Chemoprevention of colorectal cancer in general population and high-risk population: a systematic review and network meta-analysis

Chin Med J (Engl). 2023 Apr 5;136(7):788-798. doi: 10.1097/CM9.0000000000002514.

Abstract

Background: Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents.

Methods: We searched PubMed, Embase, and the Cochrane Library for studies published in English until October 31, 2021 that fit our inclusion criteria. We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents (low-dose aspirin [Asp], high-dose Asp, cyclooxygenase-2 inhibitors [coxibs], calcium, vitamin D, folic acid, ursodeoxycholic acid [UDCA], estrogen, and progesterone, alone or in combination) for preventing colorectal adenoma and CRC. Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study.

Results: Thirty-two randomized controlled trials (278,694 participants) comparing 13 different interventions were included. Coxibs significantly reduced the risk of colorectal adenoma (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.44-0.79, six trials involving 5486 participants), advanced adenoma (RR: 0.63, 95% CI: 0.43-0.92, four trials involving 4723 participants), and metachronous adenoma (RR: 0.58, 95% CI: 0.43-0.79, five trials involving 5258 participants) compared with placebo. Coxibs also significantly increased the risk of severe adverse events (RR: 1.29, 95% CI: 1.13-1.47, six trials involving 7109 participants). Other interventions, including Asp, folic acid, UDCA, vitamin D, and calcium, did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo.

Conclusions: Considering the balance between benefits and harms, regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence. Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence.

Registration: PROSPERO, No. CRD42022296376.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adenoma* / drug therapy
  • Adenoma* / prevention & control
  • Aspirin
  • Calcium
  • Chemoprevention
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / prevention & control
  • Cyclooxygenase 2 Inhibitors
  • Humans
  • Network Meta-Analysis
  • Vitamin D
  • Vitamins

Substances

  • Cyclooxygenase 2 Inhibitors
  • Calcium
  • Vitamins
  • Aspirin
  • Vitamin D