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Title: Non-Lynch Familial and Early-Onset Colorectal Cancer Explained by Accumulation of Low-Risk Genetic Variants
Author: Mur, Pilar
Bonifaci, Núria
Díez Villanueva, Anna
Munté, Elisabet
Alonso Aguado, Maria Henar
Obón Santacana, Mireia
Aiza, Gemma
Navarro García, Matilde
Piñol, Virginia
Brunet, Joan
Tomlinson, Ian
Capellá, G. (Gabriel)
Moreno Aguado, Víctor
Valle, Laura
Keywords: Càncer colorectal
Malalties hereditàries
Colorectal Cancer
Genetic disorders
Issue Date: 31-Jul-2021
Publisher: MDPI AG
Abstract: A large proportion of familial and/or early-onset cancer patients do not carry pathogenic variants in known cancer predisposing genes. We aimed to assess the contribution of previously validated low-risk colorectal cancer (CRC) alleles to familial/early-onset CRC (fCRC) and to serrated polyposis. We estimated the association of CRC with a 92-variant-based weighted polygenic risk score (wPRS) using 417 fCRC patients, 80 serrated polyposis patients, 1077 hospital-based incident CRC patients, and 1642 controls. The mean wPRS was significantly higher in fCRC than in controls or sporadic CRC patients. fCRC patients in the highest (20th) wPRS quantile were at four-fold greater CRC risk than those in the middle quantile (10th). Compared to low-wPRS fCRC, a higher number of high-wPRS fCRC patients had developed multiple primary CRCs, had CRC family history, and were diagnosed at age ≥50. No association with wPRS was observed for serrated polyposis. In conclusion, a relevant proportion of mismatch repair (MMR)-proficient fCRC cases might be explained by the accumulation of low-risk CRC alleles. Validation in independent cohorts and development of predictive models that include polygenic risk score (PRS) data and other CRC predisposing factors will determine the implementation of PRS into genetic testing and counselling in familial and early-onset CRC.
Note: Reproducció del document publicat a:
It is part of: Cancers, 2021, vol. 13, num. 15, p. 3857
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Clíniques)

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