Long-Term Colorectal Cancer Incidence and Mortality After Colonoscopy Screening According to Individuals' Risk Profiles

Background: It remains unknown whether the benefit of colonoscopy screening against colorectal cancer (CRC) and the optimal age to start screening differ by CRC risk profile.

Methods: Among 75 873 women and 42 875 men, we defined a CRC risk score (0-8) based on family history, aspirin, height, body mass index, smoking, physical activity, alcohol, and diet. We calculated colonoscopy screening-associated hazard ratios and absolute risk reductions (ARRs) for CRC incidence and mortality and age-specific CRC cumulative incidence according to risk score. All statistical tests were 2-sided.

Results: During a median of 26 years of follow-up, we documented 2407 CRC cases and 874 CRC deaths. Although the screening-associated hazard ratio did not vary by risk score, the ARRs in multivariable-adjusted 10-year CRC incidence more than doubled for individuals with scores 6-8 (ARR = 0.34%, 95% confidence interval [CI] = 0.26% to 0.42%) compared with 0-2 (ARR = 0.15%, 95% CI = 0.12% to 0.18%, Ptrend < .001). Similar results were found for CRC mortality (ARR = 0.22%, 95% CI = 0.21% to 0.24% vs 0.08%, 95% CI = 0.07% to 0.08%, Ptrend < .001). The ARR in mortality of distal colon and rectal cancers was fourfold higher for scores 6-8 than 0-2 (distal colon cancer: ARR = 0.08%, 95% CI = 0.07% to 0.08% vs 0.02%, 95% CI = 0.02% to 0.02%, Ptrend < .001; rectal cancer: ARR = 0.08%, 95% CI = 0.08% to 0.09% vs 0.02%, 95% CI = 0.02% to 0.03%, Ptrend < .001). When using age 45 years as the benchmark to start screening, individuals with risk scores of 0-2, 3, 4, 5, and 6-8 attained the threshold CRC risk level (10-year cumulative risk of 0.47%) at age 51 years, 48 years, 45 years, 42 years, and 38 years, respectively.

Conclusions: The absolute benefit of colonoscopy screening is more than twice higher for individuals with the highest than lowest CRC risk profile. Individuals with a high- and low-risk profile may start screening up to 6-7 years earlier and later, respectively, than the recommended age of 45 years.