AUTHOR=Xie Peng , Wu Siqing , Kuo Zichong , Tian Huidong , He Qiangsheng , Li Yanfei , Mi Ningning , Hu Linmin , Zhao Haitong , Li Wenjing , Xia Bin , Yuan Jinqiu , Yang Kehu , Zhang Changhua , He Yulong TITLE=Association of modifiable lifestyle with colorectal cancer incidence and mortality according to metabolic status: prospective cohort study JOURNAL=Frontiers in Oncology VOLUME=Volume 13 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1162221 DOI=10.3389/fonc.2023.1162221 ISSN=2234-943X ABSTRACT=Background: Metabolic syndrome has been linked to an increased risk of colorectal cancer (CRC) incidence and mortality, but whether adopting a healthy lifestyle could attenuate the risk of CRC conferred by metabolic syndrome remains unclear. The aim of the study is to investigate the individual and joint effects of modifiable healthy lifestyle and metabolic health status on CRC incidence and mortality in the UK population. Methods: This prospective study included 328,236 individuals from the UK Biobank. An overall metabolic health status was assessed at baseline and categorized into “poor” and “ideal” based on the presence of metabolic syndrome. We estimated the association of the healthy lifestyle score (derived from 4 modifiable behaviors: smoking, alcohol consumption, diet, physical activity and categorized into “favorable,” “intermediate”, and “unfavorable”) with CRC incidence and mortality, stratified by metabolic health status. Results: During a median follow-up of 12.5 years, 3,852 CRC incidences and 1,076 deaths from CRC were newly identified. The risk of incident CRC and its mortality increased with the number of abnormal metabolic factors and decreased with healthy lifestyle score (P trend = 0.000). Poor metabolic status was associated with a greater incidence (HR = 1.24, 95% CI: 1.16 – 1.33) and mortality (HR = 1.24, 95% CI: 1.08 – 1.41) when compared with ideal metabolic status. An unfavorable healthy lifestyle was associated with an increased risk (HR = 1.25, 95% CI: 1.15 – 1.36) and mortality (HR = 1.36, 95% CI: 1.16 – 1.59) of CRC across all metabolic health status. Participants adopting an unfavorable healthy lifestyle with a poor metabolic status had a higher risk (HR = 1.56, 95% CI: 1.38 – 1.76) and mortality (HR = 1.75, 95% CI: 1.40 – 2.20) than those adopting a favorable healthy lifestyle with an ideal metabolic status. Conclusion: This study indicated that adherence to a healthy lifestyle could substantially reduce the burden of CRC regardless of the metabolic status. Behavioral lifestyle changes should be encouraged for CRC prevention even in participants with poor metabolic health.