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| Home > Publications database > Colorectal Cancer Risk by Genetic Variants in Populations With and Without Colonoscopy History. |
| Journal Article | DKFZ-2021-00517 |
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2021
Oxford University Press
Oxford
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Please use a persistent id in citations: doi:10.1093/jncics/pkab008
Abstract: Polygenic risk scores (PRS), which are derived from results of large genome-wide association studies, are increasingly propagated for colorectal cancer (CRC) risk stratification. The majority of studies included in the large genome-wide association studies consortia were conducted in the United States and Germany, where colonoscopy with detection and removal of polyps has been widely practiced over the last decades. We aimed to assess if and to what extent the history of colonoscopy with polypectomy may alter metrics of the predictive ability of PRS for CRC risk.A PRS based on 140 single nucleotide polymorphisms was compared between 4939 CRC patients and 3797 control persons of the Darmkrebs: Chancen der Verhütung durch Screening (DACHS) study, a population-based case-control study conducted in Germany. Risk discrimination was quantified according to the history of colonoscopy and polypectomy by areas under the curves (AUCs) and their 95% confidence intervals (CIs). All statistical tests were 2-sided.AUCs and 95% CIs were higher among subjects without previous colonoscopy (AUC = 0.622, 95% CI = 0.606 to 0.639) than among those with previous colonoscopy and polypectomy (AUC = 0.568, 95% CI = 0.536 to 0.601; difference [Δ AUC] = 0.054, P = .004). Such differences were consistently seen in sex-specific groups (women: Δ AUC = 0.073, P = .02; men: Δ AUC = 0.046, P = .048) and age-specific groups (younger than 70 years: Δ AUC = 0.052, P = .07; 70 years or older: Δ AUC = 0.049, P = .045).Predictive performance of PRS may be underestimated in populations with widespread use of colonoscopy. Future studies using PRS to develop CRC prediction models should carefully consider colonoscopy history to provide more accurate estimates.
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