EFFECTS OF CALCIUM AND/OR VITAMIND SUPPLEMENTATION ON GOBLET CELL MUCIN CONTENT IN NORMAL COLON MUCOSA OF SPORADIC COLORECTAL ADENOMA PATIENTS Open Access

Tseng, Petty (2013)

Permanent URL: https://etd.library.emory.edu/concern/etds/xd07gs93w?locale=en
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Abstract

Background: Calcium and vitamin D favorably modify molecular phenotypic profiles of colon crypts in the normal colorectal mucosa of colorectal adenoma patients, but their effects on goblet cell mucin content are unknown. Methods: We conducted a pilot, randomized, double-blind, placebo-controlled 2×2 factorial chemoprevention clinical trial of supplemental calcium 2,000 mg and/or vitamin D3 800 IU daily versus placebo over six months in patients (n = 92) with a history of at least one pathology-confirmed colorectal adenoma. Biopsies of normal-appearing rectal mucosa obtained at baseline and at six-months follow-up were histologically sectioned, and goblet cell mucin area and distributions within full-length crypts were quantified by image analysis. The results were analyzed using mixed linear models. Results: Relative to the placebo group, the mean goblet cell area increased by 16% (p = 0.21), 6% (P = 0.53), and 3% (P = 0.96) in the vitamin D, calcium, and calcium plus vitamin D groups, respectively. There was little indication that any possible changes in goblet cell mucin area differed along the lengths of crypts except, possibly, in the lower 20% of crypts in the vitamin D group where there was an estimated 24% increase (p = 0.07). Conclusion: Calcium and/or vitamin D3 supplementation do not appear to appreciably change goblet cell mucin content in the normal colorectal mucosa of sporadic adenoma patients. Impact: These results, taken together with previous findings, support the use of colon crypt molecular phenotypic markers over histological characteristics as modifiable pre-neoplastic biomarkers of risk for colorectal neoplasms in humans.

Table of Contents

CHAPTER I 1
BACKGROUND 1
Descriptive Epidemiology 1
Colorectal Carcinogenesis 2
Environmental Factors in Colorectal Cancers 4
Human Studies of Calcium and Colorectal Cancer Risk 5
Studies of Vitamin D and Colorectal Cancer Risk 7
Studies of Calcium plus Vitamin D and Colorectal Cancer Risk 8
Surrogate End-Point Biomarkers (SEBs) in Colorectal Cancer 8
Crypt Histology, Goblet Cells, and Colorectal Cancer 10
Review of Studies in Calcium, Vitamin D, and Colon Crypt Goblet Cells or Mucin 11
CHAPTER II 12
MANUSCRIPT FOR SUBMISSION FOR PUBLICATION IN A PEER-REVIEWED JOURNAL TO REPORT THE THESIS FINDINGS 12
Abstract 14
Introduction 15
Patients and Methods 16
Participant Population 16
Clinical Trial Protocol 16
Tissue Collection and Processing 17
Image Analysis of the Normal Colon Crypts 18
Statistical Analysis 19
Results 20
Characteristics of Study Participants 20
Graphical Assessment of Goblet Cell Mucin Areas in Normal Colorectal Crypts 20
Effects of Calcium and/or Vitamin D Supplementation on Goblet Cell Mucin Area in Normal Colorectal Crypts 21
Discussion 21
TABLES and FIGURES 24
Chapter III 29
STUDY IMPLICATIONS AND FUTURE RESEARCH DIRECTIONS 29
References 30
APPENDIX 35
SUPPLEMENTAL TABLES AND FIGURES 35

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