Search

Objective: Low body fat and high physical activity levels are key lifestyle factors in cancer prevention, but the interplay of abdominal obesity and physical activity on cancer risk remains unknown. We explored individual and joint associations of waist circumference and physical activity with cancer risk., Methods: Using UK Biobank data (n=315 457), we categorised individuals according to WHO guideline thresholds for waist circumference and self-reported physical activity levels. Multivariable-adjusted Cox regression was used to estimate HRs and 95% CIs of total cancer. The reference group comprised individuals with recommended levels of waist circumference (<88 cm for women and <102 cm for men) and physical activity (>10 metabolic equivalent of task hours/week). Furthermore, we estimated the proportion of cancers attributable to abdominal obesity and insufficient physical activity., Results: During a median follow-up period of 11 years (3 321 486 person-years), 29 710 participants developed any type of cancer. Participants not meeting the WHO guideline on waist circumference had increased cancer risk, even when sufficiently physically active according to the WHO (HR 1.11, 95% CI 1.08 to 1.15). Similarly, individuals not achieving the WHO guideline for physical activity showed an elevated risk, even if they were abdominally lean (HR 1.04, 95% CI 1.01 to 1.07). Not adhering to either guideline yielded the strongest increase in risk (HR 1.15, 95% CI 1.11 to 1.19). We estimated that abdominal obesity coupled with insufficient physical activity could account for 2.0% of UK Biobank cancer cases., Conclusion: Adherence to both WHO guidelines for waist circumference and physical activity is essential for cancer prevention; meeting just one of these guidelines is insufficient., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Previous prediction models for adiposity gain have not yet achieved sufficient predictive ability for clinical relevance. We investigated whether traditional and genetic factors accurately predict adiposity gain., Methods: A 5-year gain of ≥5% in body mass index (BMI) and waist-to-hip ratio (WHR) from baseline were predicted in mid-late adulthood individuals (median of 55 years old at baseline). Proportional hazards models were fitted in 245,699 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to identify robust environmental predictors. Polygenic risk scores (PRS) of 5 proxies of adiposity [BMI, WHR, and three body shape phenotypes (PCs)] were computed using genetic weights from an independent cohort (UK Biobank). Environmental and genetic models were validated in 29,953 EPIC participants., Findings: Environmental models presented a remarkable predictive ability (AUC BMI : 0.69, 95% CI: 0.68-0.70; AUC WHR : 0.75, 95% CI: 0.74-0.77). The genetic geographic distribution for WHR and PC1 (overall adiposity) showed higher predisposition in North than South Europe. Predictive ability of PRSs was null (AUC: ∼0.52) and did not improve when combined with environmental models. However, PRSs of BMI and PC1 showed some prediction ability for BMI gain from self-reported BMI at 20 years old to baseline observation (early adulthood) (AUC: 0.60-0.62)., Interpretation: Our study indicates that environmental models to discriminate European individuals at higher risk of adiposity gain can be integrated in standard prevention protocols. PRSs may play a robust role in predicting adiposity gain at early rather than mid-late adulthood suggesting a more important role of genetic factors in this life period., Funding: French National Cancer Institute (INCA&#95;N°2019-176) 1220, German Research Foundation (BA 5459/2-1), Instituto de Salud Carlos III (Miguel Servet Program CP21/00058)., Competing Interests: Declaration of interests L.M. discloses that an immediate family member holds stocks in Novo Nordisk. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)