Patterns and prevalence of pathogenic germline mutations using multi-gene panel testing in patients with ovarian cancer: The Jordanian Exploratory Cancer Genetics (Jo-ECAG) Ovarian Study.

Abstract

e17593 Background: Ovarian cancer is one of the most common gynecological malignancies. Because of the absence of effective screening methods, ovarian cancer is usually diagnosed at late stages contributing to high mortality rates. Patients with BRCA1 and BRCA2 pathogenic germline variants (PGVs) harbor elevated risk of developing both ovarian and breast cancer. Identifying PGVs may help optimize management options and improve outcomes. The worldwide prevalence of gene mutations is variable. Multiple series have demonstrated differences in PGVs according to ethnicity and geographic area. Data about prevalence of the aforementioned PGVs among Arab patients with ovarian cancer is not well understood. Methods: Patients with epithelial ovarian, fallopian tube or primary peritoneal carcinomatosis were referred for 20 or 84-multi-gene panel testing (MGPT). All patients had their diagnosis, treatment and follow up at a single cancer center. Following detailed counselling, MGPT was performed at no-cost to all patients at two reference laboratories. Descriptive statistics were performed, groups outcome was determined by two-tailed Fisher’s exact test and unpaired t-test. The study was approved by the Institutional Review Board (IRB) at King Hussein Cancer Center and all patients signed informed consent. Results: During the study period, 152 patients, median age (range): 50 (18-79) years were tested. Two patients had fallopian tube cancer, while all others had epithelial ovarian cancer. The majority (n = 100, 65.8%) had high-grade serous carcinoma, and 106 patients (69.7%) had metastatic disease on 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 only 5 (3.3%) had PGVs in non- BRCA1/2 genes ( CHECK2, MUTYH, PMS2, RAD51D, and RB1) . Age (< 50 versus ≥50) at diagnosis, histological tumor subtype, and disease stage had no impact on pathogenic variant rates. However, PGVt rates were significantly higher (60.0%, p = 0.022) among patients with positive family history of ovarian cancer and 40.4% (p = 0.017) among patients with positive family history of breast cancer. The two patients with fallopian tube cancer were both positive for BRCA1 PGVs. Only one patient underwent prophylactic bilateral mastectomies. Conclusions: PGVs in patients with ovarian cancer are common among Arabs and mostly in BRCA1/2 and rates are significantly higher among patients with family history of ovarian or breast cancers.