Breast cancer risk prediction using Tyrer-Cuzick algorithm with an 18-SNPs polygenic risk score in a European population with below-average breast cancer incidence.

Autor: Oblak T; Department of Surgical Oncology, Institute of Oncology Ljubljana, Zaloška cesta 2, 1000, Ljubljana, Slovenia; Medical Faculty, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia. Electronic address: toblak@onko-i.si., Škerl P; Department of Molecular Diagnostics, Institute of Oncology Ljubljana, Zaloška cesta 2, 1000, Ljubljana, Slovenia. Electronic address: pskerl@onko-i.si., Narang BJ; Institute for Biostatistics and Medical Informatics, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia; Department of Automatics, Jožef Stefan Institute, Biocybernetics and Robotics, Jamova cesta 39, Ljubljana, Slovenia; Faculty of Sport, University of Ljubljana, Gortanova 22, Ljubljana, Slovenia. Electronic address: benjamin.narang@ijs.si., Blagus R; Institute for Biostatistics and Medical Informatics, University of Ljubljana, Vrazov trg 2, 1000, Ljubljana, Slovenia; Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, Glagoljaška 8, 6000, Koper, Slovenia. Electronic address: rok.blagus@mf.uni-lj.si., Krajc M; Cancer Genetics Clinic, Institute of Oncology Ljubljana, Zaloška cesta 2, 1000, Ljubljana, Slovenia. Electronic address: mkrajc@onko-i.si., Novaković S; Department of Molecular Diagnostics, Institute of Oncology Ljubljana, Zaloška cesta 2, 1000, Ljubljana, Slovenia. Electronic address: snovakovic@onko-i.si., Žgajnar J; Department of Surgical Oncology, Institute of Oncology Ljubljana, Zaloška cesta 2, 1000, Ljubljana, Slovenia. Electronic address: jzgajnar@onko-i.si.
Jazyk: angličtina
Zdroj: Breast (Edinburgh, Scotland) [Breast] 2023 Dec; Vol. 72, pp. 103590. Date of Electronic Publication: 2023 Oct 12.
DOI: 10.1016/j.breast.2023.103590
Abstrakt: Goals: To determine whether an 18 single nucleotide polymorphisms (SNPs) polygenic risk score (PRS18) improves breast cancer (BC) risk prediction for women at above-average risk of BC, aged 40-49, in a Central European population with BC incidence below EU average.
Methods: 502 women aged 40-49 years at the time of BC diagnosis completed a questionnaire on BC risk factors (as per Tyrer-Cuzick algorithm) with data known at age 40 and before BC diagnosis. Blood samples were collected for DNA isolation. 250 DNA samples from healthy women aged 50 served as a control cohort. 18 BC-associated SNPs were genotyped in both groups and PRS18 was calculated. The predictive power of PRS18 to detect BC was evaluated using a ROC curve. 10-year BC risk was calculated using the Tyrer-Cuzick algorithm adapted to the Slovenian incidence rate (S-IBIS): first based on questionnaire-based risk factors and, second, including PRS18.
Results: The AUC for PRS18 was 0.613 (95 % CI 0.570-0.657). 83.3 % of women were classified at above-average risk for BC with S-IBIS without PRS18 and 80.7 % when PRS18 was included.
Conclusion: BC risk prediction models and SNPs panels should not be automatically used in clinical practice in different populations without prior population-based validation. In our population the addition of an 18SNPs PRS to questionnaire-based risk factors in the Tyrer-Cuzick algorithm in general did not improve BC risk stratification, however, some improvements were observed at higher BC risk scores and could be valuable in distinguishing women at intermediate and high risk of BC.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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