Effect of a polygenic risk score in patients with late-onset, early-onset, familial, or hereditary colorectal cancer

Hannah Klinkhammer; Isabel Spier; Claudia Perne; Per Hoffmann; Reinhard Büttner; Evelin Schröck; Silke Redler; Arne Jahn; Marcus Franke; Gabriela Möslein; Matthias Kloor; Börge Schmidt; Deepak Vangala; Huu Phuc Nguyen; Andreas J. Forstner; Verena Steinke-Lange; Elke Holinski-Feder; Robert Hüneburg; Carlo Maj; Christoph Engel; Andreas Mayr; Stefan Aretz

doi:10.1093/jncics/pkag041

Key Points

To investigate how polygenic risk scores (PRS) affect colorectal cancer (CRC) risk in different onset groups and genetic backgrounds.
Analyzed the influence of PRS on CRC risk across late-onset and early-onset types.
Examined familial and hereditary cases of CRC.
Considered sample sizes and study design to explain variations in findings.
PRS significantly impacts CRC risk in unexplained early-onset and familial cases.
Effectiveness in Lynch syndrome individuals varies with gene penetrance and study design.
Non-significant trends observed suggest influence from subgroup sample sizes.

Implication

Observational study reveals the influence of polygenic risk scores on colorectal cancer in various onset types, suggesting the need for larger studies.

Abstract

PRS most strongly influences CRC risk in unexplained EOS- and F-CRC. The effect in LS individuals strongly depends on the penetrance of the altered gene and study design. Non-significant trends can partly be explained by the sample size of subgroups. Larger collaborative, prospective studies are needed to validate PRS for personalized CRC risk stratification.

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Cite This Study

Klinkhammer et al. (2026) studied this question.

synapsesocial.com/papers/69e07dc72f7e8953b7cbec35 https://doi.org/10.1093/jncics/pkag041

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Effect of a polygenic risk score in patients with late-onset, early-onset, familial, or hereditary colorectal cancer

Key Points

Implication

Abstract

Discussion

Cite This Study

Effect of a polygenic risk score in patients with late-onset, early-onset, familial, or hereditary colorectal cancer

Key Points

Implication

Abstract

Discussion

Cite This Study

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