Healthy dietary patterns, genetic risk, and gastrointestinal cancer incident risk: a large-scale prospective cohort study.

BACKGROUND:Dietary patterns have been associated with several cancers, especially gastrointestinal cancer (GIC). However, whether a healthy dietary pattern could modify the risk of GIC among people with different genetic backgrounds is not clear. OBJECTIVE:The objective of the study was to investigate how dietary patterns and genetic susceptibility contribute to the risk of GIC independently and jointly. METHODS:This large-scale prospective cohort study included 105,463 participants in UK Biobank who were aged 40-72 y and cancer-free at baseline. Dietary intake (Oxford WebQ) was used to calculate dietary pattern scores including dietary approach to stop hypertension (DASH) score and healthful plant-based diet index (hPDI). Genetic risk was quantified by a polygenic risk score (PRS) comprising 129 known GIC-associated loci. Cox proportional hazards regression was performed to estimate the associations of dietary patterns and PRS with GIC incidence after adjusting for potential confounders. RESULTS:Over a median follow-up of 11.70 y, 1,661 participants were diagnosed with GIC. DASH and hPDI were associated with 20% and 36% reductions, respectively, in GIC risk. Low PRS was associated with a 30 % decrease in GIC risk (HR: 0.70; 95% CI: 0.62, 0.79). Participants with healthy dietary scores at high-genetic risk had a lower GIC risk with HR of 0.77 (95% CI: 0.60, 0.98) for DASH and 0.66 (95% CI: 0.52, 0.84) for hPDI than those with unhealthy dietary score. Participants with both high-dietary score and low-genetic risk showed the lowest risk of GIC, with HR of 0.58 (95% CI: 0.45, 0.75) for DASH and 0.45 (95% CI: 0.34, 0.58) for hPDI. CONCLUSIONS:Adherence to DASH and hPDI were associated with a lower risk of some gastrointestinal cancers, and these 2 dietary patterns may partly compensate for genetic predispositions to cancer. Our results advance the development of precision medicine strategies that consider both dietary patterns and genetics to improve gastrointestinal health.