Abstract
BACKGROUND: Plant-based dietary patterns may affect colorectal cancer (CRC) related outcomes, while risks differ in the quality of plant foods. We aimed to examine the association of plant-based diet quality with risks of CRC incidence and mortality and whether this association was modified by genetic risk. METHODS: This prospective cohort study included 186,675 participants free of cancer when the last dietary recall was completed. We calculated three plant-based diet indices (PDIs), i.e., the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI) representing adherence to plant-based diets with diverse quality. Genetic risk was characterized using a weighted polygenic risk score (PRS), capturing overall risk variants associated with CRC. Hazard ratios (HR) and 95% confidential intervals (CI) were estimated by the cause-specific Cox proportional hazards model. RESULTS: Over a follow-up of 9.5 years, 2163 cases and 466 deaths from CRC were documented. The HR of CRC incidence was 0.88 (95% CI, 0.81-0.96) and 0.91 (95% CI, 0.84-0.99) per 10-score increase in PDI and hPDI, respectively. Compared to the lowest quartile, PDI, hPDI, and uPDI in the highest quartile were associated with a 13% decrease, a 15% decrease, and a 14% increase in risk of incident CRC, respectively. We found a joint association of genetic risk and PDIs with incident CRC, with the highest hazard observed in those carrying higher PRS and adhering to lower-quality PDIs. The inverse association of PDI and hPDI with CRC mortality was pronounced in males. CONCLUSIONS: Our results suggested that better adherence to overall and healthful plant-based diets was associated with a lower risk of CRC, whereas an unhealthful plant-based diet was associated with a higher CRC risk. Consumption of a higher-quality plant-based diet combined with decreased genetic risk conferred less susceptibility to CRC. Our findings highlighted the importance of food quality when adhering to a plant-based dietary pattern for CRC prevention in the general population.