The 3V score and joint associations of low ultra-processed food, biodiverse and plant-based diets on colorectal cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Abstract

Background: Diet may modify colorectal cancer risk. We investigated the associations of three dietary patterns, ultra-processed food (UPF) consumption, healthy plant-based food consumption, and food biodiversity, separately and combined into a "3V" score with risk of colorectal cancer.

Methods: This study used data from the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which recruited participants between 1992, and 2000, from 23 centres in ten European countries. The 3V score was developed by standardising and summing the healthy plant diet index (hPDI) and dietary species richness per year (DSR) and subtracting UPF (Nova category 4) intake in % g/day. Associations with colorectal cancer risk were assessed among 450,111 middle-aged participants of the EPIC cohort using multivariable-adjusted Cox regression models. Independent associations of each 3V component were assessed using mutually adjusted models. Data-driven thresholds were applied to assess adherence to the 3V components, set at the minimum value of the fourth quintile for hPDI, DSR and low UPF.

Findings: During mean (standard deviation (SD)) follow-up of 14.9 (4) years, absolute colorectal cancer rates were 8.59 and 10.37 cases/10,000 person-years for the highest and lowest quintiles of the 3V score, respectively. Inverse associations were found for colorectal (hazard ratio (HR) comparing highest vs lowest quintile: 0.84; 95% confidence interval (CI): 0.76-0.94), colon (HR: 0.82; 95% CI: 0.72-0.93), and distal colon cancer (HR: 0.81; 95% CI: 0.67-0.99), with significant linear trends observed across quintiles. UPF intake was positively associated with colon cancer risk (HR per 1 SD increment: 1.06; 95% CI: 1.02-1.11) when mutually adjusted for the other 3V components. Adherence to low UPF, high hPDI, and high DSR was inversely associated with colorectal (HR: 0.73; 95% CI: 0.61-0.88), colon (HR: 0.72; 95% CI: 0.57-0.91), and rectal cancer (HR: 0.65; 95% CI: 0.46-0.91) compared to adhering to none.

Interpretation: Adherence to the 3V diet is associated with lower risk of colorectal cancers.

Funding: Cancer Research UK, World Cancer Research Fund.

Keywords: Colorectal cancer; Dietary risk factors; Food biodiversity; Food processing; Prospective cohort.

Fig. 1

Forest plot of the associations between dietary scores—UPF intake, DSR, hPDI, and the 3V score (calculated as SD(DSR) + SD(hPDI)–SD(UPF))—and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 450,111). Panel A indicates the hazard ratios (HR) for a 1 SD increase in UPF intake, DSR, hPDI and the 3V score, while panel B indicates the HR comparing each dietary score quintile (Q2, Q3, Q4, Q5) to the lowest quintile (Q1) for UPF intake, DSR, hPDI, and the 3V score. The composite 3V score was constructed by standardising three key dietary exposures: UPF intake (% g/day), hPDI (18–90 points), and DSR (species/year) to account for differences in their units of measurement. Each participant's 3V score was calculated by summing the standardised values of DSR and hPDI, and subtracting the standardised value of UPF intake, assuming equal importance for each dimension (i.e., 3V score = SD (DSR) + SD (hPDI)–SD (UPF)). Regression models were separately fitted for each dietary score, and the same model adjustments were applied for each score. The models were stratified for centre, sex (male, female), and age at recruitment (1-year intervals, timescale) and adjusted for education (none or primary school completed; secondary school; technical or professional school; longer education including university degree; not specified), smoking status and intensity of smoking (never; current, 1–15 cigarettes/day; current, 16–25 cigarettes/day; current, 26+ cigarettes/day; former, quit ≤10 years; former, quit 11–20 years; former, quit 20+ years; current, pipe/cigar/occasionally; unknown), physical activity (Cambridge index: inactive; moderately inactive; moderately active; active; missing), height (cm), body mass index (kg/m²), alcohol intake at recruitment (g/day), and energy intake (kcal/day). N = 450,111, with 6162 cases of colorectal cancer, 3841 cases of colon cancer, 1726 cases of distal colon cancer, 1856 cases of proximal colon cancer, and 2058 cases of rectal cancer. CI, Confidence Interval; DSR, Dietary Species Richness; hPDI, healthful Plant-Based Diet Index; SD, Standard Deviation; UPF, Ultra-Processed Foods.

Fig. 2

Forest Plot of the associations between UPF intake, DSR, hPDI and cumulative 3V score (calculated as DSR (0 or 1), hPDI (0 or 1), and UPF (1 or 0)) and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 450,111). Panel A indicates the associations of dietary scores when mutually adjusted. Panel B indicates the association of the cumulative 3V score (HR per criterion met). The models were stratified for centre, sex (male, female), and age at recruitment (1-year intervals, timescale) and adjusted for education (none or primary school completed; secondary school; technical or professional school; longer education including university degree; not specified), smoking status and intensity of smoking (never; current, 1–15 cigarettes/day; current, 16–25 cigarettes/day; current, 26+ cigarettes/day; former, quit ≤10 years; former, quit 11–20 years; former, quit 20+ years; current, pipe/cigar/occasionally; unknown), physical activity (Cambridge index: inactive; moderately inactive; moderately active; active; missing), height (cm), body mass index (kg/m²), alcohol intake at recruitment (g/day), and energy intake (kcal/day). Thresholds for the cumulative 3V score were set at the minimum values of the fourth quintile (Q4) for each dietary component: 13.96% g/day for UPF (scored as 1 for lower consumption and 0 for higher), 58 points for hPDI, and 73 species/year for DSR, with participants in Q4 and Q5 receiving a score of 1 for both. These scores were then summed to calculate adherence to the combination of 3V components, giving a theoretical range for the cumulative 3V score of 0–3 criteria met (cumulative 3V score = DSR (0 or 1) + hPDI (0 or 1) + UPF (0 or 1)). n = 450,111, with 6162 cases of colorectal cancer, 3841 cases of colon cancer, 1726 cases of distal colon cancer, 1856 cases of proximal colon cancer, and 2058 cases of rectal cancer. CI, Confidence Interval; DSR, Dietary Species Richness; HR, Hazard Ratio; hPDI, healthful Plant-Based Diet Index; SD, Standard Deviation; UPF, Ultra-Processed Foods.

Fig. 3

Associations between UPF, DSR, and hPDI thresholds and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 450,111). All the associations were compared to the scenario where none of the recommendations were met. Thresholds for the cumulative 3V score were set at the minimum values of the fourth quintile (Q4) for each dietary component: 13.96% g/day for UPF (scored as 1 for lower consumption and 0 for higher), 58 points for hPDI, and 73 species/year for DSR, with participants in Q4 and Q5 receiving a score of 1 for both. The models were stratified for centre, sex (male, female), and age at recruitment (1-year intervals, timescale) and adjusted for education (none or primary school completed; secondary school; technical or professional school; longer education including university degree; not specified), smoking status and intensity of smoking (never; current, 1–15 cigarettes/day; current, 16–25 cigarettes/day; current, 26+ cigarettes/day; former, quit ≤10 years; former, quit 11–20 years; former, quit 20+ years; current, pipe/cigar/occasionally; unknown), physical activity (Cambridge index: Inactive; moderately inactive; moderately active; active; missing), height (cm), body mass index (kg/m²), alcohol intake at recruitment (g/day), and energy intake (kcal/day). The numbers of events/total participants by cancer site and threshold, among those who meet the threshold for each criterion, are as follows: For colorectal cancer, low UPF (2593/168,947), high hPDI (1353/103,157), high DSR (1933/136,185), low UPF and high hPDI (2059/157,897), low UPF and high DSR (1867/130,325), high hPDI and high DSR (1187/90,121), and low UPF, high hPDI, and high DSR (1500/111,739). For colon, low UPF (1623/167,919), high hPDI (855/102,643), high DSR (1207/135,426), low UPF and high hPDI (1328/157,105), low UPF and high DSR (1139/129,544), high hPDI and high DSR (751/89,664), and low UPF, high hPDI, and high DSR (958/111,158). For distal colon, low UPF (734/167,030), high hPDI (368/102,156), high DSR (524/134,743), low UPF and high hPDI (599/156,376), low UPF and high DSR (515/128,920), high hPDI and high DSR (337/89,250), and low UPF, high hPDI, and high DSR (437/110,637). For proximal colon, low UPF (791/167,087), high hPDI (433/102,221), high DSR (604/134,823), low UPF and high hPDI (654/156,431), low UPF and high DSR (546/128,951), high hPDI and high DSR (372/89,285), and low UPF, high hPDI, and high DSR (466/110,666). For rectal cancer, low UPF (884/167,180), high hPDI (453/102,241), high DSR (644/134,863), low UPF and high hPDI (660/156,437), low UPF and high DSR (640/129,045), high hPDI and high DSR (393/89,306), and low UPF, high hPDI, and high DSR (478/110,678). CI, Confidence Interval; DSR, Dietary Species Richness; HR, Hazard Ratio; hPDI, healthful Plant-Based Diet Index; SD, Standard Deviation; UPF, Ultra-Processed Foods.