Table 4.
Sequential model comparison using 5-year sensitivity/specificity in the GERA European-ancestry participants. We presented the comparison across Model 1 (age and first-degree CRC family history), Model 2 (age, first-degree CRC family history, sex, and endoscopy history) and the PRS-enhanced model (age, first-degree CRC family history, sex, endoscopy history and polygenic risk score) on sensitivity and specificity with a risk threshold of 0.29% among GERA participants of European ancestry.
| Measure estimatea (95% CI) | Difference to PRS-enhanced model (95% CIb) | P-valueb | |
|---|---|---|---|
| All participants eligible for screening with agec 45–74 years | |||
| Sensitivity (177 individuals) | |||
| Model 1 | 93.8% (85.2%, 96.9%) | 0% (−5.2%, 3.9%) | p>0.99 |
| Model 2 | 90.4% (85.1%, 94.3%) | −3.4% (−7.5%, 0.8%) | p=0.11 |
| PRS-enhanced model | 93.8% (85.2%, 96.9%) | Reference | Reference |
| Specificity (52,890 individuals) | |||
| Model 1 | 16.4% (16.1%, 16.7%) | −14.6% (−15.0%, −14.2%) | p<0.001 |
| Model 2 | 20.1% (19.8%, 20.4%) | −10.9% (−11.3%, −10.6%) | p<0.001 |
| PRS-enhanced model | 31.0% (30.6%, 31.4%) | Reference | Reference |
| All participants with agec 40–49 years and having no endoscopy history | |||
| Sensitivity (11 individuals) | |||
| Model 1 | 9% (0%, 26%) | −55% (−86%, −25%) | p<0.001 |
| Model 2 | 36% (8%, 65%) | −27% (−54%, 0%) | p=0.04 |
| PRS-enhanced model | 64% (35%, 92%) | Reference | Reference |
| Specificity (6889 individuals) | |||
| Model 1 | 97% (96%, 97%) | 17% (16%, 18%) | p<0.001 |
| Model 2 | 79% (78%, 80%) | −1% (−2%, 0%) | p=0.05 |
| PRS-enhanced model | 80% (79%, 81%) | Reference | Reference |
| All participants: age 40–84 years | |||
| Sensitivity (309 individuals) | |||
| Model 1 | 96.1% (94.0%, 98.3%) | 0% (−2.7%, 2.7%) | p>0.99 |
| Model 2 | 94.2% (91.6%, 96.8%) | −1.9% (−4.4%, 0.3%) | p=0.09 |
| PRS-enhanced model | 96.1% (94.0%, 98.3%) | Reference | Reference |
| Specificity (65973 individuals) | |||
| Model 1 | 17.1% (16.8%, 17.4%) | −11.7% (−12.0%, −11.4%) | p<0.001 |
| Model 2 | 20.0% (19.7%, 20.4%) | −8.8% (−9.0%, −8.4%) | p<0.001 |
| PRS-enhanced model | 28.8% (28.4%, 29.1%) | Reference | Reference |
We dichotomized 5-year risks derived from each model to high- (>0.29%) and low-risk (≤0.29%) categories. The risk threshold of 0.29% represents the 5-year incidence CRC rate for average-risk individuals at age 50 based on SEER18 CRC incidence rates (2007–2015).
The 95% confidence intervals (CI) of the differences and the corresponding p-values were obtained by bootstrap resampling with 500 resamples.
Age at study entry.