Plant-based dietary patterns, genetic predisposition and risk of colorectal cancer: a prospective study from the UK Biobank

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.

Keywords: Colorectal cancer; Diet quality; Plant-based diet indices; Polygenic risk score; UK Biobank.

Fig. 1

Associations of PDI, hPDI, and uPDI with risk of CRC incidence. The models adjusted for age (continuous), sex (female, male), ethnicity (White, mixed, Asian, Black, Chinese, others, or unknown), education (college or university, vocational qualification, upper secondary, lower secondary, others, or unknown), Townsend deprivation index (in quintiles), body mass index (< 18.5, 18.5–24.9, 25-29.9, or ≥ 30 kg/m²), alcohol frequency (daily or almost daily, 3 or 4 times a week, 1 or 2 times a week, 1 to 3 times a month, special occasions only, never, or unknown), smoking status (never, former, current, or unknown), physical activity (low, moderate, high, or unknown), total energy intake (continuous), polygenic risk score for CRC (continuous), first 10 principal components of ancestry (in Units, continuous), and genotype measurement batch (continuous). CI confidence interval, CRC colorectal cancer, hPDI healthful plant-based diet index, HR hazard ratio, PDI plant-based diet index, uPDI unhealthful plant-based diet index

Fig. 2

Joint Associations of PDI, hPDI, and uPDI and PRS with risk of CRC incidence. The models adjusted for age (continuous), sex (female, male), ethnicity (White, mixed, Asian, Black, Chinese, others, or unknown), education (college or university, vocational qualification, upper secondary, lower secondary, others, or unknown), Townsend deprivation index (in quintiles), body mass index (< 18.5, 18.5–24.9, 25-29.9, or ≥ 30 kg/m²), alcohol frequency (daily or almost daily, 3 or 4 times a week, 1 or 2 times a week, 1 to 3 times a month, special occasions only, never, or unknown), smoking status (never, former, current, or unknown), physical activity (low, moderate, high, or unknown), total energy intake (continuous), first 10 principal components of ancestry (in Units, continuous), and genotype measurement batch (continuous). CI confidence interval, CRC colorectal cancer, hPDI healthful plant-based diet index, HR hazard ratio, PDI plant-based diet index, uPDI unhealthful plant-based diet index

Fig. 3

Associations of PDI, hPDI, and uPDI with risk of CRC mortality. The models adjusted for age (continuous), sex (female, male), ethnicity (White, mixed, Asian, Black, Chinese, others, or unknown), education (college or university, vocational qualification, upper secondary, lower secondary, others, or unknown), Townsend deprivation index (in quintiles), body mass index (< 18.5, 18.5–24.9, 25-29.9, or ≥ 30 kg/m2), alcohol frequency (daily or almost daily, 3 or 4 times a week, 1 or 2 times a week, 1 to 3 times a month, special occasions only, never, or unknown), smoking status (never, former, current, or unknown), physical activity (low, moderate, high, or unknown), total energy intake (continuous), polygenic risk score for CRC (continuous), first 10 principal components of ancestry (in Units, continuous), and genotype measurement batch (continuous). CI confidence interval, CRC colorectal cancer, hPDI healthful plant-based diet index, HR hazard ratio, PDI plant-based diet index, uPDI unhealthful plant-based diet index