Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome

Background: Polygenic risk scores (PRSs) have been used to stratify colorectal cancer (CRC) risk in the general population, whereas its role in Lynch syndrome (LS), the most common type of hereditary CRC, is still conflicting. We aimed to assess the ability of PRS to refine CRC risk prediction in Eu...

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Autores: Dueñas, Nuria, Klinkhammer, Hannah, Bonifaci Cano, Núria, Spier, Isabel, Mayr, Andreas, Hassanin, Emadeldin, Díez Villanueva, Anna, Moreno Aguado, Víctor, Pineda, Marta, Maj, Carlo, Capellà, Gabriel, Aretz, Stefan, Brunet, Joan
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/209225
Acceso en línea:https://hdl.handle.net/2445/209225
Access Level:acceso abierto
Palabra clave:Càncer colorectal
Malalties hereditàries
Malalties neonatals
Colorectal cancer
Genetic diseases
Neonatal diseases
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spelling Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndromeDueñas, NuriaKlinkhammer, HannahBonifaci Cano, NúriaSpier, IsabelMayr, AndreasHassanin, EmadeldinDíez Villanueva, AnnaMoreno Aguado, VíctorPineda, MartaMaj, CarloCapellà, GabrielAretz, StefanBrunet, JoanCàncer colorectalMalalties hereditàriesMalalties neonatalsColorectal cancerGenetic diseasesNeonatal diseasesBackground: Polygenic risk scores (PRSs) have been used to stratify colorectal cancer (CRC) risk in the general population, whereas its role in Lynch syndrome (LS), the most common type of hereditary CRC, is still conflicting. We aimed to assess the ability of PRS to refine CRC risk prediction in European-descendant individuals with LS. Methods: 1465 individuals with LS (557 MLH1, 517 MSH2/EPCAM, 299 MSH6 and 92 PMS2) and 5656 CRC-free population-based controls from two independent cohorts were included. A 91-SNP PRS was applied. A Cox proportional hazard regression model with 'family' as a random effect and a logistic regression analysis, followed by a meta-analysis combining both cohorts were conducted. Results: Overall, we did not observe a statistically significant association between PRS and CRC risk in the entire cohort. Nevertheless, PRS was significantly associated with a slightly increased risk of CRC or advanced adenoma (AA), in those with CRC diagnosed <50 years and in individuals with multiple CRCs or AAs diagnosed <60 years. Conclusion: The PRS may slightly influence CRC risk in individuals with LS in particular in more extreme phenotypes such as early-onset disease. However, the study design and recruitment strategy strongly influence the results of PRS studies. A separate analysis by genes and its combination with other genetic and non-genetic risk factors will help refine its role as a risk modifier in LS.BMJ Publishing Group2024202420232024info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion28 p.application/pdfhttps://hdl.handle.net/2445/209225Articles publicats en revistes (Ciències Clíniques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1136/jmg-2023-109344Journal of Medical Genetics, 2023, vol. 60, num.11, p. 1044-1051https://doi.org/10.1136/jmg-2023-109344cc-by-nc (c) Dueñas, Nuria et al., 2023http://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2092252026-05-29T05:05:01Z
dc.title.none.fl_str_mv Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome
title Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome
spellingShingle Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome
Dueñas, Nuria
Càncer colorectal
Malalties hereditàries
Malalties neonatals
Colorectal cancer
Genetic diseases
Neonatal diseases
title_short Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome
title_full Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome
title_fullStr Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome
title_full_unstemmed Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome
title_sort Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome
dc.creator.none.fl_str_mv Dueñas, Nuria
Klinkhammer, Hannah
Bonifaci Cano, Núria
Spier, Isabel
Mayr, Andreas
Hassanin, Emadeldin
Díez Villanueva, Anna
Moreno Aguado, Víctor
Pineda, Marta
Maj, Carlo
Capellà, Gabriel
Aretz, Stefan
Brunet, Joan
author Dueñas, Nuria
author_facet Dueñas, Nuria
Klinkhammer, Hannah
Bonifaci Cano, Núria
Spier, Isabel
Mayr, Andreas
Hassanin, Emadeldin
Díez Villanueva, Anna
Moreno Aguado, Víctor
Pineda, Marta
Maj, Carlo
Capellà, Gabriel
Aretz, Stefan
Brunet, Joan
author_role author
author2 Klinkhammer, Hannah
Bonifaci Cano, Núria
Spier, Isabel
Mayr, Andreas
Hassanin, Emadeldin
Díez Villanueva, Anna
Moreno Aguado, Víctor
Pineda, Marta
Maj, Carlo
Capellà, Gabriel
Aretz, Stefan
Brunet, Joan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer colorectal
Malalties hereditàries
Malalties neonatals
Colorectal cancer
Genetic diseases
Neonatal diseases
topic Càncer colorectal
Malalties hereditàries
Malalties neonatals
Colorectal cancer
Genetic diseases
Neonatal diseases
description Background: Polygenic risk scores (PRSs) have been used to stratify colorectal cancer (CRC) risk in the general population, whereas its role in Lynch syndrome (LS), the most common type of hereditary CRC, is still conflicting. We aimed to assess the ability of PRS to refine CRC risk prediction in European-descendant individuals with LS. Methods: 1465 individuals with LS (557 MLH1, 517 MSH2/EPCAM, 299 MSH6 and 92 PMS2) and 5656 CRC-free population-based controls from two independent cohorts were included. A 91-SNP PRS was applied. A Cox proportional hazard regression model with 'family' as a random effect and a logistic regression analysis, followed by a meta-analysis combining both cohorts were conducted. Results: Overall, we did not observe a statistically significant association between PRS and CRC risk in the entire cohort. Nevertheless, PRS was significantly associated with a slightly increased risk of CRC or advanced adenoma (AA), in those with CRC diagnosed <50 years and in individuals with multiple CRCs or AAs diagnosed <60 years. Conclusion: The PRS may slightly influence CRC risk in individuals with LS in particular in more extreme phenotypes such as early-onset disease. However, the study design and recruitment strategy strongly influence the results of PRS studies. A separate analysis by genes and its combination with other genetic and non-genetic risk factors will help refine its role as a risk modifier in LS.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/209225
url https://hdl.handle.net/2445/209225
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1136/jmg-2023-109344
Journal of Medical Genetics, 2023, vol. 60, num.11, p. 1044-1051
https://doi.org/10.1136/jmg-2023-109344
dc.rights.none.fl_str_mv cc-by-nc (c) Dueñas, Nuria et al., 2023
http://creativecommons.org/licenses/by-nc/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc (c) Dueñas, Nuria et al., 2023
http://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 28 p.
application/pdf
dc.publisher.none.fl_str_mv BMJ Publishing Group
publisher.none.fl_str_mv BMJ Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Clíniques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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