EAT-Lancet diet pattern, genetic risk, and risk of colorectal cancer: a prospective study from the UK Biobank

Abstract

Background: Diet and genetic risk are risk factors for colorectal cancer (CRC). The interaction between the EAT (Lancet Commission on healthy diets from sustainable food systems)-Lancet diet and genetic variants on CRC risk remains unclear.

Objectives: 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-h 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 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 y, 2,016 participants developed CRC. Higher ELD-I was significantly associated with a reduced CRC risk (the highest compared with the lowest HR: 0.87, 95% CI: 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).

Conclusions: 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.

Keywords: EAT-Lancet Diet Index; colorectal cancer; dietary pattern; genetic risk; prospective cohort study.