dc.contributor.author | Karlsson, Q | |
dc.contributor.author | Brook, MN | |
dc.contributor.author | Dadaev, T | |
dc.contributor.author | Wakerell, S | |
dc.contributor.author | Saunders, EJ | |
dc.contributor.author | Muir, K | |
dc.contributor.author | Neal, DE | |
dc.contributor.author | Giles, GG | |
dc.contributor.author | MacInnis, RJ | |
dc.contributor.author | Thibodeau, SN | |
dc.contributor.author | McDonnell, SK | |
dc.contributor.author | Cannon-Albright, L | |
dc.contributor.author | Teixeira, MR | |
dc.contributor.author | Paulo, P | |
dc.contributor.author | Cardoso, M | |
dc.contributor.author | Huff, C | |
dc.contributor.author | Li, D | |
dc.contributor.author | Yao, Y | |
dc.contributor.author | Scheet, P | |
dc.contributor.author | Permuth, JB | |
dc.contributor.author | Stanford, JL | |
dc.contributor.author | Dai, JY | |
dc.contributor.author | Ostrander, EA | |
dc.contributor.author | Cussenot, O | |
dc.contributor.author | Cancel-Tassin, G | |
dc.contributor.author | Hoegel, J | |
dc.contributor.author | Herkommer, K | |
dc.contributor.author | Schleutker, J | |
dc.contributor.author | Tammela, TLJ | |
dc.contributor.author | Rathinakannan, V | |
dc.contributor.author | Sipeky, C | |
dc.contributor.author | Wiklund, F | |
dc.contributor.author | Grönberg, H | |
dc.contributor.author | Aly, M | |
dc.contributor.author | Isaacs, WB | |
dc.contributor.author | Dickinson, JL | |
dc.contributor.author | FitzGerald, LM | |
dc.contributor.author | Chua, MLK | |
dc.contributor.author | Nguyen-Dumont, T | |
dc.contributor.author | PRACTICAL Consortium, | |
dc.contributor.author | Schaid, DJ | |
dc.contributor.author | Southey, MC | |
dc.contributor.author | Eeles, RA | |
dc.contributor.author | Kote-Jarai, Z | |
dc.date.accessioned | 2021-01-25T14:54:00Z | |
dc.date.issued | 2021-01-09 | |
dc.identifier.citation | European urology oncology, 2021 | |
dc.identifier.issn | 2588-9311 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4314 | |
dc.identifier.eissn | 2588-9311 | |
dc.identifier.doi | 10.1016/j.euo.2020.12.001 | |
dc.description.abstract | 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 (<65 yr) had elevated tier 1 variant frequencies (pdifference = 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. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | PRACTICAL Consortium | |
dc.title | Rare Germline Variants in ATM Predispose to Prostate Cancer: A PRACTICAL Consortium Study. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-12-01 | |
rioxxterms.versionofrecord | 10.1016/j.euo.2020.12.001 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-01-09 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | European urology oncology | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/18/19 Starting Cohort | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/18/19 Starting Cohort | |
pubs.publication-status | Published | |
pubs.embargo.terms | Not known | |
icr.researchteam | Oncogenetics | |
dc.contributor.icrauthor | Brook, Mark | |
dc.contributor.icrauthor | Saunders, Edward | |
dc.contributor.icrauthor | Eeles, Rosalind | |
dc.contributor.icrauthor | Kote-Jarai, Zsofia | |