Development and Validation of Novel Dietary and Lifestyle Inflammation Scores, and Their Associations with Risk for Colorectal Neoplasms Open Access

Byrd, Doratha (Fall 2018)

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Chronically higher inflammation, which may partly result from diet and lifestyle, is implicated in risk for multiple chronic diseases, including colorectal cancer (CRC). The dietary inflammatory index (DII) and empirical DII (EDII), previously developed to characterize dietary contributions to systemic inflammation, have several limitations.

To better reflect dietary/lifestyle contributions to inflammation, we developed novel, dietary (DIS) and lifestyle (LIS) inflammation scores in a subset of the Reasons for Geographic and Racial Differences in Stroke Study. To do this, we selected a priori 19 food groups and four lifestyle characteristics to comprise the DIS and LIS, respectively, and calculated their weights based on their strengths of association with an inflammation biomarker score using multivariable linear regression. The sums of the weighted components constitute the scores. A higher score reflects, on balance, more pro-inflammatory exposures. To validate the scores, we calculated the DIS, LIS, DII, and EDII using cross-sectional data from three study populations with measured circulating inflammation biomarkers. We found that higher DIS and LIS were more strongly, directly associated with inflammation biomarker concentrations in the validation populations than were the DII and EDII, and that the DIS and LIS associations were particularly strong in combination. 

We then investigated associations of the DIS and LIS with incident, sporadic colorectal adenoma in three pooled case-control studies. We found that those in the highest relative to the lowest quintiles of the DIS and LIS had statistically significant higher odds of adenoma. Associations were stronger for high-risk adenomas and for the scores in combination.

We then investigated associations of the DIS and LIS with incident CRC in a large, prospective cohort. We found that higher DIS and LIS were statistically significantly associated with higher risk for incident CRC. Associations were stronger among men, for colon cancers, and for the scores in combination.

Our results support that dietary and lifestyle exposures collectively contribute substantially to systemic inflammation, and support the use of our LIS and of our whole foods-based DIS over the DII and EDII. Our results also suggest that pro-inflammatory diets/lifestyles may be associated with higher risk for colorectal neoplasms.

Table of Contents

Chapter 1. Introduction and Background. 1

Introduction. 1

Inflammation. 2

Mechanisms. 2

Mediators and Effectors of Inflammation. 3

Measuring Systemic Inflammation. 5

Diets, Lifestyles, and Inflammation. 8

Previous Dietary Inflammation Scores 11

Chronic Inflammation and Disease. 13

Colorectal Cancer – an Inflammation Mediated Disease. 14

Epidemiology of Colorectal Cancer 14

Adenomatous Polyps 16

Colorectal Carcinogenesis 17

Colorectal Carcinogenesis and Inflammation. 18

Diets, Lifestyles, and Colorectal Neoplasms 22

Dietary-Associated Inflammation and Colorectal Neoplasms. 24

Gaps in the Literature. 25

Broad, Long-Term Goals of Dissertation. 25

Specific Aims for Dissertation. 26

Chapter 2. Development and Validation of Novel Dietary and Lifestyle Inflammation Scores 29

Abstract 30

Introduction. 31

Methods. 32

Results 40

Discussion. 44

Tables and Figures. 47

Chapter 3. Associations of Novel Dietary and Lifestyle Inflammation Scores with Incident, Sporadic Adenoma 57

Abstract 58

Introduction. 59

Methods. 60

Results 65

Discussion. 67

Table and Figures 72

Chapter 4. Associations of Novel Dietary and Lifestyle Inflammation Scores with Incident Colorectal Cancer in the NIH-AARP Diet and Health Study 79

Abstract 80

Introduction. 81

Methods. 82

Results 88

Discussion. 91

Tables and Figures. 95

Chapter 5. Conclusions 101

Future Directions 103

References 106

Appendix 1. Latent Variable for Systemic Inflammation. 130

Tables and Figures. 133

Appendix 2. Chapter 2 Supplemental Tables 141

Appendix 3. Chapter 3 Supplemental Tables 141

Appendix 4. Chapter 4 Supplemental Tables 141

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