Rare Germline Variants in ATM Predispose to Prostate Cancer : A PRACTICAL Consortium Study
PRACTICAL Consortium; 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 L J; Rathinakannan, Venkat; Sipeky, Csilla; Wiklund, Fredrik; Grönberg, Henrik; Aly, Markus; Isaacs, William B; Dickinson, Jo L; FitzGerald, Liesel M; Chua, Melvin L K; Nguyen-Dumont, Tu; Schaid, Daniel J; Southey, Melissa C; Eeles, Rosalind A; Kote-Jarai, Zsofia (2021)
PRACTICAL Consortium
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 L J
Rathinakannan, Venkat
Sipeky, Csilla
Wiklund, Fredrik
Grönberg, Henrik
Aly, Markus
Isaacs, William B
Dickinson, Jo L
FitzGerald, Liesel M
Chua, Melvin L K
Nguyen-Dumont, Tu
Schaid, Daniel J
Southey, Melissa C
Eeles, Rosalind A
Kote-Jarai, Zsofia
2021
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202108206667
https://urn.fi/URN:NBN:fi:tuni-202108206667
Kuvaus
Peer reviewed
Tiivistelmä
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.
Kokoelmat
- TUNICRIS-julkaisut [17109]