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Rare Germline Variants in ATM Predispose to Prostate Cancer: A PRACTICAL Consortium Study

Title: Rare Germline Variants in ATM Predispose to Prostate Cancer: A PRACTICAL Consortium Study
Authors: Karlsson, Q; Brook, MN; Dadaev, T; Wakerell, S; Saunders, EJ; Muir, K; Neal, DE; Giles, GG; MacInnis, RJ; Thibodeau, SN; McDonnell, SK; Cannon-Albright, L; Teixeira, MR; Paulo, P; Cardoso, M; Huff, C; Li, D; Yao, Y; Scheet, P; Permuth, JB; Stanford, JL; Dai, JY; Ostrander, EA; Cussenot, O; Cancel-Tassin, G; Hoegel, J; Herkommer, K; Schleutker, J; Tammela, TLJ; Rathinakannan, V; Sipeky, C; Wiklund, F; Grönberg, H; Aly, M; Isaacs, WB; Dickinson, JL; FitzGerald, LM; Chua, MLK; Nguyen-Dumont, T; Schaid, DJ; Southey, MC; Eeles, RA; Kote-Jarai, Z
Publisher Information: ELSEVIER
Publication Year: 2021
Collection: The University of Melbourne: Digital Repository
Description: 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: 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 (
Document Type: article in journal/newspaper
Language: English
ISSN: 2588-9311
Relation: https://hdl.handle.net/11343/287128
Availability: https://hdl.handle.net/11343/287128
Rights: https://creativecommons.org/licenses/by-nc-nd/4.0 ; CC BY-NC-ND
Accession Number: edsbas.FEE8F4B6
Database: BASE