Study of the Incidence of BRCA1/2 Mutation in Egyptian Female Breast Cancer Patients and Its Impact on Clinical Outcome

Abstract

Breast cancer affects more than 1.7 million women worldwide each year and accounts for about 14% of cancer-related deaths. The overall worldwide burden of breast cancer showed 20% increase in incidence and 14% increase in mortality in the previous five years, with increasing rates occurring predominantly in developing countries, including Egypt. Despite much research directed at understanding and controlling breast cancer, it is the most common cancer among women in Egypt and persists as a major public health problem. The lack of public awareness and the financial shortages that impede genetic screening and diagnostic services render chances of survival low and mortality rates correspondingly high. Germline mutations of the breast-cancer susceptibility gene 1 (BRCA1) and breast-cancer susceptibility gene 2 (BRCA2) are the strongest genetic predictors of breast cancer. Ethnic variations in breast cancer epidemiology and genetics worldwide have necessitated investigation of the spectrum of BRCA1 and BRCA2 mutations in different populations. Knowledge about the presence of founder mutations in Egypt will enable the development of novel prevention strategies and may impact on treatment. This study was undertaken to investigate the frequency and profile of BRCA1 and BRCA2 mutations in Egyptian female breast cancer patients. Furthermore, we aimed to assess the association of BRCA mutation status Summary and Conclu sion 137 with clinicopathological features and determine its impact on clinical outcome. The study cohort comprised 103 Egyptian female breast cancer patients unselected for age of onset of breast cancer or family history or any criterion that would enrich for BRCA1/2 mutations. All enrolled patients were diagnosed with primary invasive breast cancer and have undergone surgery with curative intent before 2008. For all recruited patients, detailed personal history was collected; clinical and pathological data, and course of the disease were extracted from the hospital medical records. Blood samples were collected from all participants followed by DNA extraction. Mutational screening of some exons of BRCA1 and BRCA2 genes was performed using high-resolution melting (HRM) analysis followed by direct sequencing of detected variants. The DNA sequences were analyzed by visual examination of the chromatogram followed by sequence alignment using the respective tools. To assess whether the spectrum of mutations identified in our Egyptian cohort is similar to those found in other populations, we checked the mutations identified in this study for reports in several BRCA mutational databases. Potential clinical effects of the detected UVs on protein structure and function were evaluated using In Silico prediction tools. In addition to this, we examined the association of BRCA mutation status, whether deleterious mutations or UVs, with the clinical and pathological characteristics of the studied cases. We further explored whether disease free survival (DFS) differs in BRCA mutation carriers and