Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/179930
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: https://doi.org/10.3390/cancers13153857 |
It is part of: | Cancers, 2021, vol. 13, num. 15, p. 3857 |
URI: | http://hdl.handle.net/2445/179930 |
Related resource: | https://doi.org/10.3390/cancers13153857 |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
cancers-13-03857.pdf | 912.13 kB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License