Association Between Cardiovascular Risk Factors and Colorectal Cancer: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

Background: Emerging data have suggested colorectal cancer (CRC) often coexists with cardiovascular diseases, but whether cardiovascular risk factors play a role in CRC remains unclear. We performed a systematic review and meta-analysis of prospective cohort studies to better illustrate the associations between cardiovascular risk factors and CRC. Methods: We searched EMBASE, MEDLINE and Web of Science databases from inception up to June 14, 2020. Studies were included if they evaluated the association between at least one of cardiovascular risk factors and CRC incidence, contained sufficient data to obtain relative risk (RR) and 95% confidence interval (CI). We performed separate meta-analyses for each cardiovascular risk factor using random-effect model. Findings: Data from 84 prospective cohort studies, reporting 52, 348, 827 individuals and 384, 973 incident cases were included in the analysis. Overall, the risk of CRC was 1.31(95% CI, 1.21-1.42) for obesity, 1.14 (95% CI, 1.08-1.20) for per 5 kg/m 2 increase in BMI, 1.18 (95% CI, 1.14-1.23) for former smoker, 1.20 (95% CI, 1.11-1.30) for current smoker, 1.25 (95% CI, 1.16-1.35) for diabetes, 1.07 (95% CI, 1.02-1.12) for hypertension. The summary RRs of CRC for the highest versus lowest quartiles of total cholesterol, triglyceride, low-density lipoprotein were 1.12 (95% CI, 1.03-1.22), 1.18 (95% CI, 1.04-1.35), 0.85 (95% CI, 0.62-1.17) respectively and the pooled RR for the lowest versus highest quartile of high-density lipoprotein was 1.14 (95% CI, 1.02-1.28). Interpretation: Unfavorable cardiovascular risk factors are associated with increased risk of CRC. Although the potential mechanisms are still under investigation, these findings may provide novel insight into the primary and secondary prevention of CRC. Registration: PROSPERO CRD42020175537. Funding Statement: This work was supported by National Natural Science Foundation of China (Grant No. 81300279, 81741067 and 81600260), Guangdong Natural Science Foundation (Grant No. 2016A030313815, 2016A030313210, 2017A030313464 and 2018A030310655), Science and Technology Planning Project of Guangdong Province (Grant No. 2015A020212029 and 2017A020215174), Science and Technology Program of Guangzhou (Grant No. 201707010419 and 201804010050), Medical Scientific Research Foundation of Guangdong Province (Grant No. A2018343 and A2019063), Guangdong Basic and Applied Basic Research Foundation (Grant No. 2020A1515011161), High-level Hospital Construction Project (Grant No. DFJH201803, KJ012019099 and DFJH201923), the Fundamental Research Funds for the Central Universities (Grant No. D2180600), the project of Kelin new star of the First Affiliated Hospital of Sun Yat-Sen University (Grant No. Y50186), and the Fundamental Research Funds for the Central Universities in Sun Yat-Sen University (Grant No.18ykpy08). Declaration of Interests: The authors declare that they have no potential conflicts of interest.