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

Abstract

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.

Figure 1.

Multivariable-adjusted 10-year cumulative incidence (left panel) and mortality (right panel) of colorectal cancer (CRC) and the corresponding absolute risk reduction (ARR) according to CRC risk score. CRC risk score (range = 0-8) was defined as the number of the 8 CRC high-risk factors: having a family history of CRC among the first-degree relatives, no regular use of aspirin (<2 tablets or times per week), tall stature (upper 50% of height in each cohort), overweight or obesity (body mass index ≥25.0 kg/m²), current smoker or past smoker with 5 or more pack-years, low physical activity (<30 min/d of moderate-to-vigorous intensity activity), heavy alcohol intake (≥1 drink [14 g alcohol] per day for women and ≥2 drinks per day for men), and unhealthy diet (meeting <3 of the 6 dietary recommendations by the World Cancer Research Fund/American Institute for Cancer Research Report 2018, which included red meat <0.5 serving per day, processed meat <0.2 serving per day, dietary fiber ≥30 g/d, dairy products ≥3 servings per day, whole grains ≥48 g/d or account for at least one-half of total grains, and calcium supplement use). Trend in the ARRs across CRC risk scores was examined by regressing the multivariable-adjusted cumulative risk on baseline colonoscopy screening status and CRC risk score as well as their product term, whose P value was derived as the P_trend. The tests were 2-sided. Error bars indicate 95% confidence intervals.

Figure 2.

Multivariable-adjusted 10-year cumulative mortality of colorectal cancer (CRC) by subsite and corresponding absolute risk reduction according to CRC risk score. CRC risk score (range = 0-8) was defined as the number of the 8 CRC high-risk factors: having a family history of CRC among the first-degree relatives, no regular use of aspirin (<2 tablets or times per week), tall stature (upper 50% of height in each cohort), overweight or obesity (body mass index ≥25.0 kg/m²), current smoker or past smoker with 5 or more pack-years, low physical activity (<30 min/d of moderate-to-vigorous intensity activity), heavy alcohol intake (≥1 drink [14 g alcohol] per day for women and ≥2 drinks per day for men), and unhealthy diet (meeting <3 of the 6 dietary recommendations by the World Cancer Research Fund/American Institute for Cancer Research Report 2018, which included red meat <0.5 serving per day, processed meat <0.2 serving per day, dietary fiber ≥30 g/d, dairy products ≥3 servings per day, whole grains ≥48 g/d or account for at least one-half of total grains, and calcium supplement use). Trend in the ARRs across CRC risk scores was examined by regressing the multivariable-adjusted cumulative risk on baseline colonoscopy screening status and CRC risk score as well as their product term, whose P value was derived as the P_trend. The tests were 2-sided. Error bars indicate 95% confidence intervals.

Figure 3.

Multivariable-adjusted 10-year cumulative incidence of colorectal cancer (CRC) by age in all participants and according to CRC risk score. The crossed solid straight lines indicate the 10-year cumulative incidence of CRC of 0.47% in the whole study population at age 45 years, when CRC screening is recommended to start. The crossed dash straight lines indicate the corresponding incidence of 0.68% at age 50 years. Individuals with a CRC risk score of 0-2, 3, 4, 5, and 6-7 reached the age 45 years threshold risk at age 51 years, 48 years, 45 years, 42 years, and 38 years, respectively. CRC risk score (range = 0-8) was defined as the number of the 8 CRC high-risk factors: having a family history of CRC among the first-degree relatives, no regular use of aspirin (<2 tablets or times per week), tall stature (upper 50% of height in each cohort), overweight or obesity (body mass index ≥25.0 kg/m²), current smoker or past smoker with 5 or more pack-years, low physical activity (<30 min/d of moderate-to-vigorous intensity activity), heavy alcohol intake (≥1 drink [14 g alcohol] per day for women and ≥2 drinks per day for men), and unhealthy diet (meeting <3 of the 6 dietary recommendations by the World Cancer Research Fund/American Institute for Cancer Research Report 2018, which included red meat <0.5 serving per day, processed meat <0.2 serving per day, dietary fiber ≥30 g/d, dairy products ≥3 servings per day, whole grains ≥48 g/d or account for at least one-half of total grains, and calcium supplement use).