The best linear unbiased prediction (BLUP) method as a tool to estimate the lifetime risk of pancreatic ductal adenocarcinoma in high-risk individuals with no known pathogenic germline variants.

Autor: Cristina-Marianini-Rios; Department of Agricultural Economics, Statistics and Business Management, Universidad Politécnica de Madrid, Madrid, Spain., Sanchez MEC; Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9, 100, Madrid, 28034, Spain., de Paredes AGG; Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9, 100, Madrid, 28034, Spain.; Gastroenterology and Hepatology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain., Rodríguez M; Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9, 100, Madrid, 28034, Spain.; Medical Oncology Department, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, 28034, Spain.; The Biomedical Research Network in Cancer (CIBERONC), Av. Monforte de Lemos, 3-5. Pabellón 11. Planta 0, Madrid, 28029, Spain.; University of Alcalá, Madrid, Spain., Barreto E; Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9, 100, Madrid, 28034, Spain.; The Biomedical Research Network in Cancer (CIBERONC), Av. Monforte de Lemos, 3-5. Pabellón 11. Planta 0, Madrid, 28029, Spain.; University of Alcalá, Madrid, Spain., López JV; Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9, 100, Madrid, 28034, Spain., Fuentes R; Medical Oncology Department, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, 28034, Spain., Beltrán MM; Radiology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain., Sanjuanbenito A; Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9, 100, Madrid, 28034, Spain.; The Biomedical Research Network in Cancer (CIBERONC), Av. Monforte de Lemos, 3-5. Pabellón 11. Planta 0, Madrid, 28029, Spain.; Pancreatic and Biliopancreatic Surgery Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain., Lobo E; Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9, 100, Madrid, 28034, Spain.; Pancreatic and Biliopancreatic Surgery Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain., Caminoa A; Department of Pathology, Hospital Universitario Ramón y Cajal, Madrid, 28034, Spain., Ruz-Caracuel I; Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9, 100, Madrid, 28034, Spain.; The Biomedical Research Network in Cancer (CIBERONC), Av. Monforte de Lemos, 3-5. Pabellón 11. Planta 0, Madrid, 28029, Spain.; Department of Pathology, Hospital Universitario Ramón y Cajal, Madrid, 28034, Spain., Durán SL; Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9, 100, Madrid, 28034, Spain.; Gastroenterology and Hepatology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain., Olcina JRF; Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9, 100, Madrid, 28034, Spain.; Gastroenterology and Hepatology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain., Blázquez J; Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9, 100, Madrid, 28034, Spain.; Radiology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain., Sequeros EV; Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9, 100, Madrid, 28034, Spain.; Gastroenterology and Hepatology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.; The Biomedical Research Network in Cancer (CIBERONC), Av. Monforte de Lemos, 3-5. Pabellón 11. Planta 0, Madrid, 28029, Spain., Carrato A; Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9, 100, Madrid, 28034, Spain.; The Biomedical Research Network in Cancer (CIBERONC), Av. Monforte de Lemos, 3-5. Pabellón 11. Planta 0, Madrid, 28029, Spain.; University of Alcalá, Madrid, Spain.; Pancreatic Cancer Europe, Brussels, Belgium., Ávila JCM; Department of Agricultural Economics, Statistics and Business Management, Universidad Politécnica de Madrid, Madrid, Spain. jc.martinez.avila@upm.es., Earl J; Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9, 100, Madrid, 28034, Spain. julie.earl@live.co.uk.; The Biomedical Research Network in Cancer (CIBERONC), Av. Monforte de Lemos, 3-5. Pabellón 11. Planta 0, Madrid, 28029, Spain. julie.earl@live.co.uk.
Jazyk: angličtina
Zdroj: Familial cancer [Fam Cancer] 2024 Aug; Vol. 23 (3), pp. 233-246. Date of Electronic Publication: 2024 May 23.
DOI: 10.1007/s10689-024-00397-w
Abstrakt: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the Western world. The number of diagnosed cases and the mortality rate are almost equal as the majority of patients present with advanced disease at diagnosis. Between 4 and 10% of pancreatic cancer cases have an apparent hereditary background, known as hereditary pancreatic cancer (HPC) and familial pancreatic cancer (FPC), when the genetic basis is unknown. Surveillance of high-risk individuals (HRI) from these families by imaging aims to detect PDAC at an early stage to improve prognosis. However, the genetic basis is unknown in the majority of HRIs, with only around 10-13% of families carrying known pathogenic germline mutations. The aim of this study was to assess an individual's genetic cancer risk based on sex and personal and family history of cancer. The Best Linear Unbiased Prediction (BLUP) methodology was used to estimate an individual's predicted risk of developing cancer during their lifetime. The model uses different demographic factors in order to estimate heritability. A reliable estimation of heritability for pancreatic cancer of 0.27 on the liability scale, and 0.07 at the observed data scale as obtained, which is different from zero, indicating a polygenic inheritance pattern of PDAC. BLUP was able to correctly discriminate PDAC cases from healthy individuals and those with other cancer types. Thus, providing an additional tool to assess PDAC risk HRI with an assumed genetic predisposition in the absence of known pathogenic germline mutations.
(© 2024. The Author(s).)
Databáze: MEDLINE
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