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

Liu, Siyu (2015)

Permanent URL: https://etd.library.emory.edu/concern/etds/3b591921b?locale=en
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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

Table of Contents

Literature Review ..................... 1

Thesis Manuscript ..................... 14

Figure 1 .................................. 32

Table 1 ................................... 33

Table 2 ................................... 34

Table 3 ................................... 37

Summary ................................ 40

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