Associations between BMI, polygenic risk score for BMI, lifestyle and the risk of upper gastrointestinal cancer

Abstract

Abstract Objective To investigate the risk of upper gastrointestinal (UG) cancer associated with BMI across different polygenic risk score for BMI (PRSBMI), and to investigate whether healthy lifestyles could attenuate this risk. Methods The joint association between BMI and PRSBMI [low risk: quintile 1–2; intermediate risk: quintile 3–4; high risk: quintile 5] on UG cancer risk were evaluated among 386,427 participants from the UK Biobank cohort, and stratified associations were further investigated according to the scores of lifestyle [favorable lifestyle: 0–1 score; intermediate lifestyle: 2–3 scores; unfavorable lifestyle: 4 scores]. Results UG cancer significantly associated with BMI, PRSBMI, and numbers of unfavorable lifestyles in dose-response manners, and the adjusted hazard ratios [HRs(95%CI)] were 1.12(0.99–1.27) and 1.39(1.21–1.60) for intermediate and high BMI, 1.15(1.02–1.29) and 1.20(1.05–1.38) for intermediate and high PRSBMI, and 1.40(1.22–1.60) and 2.17(1.79–2.64) for intermediate and unfavorable lifestyles, respectively. Moreover, higher risk was observed for high BMI but low PRSBMI than high PRSBMI but low BMI. After stratifying by lifestyle, there was no obvious interaction and joint association of BMI and PRSBMI with UG cancer risk among participants with favorable lifestyle, while intermediate and unfavorable lifestyle further increased the risk, with HRs ranging from 1.37 to 4.95. Conclusions Generally, both high BMI and PRSBMI were associated with increased risk of UG cancer. Moreover, favorable lifestyle could attenuate the increased UG cancer risks associated with high BMI and/or high genetic predisposition of excess BMI. Adopting healthy lifestyles and keeping healthy weight are recommended to reduce UG cancer risk.