Calcium and Milk Product Intakes and Risk of Colorectal Neoplasia and Other Health Outcomes Open Access

Abstract

There is extensive evidence that calcium and calcium-rich foods, such as milk products, are associated with lower risk of colorectal neoplasms, and supplemental calcium reduced sporadic colorectal adenoma recurrence in two of three large randomized controlled trials. However, clinical trials suggest that milk product consumption may increase circulating insulin-like growth factor 1 (IGF-1) levels, and cross-sectional studies reported positive associations of milk consumption with IGF-1 concentrations. IGF-1 concentrations were also positively associated with risk of colorectal cancer. However, there is no evidence on the effect of supplemental calcium on IGF-1, and there is inconsistent evidence on the associations of calcium and milk product intakes with risk for all-cause and cause-specific mortality. The purpose of this dissertation was to further clarify the role of calcium and milk products in colorectal neoplasia and other health outcomes. The specific research aims were to: 1) investigate associations of calcium and milk products with risk for colorectal adenomatous polyps; 2) investigate associations of the non-calcium component of milk products with risk for adenomas and mortality; and 3) investigate the association of calcium and milk products with risk for all-cause and cause-specific mortality. These aims were addressed by analyzing data from three colonoscopy-based case-control studies of incident, sporadic colorectal adenoma, a clinical trial of calcium supplementation in adenoma patients, and a national population-based prospective cohort study. We found an inverse association of dietary calcium with risk of adenomas, consistent with previous literature. We found no appreciable effects of 1.0 or 2.0g of daily supplemental calcium relative to placebo on levels of IGF-1, IGFBP-3, or the IGF-1:IGFBP-3 molar ratio. IGF-1 and IGFBP-3 concentrations were inversely associated with age and were lower in women, which is consistent with most previous literature. Our estimation of milk product residuals is a novel modification of the energy adjustment method that can be utilized to estimate the non-calcium/non-fat component of milk, and our analyses suggest that milk fat may be directly associated with all-cause mortality, the non-calcium/non-fat, IGF-1-containing component of milk may be directly associated with cancer mortality, and calcium intake independent of milk product intake may not be associated with mortality.

Table of Contents

CHAPTER 1. INTRODUCTION AND BACKGROUND ........................................................................... 1

INTRODUCTION .......................................................................................................................... 1

BACKGROUND ............................................................................................................................. 2

Colorectal Cancer ....................................................................................................................... 2

Calcium .................................................................................................................................... 4

Milk Products.............................................................................................................................. 6

Calcium, Milk Products, and Mortality ............................................................................................ 10

Gaps in the Literature Addressed by this Dissertation ....................................................................... 13

DISSERTATION RESEARCH PLAN ................................................................................................... 14

Objectives, Specific Aims, and Study Hypotheses ............................................................................ 14

Methods for Aim 1 ..................................................................................................................... 15

Methods for Aim 2 ..................................................................................................................... 17

Methods for Aim 3 ..................................................................................................................... 20

Significance and Impact of the Study ............................................................................................ 21

CHAPTER 2. Associations of Calcium and Milk Product Intakes with Incident, Sporadic

Colorectal Adenomas ............................................................................................................... 22

ABSTRACT ................................................................................................................................ 23

INTRODUCTION .......................................................................................................................... 24

MATERIALS AND METHODS ........................................................................................................... 25

RESULTS ................................................................................................................................... 28

DISCUSSION .............................................................................................................................. 30

TABLES...................................................................................................................................... 37

CHAPTER 3. Circulating insulin-like growth factor-1 and insulin-like growth factor binding protein-3:

Correlates and responses to calcium supplementation in colorectal adenoma patients.....................42

ABSTRACT ................................................................................................................................. 43

INTRODUCTION ........................................................................................................................... 44

MATERIALS AND METHODS ............................................................................................................ 45

RESULTS .................................................................................................................................... 49

DISCUSSION ............................................................................................................................... 50

TABLES....................................................................................................................................... 54

CHAPTER 4. Associations of calcium and dairy products with all-cause and cause-specific

mortality: REasons for Geographic and Racial Differences in Stroke (REGARDS) Prospective

Cohort Study ............................................................................................................................. 58

ABSTRACT .................................................................................................................................. 59

INTRODUCTION ............................................................................................................................ 60

MATERIALS AND METHODS ............................................................................................................. 61

RESULTS ..................................................................................................................................... 65

DISCUSSION ................................................................................................................................ 67

TABLES........................................................................................................................................ 72

CHAPTER 5. DISCUSSION AND FUTURE DIRECTIONS ........................................................................ 81

Summary and Public Health Implications ............................................................................................ 81

Future Directions .......................................................................................................................... 83

REFERENCES ................................................................................................................................ 86

APPENDIX .................................................................................................................................... 106

About this Dissertation

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Health Sciences, Nutrition Health Sciences, Epidemiology
Keyword	Dairy Calcium insulin-like growth factor Milk IGF-1 Colorectal cancer
Committee Chair / Thesis Advisor	Bostick, Roberd M, Emory University
Committee Members	Judd, Suzanne, University of Alabama Fedirko, Veronika , Emory University Vos, Miriam Benedicta, Emory University Flanders, W Dana, Emory University

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