Association of Colorectal Cancer Susceptibility Loci Alone and in Combination with Adherence to the WCRF/AICF Guidelines for Cancer Prevention on Colorectal Cancer Risk Público

Abstract

Background: Colorectal cancer (CRC) is the 3^rd most common cancer in men and women combined worldwide. Previous genome-wide association studies (GWAS) identified several common genetic variants associated with CRC risk. Additionally, observational studies demonstrated that healthy lifestyle choices are strongly association with colorectal neoplasms; however, little is known about joint effects of genetics and lifestyle on CRC risk.

Methods: A nested case control study including 1,462 CRC cases and 1,482 controls was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of more than 520,000 participants from 10 Western European countries. Odds ratios and 95% confidence intervals for the risk of CRC by categories of genetic risk score (GRS) alone and in combination with the WCRF/AICR score were estimated from unconditional logistic regression models, with adjustment for age at recruitment, sex, and study center.

Results:  Study participants with ≥18 CRC susceptibility loci had a statistically significantly higher risk for CRC (OR = 1.36; 95%: 1.09, 1.69) when compared to those with <14 loci. A high adherence to the WCRF/AICR recommendations was statistically significantly associated with a lower risk for CRC (OR = 0.79; 95%: 0.63, 0.98) compared to study participants with the least concordance. Joint analysis of the GRS and WCRF/AICR recommendation adherence suggested that better concordance with the WCRF/AICR recommendations is associated with lower CRC risk, regardless of genetic risk, so that individuals with low adherence to the WCRF/AICR recommendations and high genetic risk were at a statistically significantly higher risk of CRC compared to those with low genetic risk and high adherence to the WCRF/AICR recommendations (OR = 1.63; 95%: 1.12, 2.38).

Conclusion: Our study suggests that adherence to the WCRF/AICR recommendations is associated with lower CRC risk regardless of the genetic risk.

Table of Contents

Table of Contents

I.                  Background                                                                               1

a.     Colorectal Cancer Incidence and Mortality

b.     Colorectal Cancer Risk Factors

c.      Colorectal Cancer Screening

d.     Genetic Risk Alleles of Colorectal Cancer

e.      WCRF/AICR Recommendations

f.       Gene-Environment Interaction

II.               Methods                                                                                     11

III.            Results                                                                                         16       

IV.            Discussion                                                                                   18

V.               Future Directions                                                                      21

VI.            Citations                                                                                      22

VII.         Tables                                                                                           26

VIII.      Figures                                                                                         30

IX.            Appendices                                                                                 31

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Epidemiology - MPH & MSPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Biology, Genetics Health Sciences, Epidemiology Health Sciences, Public Health
Palabra Clave	Single Nucleotide Polymorphism Cancer Prevention Colorectal cancer Genetic Risk
Committee Chair / Thesis Advisor	Veronika Fedirko, Emory University

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