Prevalence of germline pathogenic BRCA1/2 variants in sequential epithelial ovarian cancer cases.
AuthorsMorgan, Robert David
Clamp, Andrew R
Mitchell, Claire L
Jayson, Gordon C
AffiliationDepartment of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
MetadataShow full item record
AbstractINTRODUCTION: Poly(ADP-ribose) polymerase inhibitors significantly improve progression-free survival in platinum-sensitive high-grade serous and endometrioid ovarian carcinoma, with greatest benefits observed in women with a pathogenic BRCA1/2 variant. Consequently, the demand for germline BRCA1/2 testing in ovarian cancer has increased substantially, leading to the screening of unselected populations of patients. We aimed to determine the prevalence of pathogenic germline BRCA1/2 variants in women diagnosed with epithelial ovarian cancer, categorised according to the established risk factors for hereditary breast and ovarian cancer syndrome and the Manchester BRCA Score, to inform risk stratification. METHODS: A cohort of sequential epithelial ovarian cancer cases recruited between June 2013 and September 2018 underwent germline BRCA1/2 testing by next-generation sequencing and multiplex ligation-dependent probe amplification. RESULTS: Five hundred and fifty-seven patients were screened. Of these, 18% had inherited a pathogenic BRCA1/2 variant. The prevalence of pathogenic BRCA1/2 variants was >10% in women diagnosed with ovarian cancer earlier than 60 years of age (21%) and those diagnosed later than 60 years of age with a family history of breast and/or ovarian cancer (17%) or a medical history of breast cancer (34%). The prevalence of pathogenic BRCA1/2 variants was also >10% in women with a Manchester BRCA Score of ?15 points (14%). DISCUSSION: Our study suggests that age at diagnosis, family history of breast and/or ovarian cancer, medical history of breast cancer or a Manchester BRCA Score of ?15 points are associated with a >10%?prevalence of germline pathogenic BRCA1/2 variants in epithelial ovarian cancer.
CitationMorgan RD, Burghel GJ, Flaum N, Bulman M, Clamp AR, Hasan J, et al. Prevalence of germline pathogenic BRCA1/2 variants in sequential epithelial ovarian cancer cases. J Med Genet. 2019 Jan 25.
JournalJournal of Medical Genetics
- Genetic screening results of individuals with high risk BRCA-related breast/ovarian cancer in Trakya region of Turkey.
- Authors: Demir S, Tozkir H, Gurkan H, Atli EI, Yalcintepe S, Atli E, Sezer YA, Eker D, Tuncbilek N, Tastekin E, Ozen Y, Cicin I
- Issue date: 2020 May-Jun
- Prevalence of BRCA1 and BRCA2 pathogenic and likely pathogenic variants in non-selected ovarian carcinoma patients in Brazil.
- Authors: Cotrim DP, Ribeiro ARG, Paixão D, de Queiroz Soares DC, Jbili R, Pandolfi NC, Cezana C, de Cássia Mauro C, Mantoan H, Bovolim G, de Brot L, Torrezan GT, Carraro DM, Baiocchi G, da Cruz Formiga MN, da Costa AABA
- Issue date: 2019 Jan 3
- Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil.
- Authors: Maistro S, Teixeira N, Encinas G, Katayama ML, Niewiadonski VD, Cabral LG, Ribeiro RM, Gaburo Junior N, de Gouvêa AC, Carraro DM, Sabino EC, Diz MD, Chammas R, de Bock GH, Folgueira MA
- Issue date: 2016 Dec 3
- High prevalence of deleterious BRCA1 and BRCA2 germline mutations in arab breast and ovarian cancer patients.
- Authors: Alhuqail AJ, Alzahrani A, Almubarak H, Al-Qadheeb S, Alghofaili L, Almoghrabi N, Alhussaini H, Park BH, Colak D, Karakas B
- Issue date: 2018 Apr
- The first Japanese nationwide multicenter study of <i>BRCA</i> mutation testing in ovarian cancer: CHARacterizing the cross-sectionaL approach to Ovarian cancer geneTic TEsting of <i>BRCA</i> (CHARLOTTE).
- Authors: Enomoto T, Aoki D, Hattori K, Jinushi M, Kigawa J, Takeshima N, Tsuda H, Watanabe Y, Yoshihara K, Sugiyama T
- Issue date: 2019 Jul