Associations of base excision repair genotypes with incident, sporadic colorectal adenoma according to antioxidant enzyme genotypes and oxidative balance-related environmental exposures Open Access

Abstract

Associations of individual base excision repair (BER) genotypes with colorectal adenoma risk are unclear, but likely modest. However, genetic risk scores (GRS) that aggregate information from multiple genetic variants might be useful for assessing genetic predisposition to colorectal adenoma. We conducted an analysis of 1,073 Caucasians aged from 30-74 years using data pooled from the three colonoscopy-based case-control studies of incident, sporadic colorectal adenoma that collected blood for genotyping and extensive dietary and other data. Associations of individual single nucleotide polymorphisms (SNPs) were assessed and used to combine information from multiple risk variants into a BER GRS based on 74 SNPs in 14 BER genes and an antioxidant enzymes GRS based on 22 SNPs in 3 antioxidant enzyme genes using two methods: a simple variant allele count method (count GRS) and a weighted method (weighted GRS). We also considered 15 extrinsic factors with known pro- or anti-oxidant properties to construct an oxidative balance score (OBS). Multivariable unconditional logistic regression was used to assess associations of BER genotypes with incident, sporadic colorectal adenoma, overall and according to the antioxidant enzyme GRS and the OBS. The odds ratio (OR) for those in the highest relative to the lowest tertile of the weighted BER GRS was 2.65 (95% confidence interval [CI], 1.58-4.43; Ptrend <0.001). However, there were no clear patterns to suggest possible BER GRS-antioxidant enzymes GRS or -OBS interactions. Our findings suggest that BER genotypes collectively may be associated with risk for incident sporadic colorectal adenomas.

Table of Contents

Chapter I: Background 1

Chapter II: Manuscript 10

Abstract 10

Introduction 12

Methods 13

Results 19

Discussion 21

References 27

Tables 38

Chapter III: Summary 43

Appendix 1. List of the Base excision repair genes investigated 45

Appendix 2. Individule base excision repair genes SNPs analysis 47

Appendix 3. Individule antioxidant enzyme genes SNPs analysis 53

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
Keyword	Base excision repair Oxidative balance Colorectal adenoma
Committee Chair / Thesis Advisor	Bostick, Roberd M, Emory University

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