Association of screening status, polygenic risk score, and environmental risk factors with colorectal cancer incidence and mortality risks.

Whether screening can attenuate the influence of genetic risk and environmental risk factors for colorectal cancer (CRC) mortality risk remains unknown. This study is to investigate the association of the screening history, genetic risk, and environmental risk factors with CRC incidence and mortality risks using UK Biobank data. Screening history was associated with lower CRC incidence (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.58-0.69) and mortality risk (HR: 0.56, 95% CI: 0.49-0.63). Compared with the HRs of participants with a low genetic risk, low environmental risk, and no screening history, the HRs of participants with a high genetic risk, high environmental risk, and no screening history were 3.42 (95% CI: 2.76-4.24) for CRC incidence and 3.36 (95% CI: 2.48-4.56) for CRC mortality. In contrast, the HRs of participants with a high genetic risk and no screening history, but a low environmental risk, were 1.92 (95% CI: 1.55-2.36) for CRC incidence and 1.88 (95% CI: 1.39-2.53) for CRC mortality. Furthermore, the HRs of participants with a high genetic risk and a low environmental risk, but a screening history were 1.62 (95% CI: 1.15-2.28) for CRC incidence and 1.77 (95% CI: 1.08-2.89) for CRC mortality. Participants benefited more substantially from screenings for CRC mortality than for CRC incidence risk. A higher environmental risk was associated with higher risk of CRC incidence and mortality within each category of genetic risk. These findings emphasize the importance of CRC screening and identifying environmental factors to reduce CRC incidence and mortality risks.