Rare Germline Variants in ATM Predispose to Prostate Cancer: A PRACTICAL Consortium Study.
Eur Urol Oncol
; 4(4): 570-579, 2021 08.
Article
en En
| MEDLINE
| ID: mdl-33436325
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, ANDPARTICIPANTS:
We analysed next-generation sequencing data from 13 PRACTICAL study groups comprising 5560 cases and 3353 controls of European ancestry. OUTCOME MEASUREMENTS AND STATISTICALANALYSIS:
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 ANDLIMITATIONS:
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. PATIENTSUMMARY:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias de la Próstata
/
Predisposición Genética a la Enfermedad
Límite:
Humans
/
Male
Idioma:
En
Revista:
Eur Urol Oncol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Reino Unido