Effectiveness of colorectal cancer screening integrating non-genetic and genetic risk: a prospective study based on UK Biobank data

Abstract

Objective: Few studies have evaluated the benefits of colorectal cancer (CRC) screening integrating both non-genetic and genetic risk factors. Here, we aimed to integrate an existing non-genetic risk model (QCancer-10) and a 139-variant polygenic risk score to evaluate the effectiveness of screening on CRC incidence and mortality. Methods: We applied the integrated model to calculate 10-year CRC risk for 430,908 participants in the UK Biobank, and divided the participants into low-, intermediate-, and high-risk groups. We calculated the screening-associated hazard ratios (HRs) and absolute risk reductions (ARRs) for CRC incidence and mortality according to risk stratification. Results: During a median follow-up of 11.03 years and 12.60 years, we observed 5,158 CRC cases and 1,487 CRC deaths, respectively. CRC incidence and mortality were significantly lower among screened than non-screened participants in both the intermediate- and high-risk groups [incidence: HR: 0.87, 95% confidence interval (CI): 0.81–0.94; 0.81, 0.73–0.90; mortality: 0.75, 0.64–0.87; 0.70, 0.58–0.85], which composed approximately 60% of the study population. The ARRs (95% CI) were 0.17 (0.11–0.24) and 0.43 (0.24–0.61), respectively, for CRC incidence, and 0.08 (0.05–0.11) and 0.24 (0.15–0.33), respectively, for mortality. Screening did not significantly reduce the relative or absolute risk of CRC incidence and mortality in the low-risk group. Further analysis revealed that screening was most effective for men and individuals with distal CRC among the intermediate to high-risk groups. Conclusions: After integrating both genetic and non-genetic factors, our findings provided priority evidence of risk-stratified CRC screening and valuable insights for the rational allocation of health resources.

Keywords

• colorectal cancer
• screening
• polygenic risk score
• incidence
• mortality