Inherited Germline Cancer Susceptibility Gene Variants in Individuals with Non-Muscle-Invasive Bladder Cancer.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
03 10 2022
03 10 2022
Historique:
received:
30
03
2022
revised:
07
06
2022
accepted:
12
07
2022
pubmed:
15
7
2022
medline:
5
10
2022
entrez:
14
7
2022
Statut:
ppublish
Résumé
Identification of inherited germline variants can guide personalized cancer screening, prevention, and treatment. Pathogenic and likely pathogenic (P/LP) germline variants in cancer predisposition genes are frequent among patients with locally advanced or metastatic urothelial carcinoma, but their prevalence and significance in patients with non-muscle-invasive bladder cancer (NMIBC), the most common form of urothelial carcinoma, is understudied. Germline analysis was conducted on paired tumor/normal sequencing results from two distinct cohorts of patients initially diagnosed with NMIBC. Associations between clinicopathologic features and clinical outcomes with the presence of P/LP germline variants in ≥76 hereditary cancer predisposition genes were analyzed. A similar frequency of P/LP germline variants were seen in our two NMIBC cohorts [12% (12/99) vs. 8.7% (10/115), P = 0.4]. In the combined analysis, P/LP germline variants were found only in patients with high-grade NMIBC (22/163), but none of the 46 patients with low-grade NMIBC (13.5% vs. 0%, P = 0.005). Fifteen (9.2%) patients with high-grade NMIBC had P/LP variants in DNA damage response genes, most within the nucleotide excision repair (ERCC2/3) and homologous recombination repair (BRCA1, NBN, RAD50) pathways. Contrary to prior reports in patients with NMIBC not receiving Bacillus Calmette-Guerin (BCG), P/LP germline variants were not associated with worse recurrence-free or progression-free survival in patients treated with BCG or with risk of developing upper tract urothelial carcinoma. Our results support offering germline counseling and testing for all patients with high-grade bladder cancer, regardless of initial tumor stage. Therapeutic strategies that target impaired DNA repair may benefit patients with high-grade NMIBC.
Identifiants
pubmed: 35833951
pii: 707011
doi: 10.1158/1078-0432.CCR-22-1006
pmc: PMC9527498
doi:
Substances chimiques
Adjuvants, Immunologic
0
BCG Vaccine
0
Xeroderma Pigmentosum Group D Protein
EC 3.6.4.12
ERCC2 protein, human
EC 5.99.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4267-4277Subventions
Organisme : NIH HHS
ID : UL1 TR002384
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA221745
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002384
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA082088
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA184746
Pays : United States
Informations de copyright
©2022 The Authors; Published by the American Association for Cancer Research.
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