BRCA gene mutations: A population based review☆
Introduction
In the post human genome era, the scientific academia across the globe has witnessed a shift from studying the genetic structure and phylogenies of the population groups to accelerating research on genetic susceptibility of various complex diseases. This paradigm shift has flagged the technical evolution of genetic testing in determining disease risk. Hence, new investigative techniques are being developed targeting specifically at mapping susceptibility genes to complex diseases, thus providing genomic annotation to the complex disease. Complex diseases are multifactorial arising from the compound effects of variation at multiple interacting genes and environment that bear a significant influence on human health (Rannala, 2001).
Cancer corresponds to the category of complex diseases, exhibiting a radically high incidence in the present era (Daly and Olopade, 2015). Breast cancer (BC) is one of the most common malignancies detected across all races and ethnicities. Reaching an advanced stage in BC would render the treatment ineffective and disfiguring, directing that its early detection should be awarded high priority thus aiding effective clinical management of the disease (Miki et al., 1994). Similarly, early detection of ovarian cancer (OC) (although less frequent than BC) should also be encouraged (Miki et al., 1994).
Human population groups are extremely diverse and the genotype-phenotype interaction tends to be population/community specific (Li et al., 2010). Different mutations in a single gene may lead to a single phenotypic expression, or different phenotypes may arise out of a single genetic reason. The answers to all this lies in our genes which tend to be population specific following the rules of endogamy. Planned community-based genetic testing in BC and OC cases can prove to be beneficial as it can provide information on the type of mutation (BC & OC specific) prevalent in the community which can be used in its management. This information can further aid in screening of individuals with respect to their community specific cancer mutations. A lot of research has been done and emphasis has been laid on the association of BC and OC with numerous mutations observed in BRCA genes (Miki et al., 1994; Hall et al., 1990; Wooster et al., 1994a; Wooster et al., 1995). Unravelling the germline genetics of BRCA1 and BRCA2 gene mutations and its tendency to be population specific may provide information which could aid in diagnostics, counseling thereby reducing the overall incidence of BC and OC.
The present review highlights key features pertaining to the distribution pattern of BRCA1 and BRCA2 gene mutations and disease pertinence among various population groups across the world. The information derived from this review can aid in identifying, screening of the individuals of a population with respect to their community specific mutations pertaining to breast and ovarian cancer.
Section snippets
Role of BRCA genes in tumor formation
Many gene products function towards maintaining the physiological wellbeing of cells. In the process of replication and DNA repair, two genes BRCA1 and BRCA2 play major roles in transcription and repair of double-strand breaks via homologous recombination (Murphy, 2010; Anantha et al., 2017). They are broadly classified as tumor suppressor genes (TSGs) inherited in an autosomal dominant fashion with incomplete penetrance (Venkitaraman, 2002). BRCA1 and BRCA2 genes play important roles not only
Conclusion
Following the human genome project, attention of the genomics and genetic research has shifted from single gene disorders towards understanding the pathogenesis and etiology, and finding new ways to prevent and treat diseases having a multifactorial etiology. Using the community-based approach in genetic testing will be useful and cost-effective as it will aid in evaluating breast and ovarian cancer risk at an early stage using ethnicity-specific mutations. Furthermore, this would enable those
Acknowledgement
This work was supported by Rajiv Gandhi Centre for Biotechnology-Department of Biotechnology (RGCB-DBT).
Compliance with ethical standards
The authors declare that they have no conflict of interest.
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Recent Advances in Cancer Diagnostics and Therapy: A Nanobased Approach
2022, Recent Advances in Cancer Diagnostics and Therapy: A Nanobased Approach
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Conflict of interest: NIL.