Inherited Germline Cancer Susceptibility Gene Variants in Individuals with Non-Muscle-Invasive Bladder Cancer.

Autor:	Pietzak EJ; Urologic Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Whiting K; Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York., Srinivasan P; Marie-Josée & Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York., Bandlamudi C; Marie-Josée & Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York., Khurram A; Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Joseph V; Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Walasek A; Urologic Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Bochner E; Urologic Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Clinton T; Urologic Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Almassi N; Urologic Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Truong H; Urologic Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., de Jesus Escano MR; Urologic Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Wiseman M; Urologic Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Mandelker D; Diagnostic Molecular Pathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York., Kemel Y; Niehaus Center for Inherited Cancer Genomics, Memorial Sloan Kettering Cancer Center, New York, New York., Zhang L; Diagnostic Molecular Pathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York., Walsh MF; Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Cadoo KA; Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; St. James's Hospital Dublin, Trinity College Dublin, Trinity St. James's Cancer Institute, Dublin, Ireland., Coleman JA; Urologic Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Al-Ahmadie H; Genitourinary Pathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York., Rosenberg JE; Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Iyer GV; Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Solit DB; Marie-Josée & Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.; Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York., Ostrovnaya I; Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York., Offit K; Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Robson ME; Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Stadler ZK; Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Berger MF; Marie-Josée & Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.; Diagnostic Molecular Pathology Service, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York., Bajorin DF; Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Carlo M; Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Bochner BH; Urologic Oncology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2022 Oct 03; Vol. 28 (19), pp. 4267-4277.
DOI:	10.1158/1078-0432.CCR-22-1006
Abstrakt:	Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: 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. (©2022 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu