Incidence of Germline Variants in Familial Bladder Cancer and Among Patients With Cancer Predisposition Syndromes.
Clin Genitourin Cancer
; 20(6): 568-574, 2022 12.
Article
em En
| MEDLINE
| ID: mdl-36127252
ABSTRACT
BACKGROUND:
The familial aggregation of bladder cancers has been observed, but the incidence and association of familial bladder cancer with germline pathogenic and likely pathogenic (P/LP) variants is unknown. PATIENTS ANDMETHODS:
A retrospective analysis was conducted of patients with bladder cancer treated at the Dana-Farber Cancer Institute to identify those with a first-degree relative with bladder cancer. A second cohort of patients referred to DFCI for suspicion of a cancer predisposition syndrome was analyzed for candidate P/LP germline variants. Descriptive statistics were generated.RESULTS:
Among 885 patients with bladder cancer, 38 patients (4.3%) had a family history of bladder cancer in a first-degree relative. No significant association of age of diagnosis was observed between patients with and without a first-degree family history of bladder cancer (P = .3). In the second cohort, 27 of 80 (34%) patients with bladder cancer evaluated for cancer predisposition syndromes harbored a P/LP germline variant. P/LP variants were identified most commonly in the following genes BRCA1 (n = 5), MSH2 (n = 5), MLH1 (n = 4), ATM (n = 3), and CHEK2 (n = 2). Of the 27 patients with identified germline P/LP variants, 20 (74%) had a family history of a tumor component syndrome in a first- or second-degree relative and 3 were subsequently diagnosed with another genetically-linked associated cancer.CONCLUSION:
Familial bladder cancer defined as bladder cancer in the proband and a first-degree relative, was present in 4.3% of patients with bladder cancer and was not associated with age of diagnosis. Additionally, among patients suspected to have a familial cancer syndrome, one-third harbored a germline P/LP variant. Further study of germline variants in patients with familial bladder cancer including somatic testing for loss of heterozygosity may provide insights regarding disease pathogenesis and inform therapy.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
/
Mutação em Linhagem Germinativa
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article