Patterns and Frequency of Pathogenic Germline Mutations among Patients with Newly-Diagnosed Endometrial Cancer: The Jordanian Exploratory Cancer Genetics (Jo-ECAG) Endometrial Study.

Simple Summary: Endometrial cancer is a common cancer among women worldwide. In rare occasions, it can be caused by mutations in genes that can be inherited, and, mostly, as part of the Lynch syndrome that can also increase the risk of developing other cancers, mostly colorectal. In this study, we analyzed genetic alterations in 130 Arab patients with endometrial cancer. Among the whole group, 18 (13.8%) patients had positive mutations in MLH1, PMS2, MSH2, ATM, MUTYH, and BRCA2. Such mutations were more common in younger patients and in patients with specific endometrial cancers like carcinosarcoma and clear cell carcinoma. Most of endometrial cancers are sporadic, with 5% or less being attributed to inherited pathogenic germline mutations and mostly related to the Lynch syndrome. To our knowledge, this is the first study to investigate patterns and frequencies of germline mutations in patients with endometrial cancer in an Arab region. Consecutive patients with endometrial cancer (n = 130), regardless of their age and family history, were enrolled. Germline genetic testing, using an 84-gene panel, was performed on all. Almost half of the patient population (n = 64, 49.2%) was tested based on international guidelines, while the remaining patients (n = 66, 50.8%) were tested as part of an ongoing universal germline genetic testing program. Among the whole group, 18 (13.8%) patients had positive pathogenic or likely pathogenic (P/LP) germline variants. The most common variants encountered were in MLH1 (n = 4, 22.2%), PMS2 (n = 3, 16.7%), ATM, MSH2, MUTYH, and BRCA2 (n = 2, 11.1% each). In addition, three (2.3%) patients were found to have an increased risk allele of the APC gene. P/LP variants were more common among patients with carcinosarcoma and clear cell carcinoma, younger patients (age ≤ 50 years), and in patients with a non-metastatic disease. We conclude that germline genetic variants, mostly in genes related to the Lynch syndrome, are relatively common among Arab patients with endometrial cancer. [ABSTRACT FROM AUTHOR]