Prevalence and clinical implications of germline mutations among Jordanian patients with ovarian cancer. The Jordanian exploratory cancer genetics (Jo-ECAG) ovarian study

Mol Genet Genomic Med. 2022 Dec 19;e2125. doi: 10.1002/mgg3.2125. Online ahead of print.


Background: Ovarian cancer is one of the most common gynecological malignancies. Due to the absence of effective screening methods, ovarian cancer is usually diagnosed at late stages. Patients with pathogenic and likely-pathogenic germline variants (PGVs) in BRCA1 or BRCA2 harbor elevated risk of developing both ovarian and breast cancers. Identifying PGVs may help in both cancer prevention and active disease treatment. Worldwide prevalence of PGVs varies and the matter is poorly addressed among Arab patients.

Methods: Patients with epithelial ovarian, fallopian tube or primary peritoneal cancers were offered the universal 20 or 84-multi-gene panel testing as per standard guidelines. Cascade family screening was also offered to all first and second-degree relatives of PGV positive patients. Genetic testing was done at a referral lab using a next generation sequencing (NGS)-based platform.

Results: During the study period, 152 patients, median age (range): 50 (18-79) years old, were tested. The majority (n = 100, 65.8%) had high-grade serous carcinoma, and 106 patients (69.7%) had metastatic disease at presentation. In total, 38 (25.0%) had PGVs, while 47 (30.9%) others had variants of uncertain significance (VUS). PGVs were mostly in BRCA1 (n = 21, 13.8%) and in BRCA2 (n = 12, 7.9%), while 6 (3.9%) others had PGVs in non-BRCA1/2 genes. PGV rates were significantly higher among 15 patients with a positive family history of ovarian cancer (60.0%, p = .022) and among 52 patients with a positive family history of breast cancer (40.4%, p = .017).

Conclusions: PGVs are common among Jordanian women with ovarian cancer, and mostly occur in BRCA1/2. Given its clinical impact on disease prevention and precision therapy, universal testing should be routinely offered.

Keywords: BRCA1; BRCA2; PARP inhibitors; ovarian cancer; pathogenic germline variant.