Germline BRCA1/BRCA2 mutations among high risk breast cancer patients in Jordan

Abstract

BackgroundBreast cancer is the most common malignancy and the leading cause of cancer-related deaths among Jordanian women. With a median age of 50 years at diagnosis, a higher prevalence of hereditary breast cancer may be expected. The objective of this pilot study is to evaluate, for the first time, the contribution of germline mutations in BRCA1/2 to breast cancer among Jordanian patients.MethodsJordanian breast cancer women with a selected high risk profile were invited to participate. Peripheral blood samples were obtained for DNA extraction. A detailed 3-generation family history was also collected. BRCA sequencing was performed at a reference laboratory. Mutations were classified as deleterious, suspected deleterious, variant of uncertain significance or favor polymorphisms. Patients’ medical records were reviewed for extraction of clinical and tumor pathology data.ResultsOne hundred patients were enrolled to the study. Median age was 40 (22–75) years. In total, 20 patients had deleterious and 7 suspected deleterious mutations in BRCA1 or BRCA2 genes. Seven variants of uncertain significance were also detected. After excluding patients tested subsequent to the index case in their families, highest mutation rates were observed among triple negatives (9/16, 56.3%) especially among those with positive family history of breast and/or ovarian cancer (9/13, 69.2%), patients with bilateral or second primary breast cancer (10/15, 66.7%) and those with family history of male breast cancer (2/5, 40.0%).ConclusionsBRCA1/2 mutations are not uncommon among selected Jordanian females with breast cancer. The contribution of these findings to much younger age at diagnosis is debatable.Although small, our selected patient cohort shows an important incidence of deleterious and suspected deleterious BRCA1/2 mutations suggesting that genetic testing should be offered to patients with certain high risk features.

Patterns and Prevalence of Germline BRCA1 and BRCA2 Mutations among High-Risk Breast Cancer Patients in Jordan: A Study of 500 Patients

“…The fact that breast cancer is diagnosed at a younger age in our region can be a factor. We are in the process of combining the cohort of younger patients included in this study and our previous one [ 19 ] to study the contribution of age, in the absence of other risk factors, to the risk of carrying BRCA1 or BRCA2 mutation.…”

“…In total, 20 (20.0%) patients had deleterious (pathogenic) and 7 (7.0%) others had suspected deleterious (likely pathogenic) mutations in BRCA1 or BRCA2 genes. Highest mutation rates were observed among patients with triple-negative disease (negative for estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor (HER2) receptors), especially among those with a positive family history of breast and/or ovarian cancer, patients with bilateral or second primary breast cancer, and those with a family history of male breast cancer [19].…”

Contribution of BRCA1 and BRCA2 germline mutations to early onset breast cancer: a series from north of Morocco

“…Studies among unselected EOBC (< 40 years) from Middle East and North Africa (MENA) region showed disparate results with a BRCA mutation rate ranging from 0 to 26% [12][13][14][15] (Table 3). Fortunately, all these reports have sequenced both BRCA genes and also analyzed large genomic rearrangements, unlike our work.…”

Global celebrities' effect on health awareness among Jordanians: A study using the case of Angelina Jolie

“…The primary focus of the scarcely available service is mostly birth defects, metabolic inborn errors, and hemoglobinopathies. Recently, KHCC has established a cancer‐focused genetic counseling service because of the perceived need of the patients (Abdel‐Razeq et al, ), their families, and the community in general. This service is directed toward breast cancer patients, the largest cancer patient population at KHCC, to set a model for cancer‐related genetic counseling.…”

“…Clinical cancer genetic testing for BRCA1/2 mutations has been available in the West since 1996 (Edlich, Winters, & Lin, ), but is yet to be widely accessible in Middle‐Eastern countries and locally in Jordan (Abdel‐Razeq, Al‐Omari, Zahran, & Arun, ). This does not mean that genetic testing knowledge and practices are completely absent from the Arab world.…”