Risk stratification for early-onset colorectal cancer using a combination of genetic and environmental risk scores: An international multi-center study Journal Article


Authors: Archambault, A. N.; Jeon, J.; Lin, Y.; Thomas, M.; Harrison, T. A.; Bishop, D. T.; Brenner, H.; Casey, G.; Chan, A. T.; Chang-Claude, J.; Figueiredo, J. C.; Gallinger, S.; Gruber, S. B.; Gunter, M. J.; Guo, F.; Hoffmeister, M.; Jenkins, M. A.; Keku, T. O.; Le Marchand, L.; Li, L.; Moreno, V.; Newcomb, P. A.; Pai, R.; Parfrey, P. S.; Rennert, G.; Sakoda, L. C.; Lee, J. K.; Slattery, M. L.; Song, M.; Win, A. K.; Woods, M. O.; Murphy, N.; Campbell, P. T.; Su, Y. R.; Lansdorp-Vogelaar, I.; Peterse, E. F. P.; Cao, Y.; Zeleniuch-Jacquotte, A.; Liang, P. S.; Du, M.; Corley, D. A.; Hsu, L.; Peters, U.; Hayes, R. B.
Article Title: Risk stratification for early-onset colorectal cancer using a combination of genetic and environmental risk scores: An international multi-center study
Abstract: Background The incidence of colorectal cancer (CRC) among individuals aged younger 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 3486 cases and 3890 controls aged younger 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 SD of ERS = 1.14, 95% confidence interval [CI] = 1.08 to 1.20; odds ratio per SD of PRS = 1.59, 95% CI = 1.51 to 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615 to 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.
Keywords: guidelines; mutations; adults; identification; genome-wide association; metaanalysis; susceptibility loci
Journal Title: JNCI: Journal of the National Cancer Institute
Volume: 114
Issue: 4
ISSN: 0027-8874
Publisher: Oxford University Press  
Date Published: 2022-04-01
Start Page: 528
End Page: 539
Language: English
ACCESSION: WOS:000761987900001
DOI: 10.1093/jnci/djac003
PROVIDER: wos
PMCID: PMC9002285
PUBMED: 35026030
Notes: Article -- Source: Wos
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  1. Mengmeng   Du
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