A case-control study of BRCA1 founder mutations 185delAG and 5382insC in a cohort of Egyptian ovarian cancer patients using pyrosequencing technique

• Published in: Egyptian Journal of Medical Human Genetics 2022-01, Vol.23 (1), p.11-9
• Main Authors: Rizk, Mohamed M, El-etreby, Nour M, El-Attar, Lama M, Elzyat, Eman A, Saied, Marwa H
• Format: Article
• Language: English
• Subjects: Analysis; BRCA1 gene; BRCA1 protein; BRCA2 gene; BRCA2 protein; Breast cancer; Cancer; Cancer patients; Care and treatment; Chemotherapy; Development and progression; Familial ovarian cancer; Family medical history; Founder mutation; Gene mutations; Genetic aspects; Genetic screening; Metastases; Methods; Mutation; Oncology, Experimental; Ovarian cancer; Patients; Peripheral blood; Pyrosequencing; Tumors
• ISSN: 1110-8630; 2090-2441
• DOI: 10.1186/s43042-022-00226-8

Background Ovarian cancer (OC) is considered a leading cause of death among women with gynecological malignancies. OC, like breast cancer, shows a familial predisposition to germline mutations in genes BRCA1 or BRCA2, which have proved to play important roles in the incidence and progression of cancers. In Arab countries there are limited data concerning BRCA1 or BRCA2 founder mutations associated with familial ovarian cancer (FOC). Therefore, the aim of this pilot study was to assess two common founder mutations of BRCA1 (185delAG and 5382insC) in a cohort of Egyptian patients with FOC. The study included fifty female patients with FOC and twenty healthy controls. Clinical, laboratory, and pathological findings were assessed as well as response to therapy. Genetic testing for BRCA1 (185delAG and 5382insC) mutations was performed on peripheral blood samples using a short-fragment sequencer (pyrosequencer). Results The BRCA1 185delAG mutation was not observed in either the FOC patients or the controls. However, the carrier frequency of heterozygous BRCA1 5382insC mutation was 8%. All the FOC patients with a BRCA1 5382insC mutation had a positive family history of cancer (p = 0.009). All carriers of the BRCA1 5382insC mutation showed a preliminary good response to chemotherapy. The majority of carrier patients were diagnosed at an advanced stage of the disease with high-grade tumors and distant metastasis (75% of cases). Conclusion The frequency of the BRCA1 5382insC mutation in FOC patients was 8%. The strong association between the mutation and the positive family history suggests that a wider screening for BRCA1 founder mutations would be valuable in predicting high-risk individuals.