Prevalence of pathogenic germline cancer risk variants in high-risk urothelial carcinoma.

ABSTRACT: PURPOSE:To date, there has not been a large, systematic evaluation of the prevalence of germline risk variants in urothelial carcinoma (UC). METHODS:We evaluated the frequency of germline pathogenic and likely pathogenic variants in 1038 patients with high-risk UC who underwent targeted clinical germline testing. Case-control enrichment analysis was performed to screen for pathogenic variant enrichment in 17 DNA repair genes in 1038 UC patients relative to cancer-free individuals. RESULTS:Among 1038 patients with UC, the cumulative frequency of patients with pathogenic variants was 24%; 18.6% of patients harbored ?1 actionable germline variant with preventive or therapeutic utility. MSH2 (34/969, 3.5%) and BRCA1/2 (38/867, 4.4%) germline variants had the highest frequency. Germline variants in DNA damage repair genes accounted for 78% of pathogenic germline variants. Compared to the cancer-free cohort, UC patients had significant variant enrichment in MSH2 (odds ratio [OR]: 15.4, 95% confidence interval [CI]: 7.1-32.7, p?

SUBMITTER: Nassar AH 

PROVIDER: S-EPMC7118025 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature