A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Rare Germline Variants in ATM Predispose to Prostate Cancer: A PRACTICAL Consortium Study
Tekijät: Karlsson Questa, Brook Mark N, Dadaev Tokhir, Wakerell Sarah, Saunders Edward J, Muir Kenneth, Neal David E, Giles Graham G, MacInnis Robert J, Thibodeau Stephen N, McDonnell Shannon K, Cannon-Albright Lisa, Teixeira Manuel R, Paulo Paula, Cardoso Marta, Huff Chad, Li Donghui, Yao Yu, Scheet Paul, Permuth Jennifer B, Stanford Janet L, Dai James Y, Ostrander Elaine A, Cussenot Olivier, Cancel-Tassin Géraldine, Hoegel Josef, Herkommer Kathleen, Schleutker Johanna, Tammela Teuvo LJ, Rathinakannan Venkat, Sipeky Csilla, Wiklund Fredrik, Grönberg Henrik, Aly Markus, Isaacs William B, Dickinson Jo L, FitzGerald Liesel M, Chua Melvin LK, Nguyen-Dumont Tu, PRACTICAL Consortium, Schaid Daniel J, Southey Melissa C, Eeles Rosalind A, Kote-Jarai Zsofia
Kustantaja: Elsevier
Julkaisuvuosi: 2021
Journal: European Urology Oncology
Tietokannassa oleva lehden nimi: EUROPEAN UROLOGY ONCOLOGY
Lehden akronyymi: EUR UROL ONCOL
Vuosikerta: 4
Numero: 4
Aloitussivu: 570
Lopetussivu: 579
Sivujen määrä: 10
eISSN: 2588-9311
DOI: https://doi.org/10.1016/j.euo.2020.12.001
Verkko-osoite: https://www.sciencedirect.com/science/article/pii/S2588931120302091?via%3Dihub
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/66908601
Background: Germline ATM mutations are suggested to contribute to predisposition to prostate cancer (PrCa). Previous studies have had inadequate power to estimate variant effect sizes.
Objective: To precisely estimate the contribution of germline ATM mutations to PrCa risk.
Design, setting, and participants: A We analysed next-generation sequencing data from 13 PRACTICAL study groups comprising 5560 cases and 3353 controls of European ancestry.
Outcome measurements and statistical analysis: Variant Call Format files were harmonised, annotated for rare ATM variants, and classified as tier 1 (likely pathogenic) or tier 2 (potentially deleterious). Associations with overall PrCa risk and clinical subtypes were estimated.
Results and limitations: PrCa risk was higher in carriers of a tier 1 germline ATM variant, with an overall odds ratio (OR) of 4.4 (95% confidence interval [CI]: 2.0-9.5). There was also evidence that PrCa cases with younger age at diagnosis (<65 yr) had elevated tier 1 variant frequencies (p(difference) = 0.04). Tier 2 variants were also associated with PrCa risk, with an OR of 1.4 (95% CI: 1.1-1.7).
Conclusions: Carriers of pathogenic ATM variants have an elevated risk of developing PrCa and are at an increased risk for earlier-onset disease presentation. These results provide information for counselling of men and their families.
Patient summary: In this study, we estimated that men who inherit a likely pathogenic mutation in the ATM gene had an approximately a fourfold risk of developing prostate cancer. In addition, they are likely to develop the disease earlier. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
