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 and Methods
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.
Keywords
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Article info
Publication history
Published online: August 28, 2022
Accepted:
August 20,
2022
Received in revised form:
August 17,
2022
Received:
October 23,
2021
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
