Polygenic scores in cancer

Since the publication of the first genome-wide association study for cancer in 2007, thousands of common alleles that are associated with the risk of cancer have been identified. The relative risk associated with individual variants is small and of limited clinical significance. However, the combine...

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Vydáno v:Nature reviews. Cancer Ročník 23; číslo 9; s. 619 - 630
Hlavní autoři: Yang, Xin, Kar, Siddhartha, Antoniou, Antonis C, Pharoah, Paul D P
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Nature Publishing Group 01.09.2023
Témata:
Alleles
Cancer
Clinical Relevance
Clinical trials
Genome-wide association studies
Genome-Wide Association Study
Genomes
Humans
Neoplasms - genetics
Prediction models
Reviews
Therapeutic applications
ISSN:1474-175X, 1474-1768, 1474-1768
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Shrnutí:Since the publication of the first genome-wide association study for cancer in 2007, thousands of common alleles that are associated with the risk of cancer have been identified. The relative risk associated with individual variants is small and of limited clinical significance. However, the combined effect of multiple risk variants as captured by polygenic scores (PGSs) may be much greater and therefore provide risk discrimination that is clinically useful. We review the considerable research efforts over the past 15 years for developing statistical methods for PGSs and their application in large-scale genome-wide association studies to develop PGSs for various cancers. We review the predictive performance of these PGSs and the multiple challenges currently limiting the clinical application of PGSs. Despite this, PGSs are beginning to be incorporated into clinical multifactorial risk prediction models to stratify risk in both clinical trials and clinical implementation studies.
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ISSN:1474-175X
1474-1768
1474-1768
DOI:10.1038/s41568-023-00599-x