Healthy Plant-Based Diet and Cancer Risk Across Genetic and Phenotypic Adiposity Levels

Peggy Ler, Hwayoung Noh, Jihye Kim, Heinz Freisling

Background: Adiposity is a known risk factor for several cancers, whereas dietary patterns, such as adherence to a healthy plant-based diet, may be protective. Whether genetic susceptibility to adiposity and phenotypic adiposity influence the association between plant-based diet and cancer risk remains unclear.

Objectives: We examined whether the genetic susceptibility to adiposity, polygenic score for body mass index (PGSBMI), and phenotypic BMI modify the association between a healthy plant-based diet and incident cancer risk.

Methods: Data from the UK Biobank (n = 195,098; 20,078 incident cancer cases) were analyzed. A healthy plant-based diet index (hPDI) was derived from 17 food groups assessed using 24-hour dietary recalls and standardised (per 1 SD). BMI was categorised into normal weight (BMI 18.5 – 24.9 kg/m2), overweight (BMI 25 – 29.9 kg/m2), and obesity (BMI ≥ 30 kg/m2). PGSBMI was standardized. Cox proportional hazards models with attained age as the underlying timescale were used to estimate the association between hPDI and cancer incidence. Models were adjusted for sex, smoking, education, ethnicity, alcohol consumption, assessment centre, and Townsend Deprivation Index. Models, including PGSBMI, were additionally adjusted for genetic principal components. All continuous variables were evaluated for nonlinearity using spline terms. Effect modification by PGSBMI and BMI was tested by including an interaction term between hPDI and PGSBMI or between hPDI and BMI. Statistical significance of the interaction was assessed using likelihood-ratio tests comparing nested models with and without interaction terms (p-interaction).

Results: hPDI was associated with lower cancer incidence in models adjusted for PGSBMI [Hazard ratios (HR): 0.98; 95% confidence intervals (95% CI): 0.97 – 0.99], BMI (HR: 0.99; 95% CI: 0.97 – 0.99), and in models including both adiposity measures (HR: 0.99; 95% CI: 0.97 – 0.99). PGSBMI was associated with higher cancer incidence (HR: 1.02; 95% CI: 1.01 – 1.03), with the association attenuated and no longer statistical significant when additionally adjusted for BMI. Compared with normal weight, overweight (HR: 1.11; 95% CI: 1.08 – 1.15) and obesity (HR: 1.16; 95% CI: 1.12 – 1.21) were associated with higher cancer incidence, and the estimates remained statistically significant after mutual adjustment for PGSBMI. There was no evidence of interaction between hPDI and PGSBMI (p-interaction = 0.49) or BMI (p-interaction =0.30).

Conclusions: A healthy plant-based diet was associated with a modestly lower risk of incident cancer independent of genetic susceptibility and phenotypic adiposity. While genetic predisposition to higher BMI, phenotypic presentation of overweight and obesity were each associated with higher cancer risk, we did not find evidence that they modify the hPDI-cancer link. A healthy plant-based diet may be beneficial across genetic and phenotypic adiposity levels.

Acknowledgements: This work was supported by the National Research Foundation of Korea funded by the Korea Government  (Ministry of Science and ICT; grant number  RS-2025–00513735 to Jihye Kim).