calcium and vitamin D on the APC/beta-catenin pathway in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, we conducted a randomized, double-blind, placebo-controlled, modified 2x2 factorial chemoprevention clinical trial (n = 104) of supplemental calcium (1,200 mg daily) and vitamin D (1,000 IU daily), alone and in combination versus placebo. APC, beta-catenin, and E-cadherin expression and distributions in colon crypts in normal-appearing rectal mucosa biopsies were detected using standardized automated immunohistochemistry and quantified using image analysis. For vitamin D vs. no vitamin D, the ratio of APC expression to beta-catenin expression in the upper 40% of crypts (APC/beta-catenin score) increased by 28% (P = 0.02), for calcium vs. no calcium it increased by 1% (P = 0.88), and for vitamin D + calcium vs. calcium by 35% (P = 0.01). Total E-cadherin expression increased by 7% (P = 0.35) for vitamin D vs. no vitamin D, 8% (P = 0.31) for calcium vs. no calcium, and 12% (P = 0.21) for vitamin D + calcium vs. calcium. These results support (i) that vitamin D, alone or in combination with calcium, may modify APC, beta-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, beta-catenin, and E-cadherin expression as treatable, pre-neoplastic risk biomarkers for colorectal neoplasms.

Table of Contents

Literature Review. 1

Thesis Manuscript. 14

Figure 1. 32

Table 1. 33

Table 2. 34

Table 3. 37

Summary. 40

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Degree	MSPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Health Sciences, Epidemiology
Parola chiave	clinical trial biomarkers colorectal neoplasms calcium vitamin D
Committee Chair / Thesis Advisor	Bostick, Roberd M, Emory University

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