Introduction
Breast cancer continues to be one of the leading causes of cancer-related mortality among women globally, with hereditary factors playing a significant role in a subset of these cases. Pathogenic variants within the BRCA1 and BRCA2 genes are known to markedly increase the risk for developing breast and ovarian cancers. While extensive research has been conducted in various populations to identify such mutations, there has been limited information available regarding hereditary breast cancer within sub-Saharan African populations, particularly in Senegal.
A recent study, published in BMC Medical Genetics, has identified a novel nonsense pathogenic BRCA2 variant in a consanguineous Senegalese family with a history of hereditary breast cancer, shedding light on the genetic susceptibility to breast cancer in African populations and emphasizing the importance of inclusive genetic screening.
Discovery of BRCA2 Pathogenic Variant in Senegalese Family
In a groundbreaking discovery, a team of researchers led by Dr. Diop Jean Pascal Demba from the Laboratory of Cytology, Cytogenetics and Reproductive Biology at Le Dantec Hospital in Dakar, Senegal, identified a novel BRCA2 variant in a consanguineous family affected by hereditary breast cancer. The study included an index case from this family and nineteen healthy female relatives, alongside controls consisting of 48 healthy women without a cancer diagnosis and 48 women diagnosed with sporadic breast cancer without a family history.
The research team extracted genomic DNA from peripheral blood and amplified all BRCA2 exons through polymerase chain reaction (PCR), followed by sequencing. By comparing the sequences to the BRCA2 GenBank reference using Alamut Software, they found a previously unreported nonsense variant, c.5219 T > G; p.(Leu1740Ter), located in exon 11 of the BRCA2 gene in the index case. The study documented this pathogenic variant in three sisters and one daughter, but not in the unaffected control group or unrelated cases, signifying its likely contribution to cancer predisposition in the family.
This finding, reported in the BMC Medical Genetics journal with DOI: 10.1186/s12881-019-0814-y, represents the first recorded novel BRCA2 pathogenic variant in this population. The identification of such a mutation not only contributes to the understanding of genetic diversity in cancer susceptibility across different populations but also emphasizes the need for a more comprehensive approach to genetic screening that includes underrepresented groups.
Epidemiology of BRCA Mutations and Breast Cancer
The profound impact of BRCA mutations on breast cancer incidence has been well-documented. Historically, research and genetic testing have focused primarily on populations of European descent, leaving a gap in knowledge concerning the prevalence and spectrum of BRCA mutations in African countries. The GLOBOCAN 2012 report highlighted the global burden of cancer and emphasized the need for more inclusive research (Ferlay et al., Int J Cancer, 2015).
As incidence rates of breast cancer continue to rise globally, including in sub-Saharan Africa, understanding the role of BRCA mutations in these populations becomes increasingly critical. The novel pathogenic BRCA2 variant identified in the Senegalese family contributes to the growing body of evidence that there is considerable genetic heterogeneity within and between populations. Such findings challenge the adequacy of current genetic testing protocols that may not consider this diversity (Fackenthal et al., J Med Genet, 2005).
Implications for Genetic Screening and Counseling
The discovery of the BRCA2 pathogenic variant unique to the Senegalese population has significant implications for genetic counseling and testing strategies. With the knowledge that hereditary breast cancer can be influenced by specific BRCA mutations within certain ethnic groups, genetic screening programs must adapt to address these distinct genetic risk factors.
The adoption of more inclusive screening protocols that account for the identified variant could enable earlier detection, targeted interventions, and potentially improved survival rates for at-risk individuals within this population. Moreover, the identification of this mutation has a potential impact on family members who may also carry the variant and be at an increased risk of developing breast cancer.
Challenges and Future Research
While the study marks a significant step toward understanding the genetic basis of breast cancer in the Senegalese population, challenges remain. One of the major hurdles is the accessibility and affordability of genetic testing, particularly in resource-limited settings. Moving forward, it is crucial that future research endeavors aim to address these barriers to ensure equitable access to genetic services.
Furthermore, expanding the scope of research to include larger sample sizes and other sub-Saharan African populations will likely uncover additional pathogenic variants unique to these groups, thereby enriching the global genomic database. This will also facilitate the development of precise risk assessment models and tailored prevention strategies.
Conclusion
The identification of the novel BRCA2 pathogenic variant in a Senegalese family highlights the necessity of including diverse populations in genetic research. This study underscores the importance of equitable genetic screening and the potential benefits of its findings in the clinical setting, where such information can guide tailored prevention and management strategies for hereditary breast cancer.
For a broader reach and effective public health interventions, concerted efforts from clinicians, genetic counselors, and policymakers are required. As we advance into an era prioritizing precision medicine, the diversity of genetic makeup in different populations cannot be overlooked.
References
1. Diop Jean Pascal Demba et al. (2019). Novel BRCA2 pathogenic variant c.5219 T > G; p.(Leu1740Ter) in a consanguineous Senegalese family with hereditary breast cancer. BMC Med Genet. DOI: 10.1186/s12881-019-0814-y.
2. Ferlay J, et al. (2015). Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. DOI: 10.1002/ijc.29210.
3. Fackenthal JD, et al. (2005). Complete allelic analysis of BRCA1 and BRCA2 variants in young Nigerian breast cancer patients. J Med Genet. DOI: 10.1136/jmg.2004.022111.
4. Stuart J, Schnitt SRL. (2014). IARC Library Cataloguing in Publication Data. World Cancer Report.
5. Golubnitschaja O, et al. (2016). Breast cancer epidemic in the early twenty-first century: evaluation of risk factors, cumulative questionnaires and recommendations for preventive measures. Tumour Biol. DOI: 10.1007/s13277-016-5095-9.
Keywords
1. BRCA2 gene variant breast cancer
2. Hereditary breast cancer Senegal
3. Genetic screening sub-Saharan Africa
4. Pathogenic BRCA mutation detection
5. Consanguineous family cancer genetics