Breast cancer in West Africa: molecular analysis of BRCA genes in early-onset breast cancer patients in Burkina Faso

Abstract

Background Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths among women in Africa after cervical cancer. Even if the epidemiological data are now aligned with those relating to industrialized countries, the knowledge concerning breast cancer in Africa, particularly in Western Africa, still lack clinical data, medical treatments, and the evaluation of genetic and non-genetic factors implicated in the etiology of the disease. The early onset and the aggressiveness of diagnosed breast cancers in patients of African ancestry strongly suggest that the genetic risk factor may be a key component, but so far, very few studies on the impact of germ line mutations in breast cancer in Africa have been conducted, with negative consequences on prevention, awareness and patient management. Through Next Generation sequencing (NGS), we analyzed all of the coding regions and the exon–intron junctions of BRCA1 and BRCA2 genes—the two most important genes in hereditary breast cancer—in fifty-one women from Burkina Faso with early onset of breast cancer with or without a family history. Results We identified six different pathogenic mutations (three in BRCA1, three in BRCA2), two of which were recurrent in eight unrelated women. Furthermore, we identified, in four other patients, two variants of uncertain clinical significance (VUS) and two variants never previously described in literature, although one of them is present in the dbSNP database. Conclusions This is the first study in which the entire coding sequence of BRCA genes has been analyzed through Next Generation Sequencing in Burkinabe young women with breast cancer. Our data support the importance of genetic risk factors in the etiology of breast cancer in this population and suggest the necessity to improve the genetic cancer risk assessment. Furthermore, the identification of the most frequent mutations of BRCA1 and BRCA2 in the population of Burkina Faso will allow the development of an inexpensive genetic test for the identification of subjects at high genetic cancer risk, which could be used to design personalized therapeutic protocols.

Screening of BRCA1/2 variants in Mauritanian breast cancer patients

“…The relatively high and concordant frequency in our cohort and in Senegal further highlights the pathogenic character of this variant in BC assessment and prevention in West African families [27,[31][32][33].…”

Combining Organoid Models with Next-Generation Sequencing to Reveal Tumor Heterogeneity and Predict Therapeutic Response in Breast Cancer

“…Given that targeted therapy must be based on identifying dominant drivers of oncogenesis, NGS should be a powerful implement for clinical decision-making and the development of biological agents [32]. For example, the application of NGS to studies of BRCA mutations in population-based cohorts has contributed to the update of clinical recommendations for disease screening and medication intervention, such as PARPi [33][34][35]. Despite the promising guiding significance of NGS, one problem is that NGS-detected alterations in gene signatures rely on the functional annotation to elucidate subsequent biological changes.…”

Uncovering Evidence: Associations between Environmental Contaminants and Disparities in Women’s Health

“…It is well known that genetic variations also contribute to an individual woman's risk of developing breast cancer. Women with BRCA1/2 mutations are at increased risk of breast cancer and are known to contribute to the familial occurrence of this disease in most, if not all, ethnicities [73,74]. Beverly et al reported that white women with breast cancer exhibited a higher prevalence of estrogen and progesterone receptors compared to Black women with breast cancer-which may contribute to improved survival rates in white women since many breast cancer treatments target hormone receptors [75].…”