Background: Colorectal cancer (CRC) is the 3rd 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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|File download under embargo until 20 May 2021||2019-04-24||File download under embargo until 20 May 2021|