Background: In addition to adiposity, lifestyle factors such as poor diet, low physical activity, alcohol intake and smoking are noted to be associated with the development of colorectal cancer (CRC). This study aims to investigate the association and dose-response relationship between adherence to a healthy lifestyle and CRC risk. Methods: A systematic literature search was conducted in MEDLINE and EMBASE for studies examining multiple lifestyle factors with risk of CRC, incident colorectal adenoma (CRA), and CRC-specific mortality through June 2021 without restrictions on language or study design. Meta-analysis was performed to pool hazard ratios using random-effects model. Subgroup analyses were performed based upon study and sample characteristics. Random-effects dose-response analysis was also conducted for CRC risk to assess the effect of each additional healthy lifestyle factor. Results: A total of 28 studies (18 cohort studies, eight case-control studies, and two cross-sectional study) were included. When comparing subjects with the healthiest lifestyle to those with the least healthy lifestyle, the pooled HR was statistically significant for CRC (0.52, 95% CI 0.44-0.63), colon cancer (0.54, 95% CI 0.44-0.67), rectal cancer (0.51, 95% CI 0.37-0.70), CRA (0.39, 95% CI 0.29-0.53), and CRC-specific mortality (0.65, 95% CI 0.52-0.81). The pooled HR for CRC was 0.91 (95% CI: 0.88-0.94) for each increase in the number of healthy lifestyles. The inverse association between healthy lifestyle and CRC risk was consistently observed in all subgroups (HR ranging from 0.26 to 0.86). Conclusions: Adoption of a higher number of healthy lifestyles is associated with lower risk of CRC, CRA, and CRC-specific mortality. Promoting healthy lifestyle could reduce the burden of CRC. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=231398, identifier CRD42021231398.
colorectal, lifestyle, dose-response, incident, index, prevention