EAT-Lancet Diet Pattern, genetic risk, and risk of colorectal cancer: a prospective study from the UK Biobank.

Background: Diet and genetic risk are risk factors of colorectal cancer (CRC). The interaction between the EAT-Lancet diet and genetic variants on CRC risk remains unclear.
Objective: We aim to investigate the association between EAT-Lancet diet and CRC risk and to evaluate its combined effect with genetic risk on CRC risk.
Methods: We conducted a prospective cohort study involving 177,441 participants from the UK Biobank who completed 24-hour food recall questionnaires at least once. The EAT-Lancet Diet Index (ELD-I) was calculated using the dietary recall data to assess EAT-Lancet diet, and a polygenic risk score (PRS) was constructed by using 197 single-nucleotide polymorphisms (SNPs) to evaluate genetic risk. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models to assess the associations.
Results: During a median follow-up of 13.05 years, 2,016 participants developed CRC. Higher ELD-I was significantly associated with a reduced CRC risk (the highest versus the lowest HR: 0.87, 0.76-0.99). A significant additive interaction between PRS and ELD-I was identified on CRC risk (Relative Excess Risk due to Interaction: 0.142, 95% CI: 0.058-0.225). The ELD-I was significantly associated with reduced CRC risk in individuals with moderate but not low and high genetic risk, with HRs (95% CIs) of 0.76 (0.63-0.92), 0.84 (0.53-1.33), and 0.96 (0.76-1.20), respectively. Compared with participants with higher PRS and lower ELD-I, those with lower PRS and higher ELD-I showed a 75% reduction in CRC risk (HR: 0.25, 95% CI: 0.17-0.36).
Conclusion: The ELD-I could reduce 13% of CRC risk, especially in individuals with a moderate genetic risk. Individuals with high ELD-I and low PRS had the lowest CRC risk than those with low ELD-I and high PRS. These findings underscore the potential role of EAT-Lancet Diet in CRC prevention.
Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2025 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)