Risk Stratification for Early-Onset Colorectal Cancer Using a Combination of Genetic and Environmental Risk Scores: An International Multi-Center Study
Menée à partir de données portant sur 3 486 patients atteints d'un cancer colorectal et 3 890 témoins (âge : inférieur à 50 ans), cette étude multicentrique évalue la performance de modèles prédictifs combinant deux systèmes de score, l'un basé sur 16 facteurs liés au mode de vie et à l'environnement, l'autre sur la présence de 141 variants, pour identifier les patients susceptibles de développer précocement un cancer colorectal
Background : Incidence of colorectal cancer (CRC) among individuals aged less than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS), of 141 variants.
Methods : Relying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3,486 cases and 3,890 controls aged less than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve.
Results : Increasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per standard deviation of ERS = 1.14, 95% confidence interval [CI] = 1.08, 1.20; odds ratio per standard deviation of PRS = 1.59, 95% CI = 1.51, 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615, 0.647). Based on absolute risks, we can expect 26 excess cases per 10,000 men and 21 per 10,000 women, among those scoring at the 90th percentile for both risk scores.
Conclusions : Personal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes.
Journal of the National Cancer Institute , résumé, 2021