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Your Say: Tackling The Brcai Mutation

By JASON CAREY PhD

Breast cancer researcher

The University of Texas

THE islands of the Bahamas are known for their beautiful beaches and pristine clear waters, a marvel many across the globe seek out in their travels.

The Bahamas, like the rest of the Caribbean, became the epicentre of a global economical transition, fuelled by an undiscovered continent and the promise of untold wealth.

This cultural explosion was fuelled on the backs of African slaves immigrated to the New World as a cornerstone to the global expansion of the European settlers. To this day, that great migration is evident in the genetic makeup of the Bahamian people and serves as the basis for the reason why women in the Bahamas have the greatest worldwide risk of hereditary breast cancer.

The BRCA1 and BRCA2 genes were first discovered in 1990 and have since been linked to a genetic predisposition to breast and ovarian cancer in women. Several other studies have linked BRCA genetic mutations to other types of cancer including pancreatic and prostate.

Research studies have drawn a significant correlation between individuals with BRCA mutations and incidences of breast/ovarian cancer. The greater than 75 per cent lifetime risk signifies that women with a BRCA1/2 mutation are very likely to develop either breast or ovarian cancer within the course of their lifetimes.

This genetic mutation is one of the greatest predictors of cancer among the human race. The good news is that the frequency of BRCA1 mutations is less than 1 per cent in the general population.

Specific ethnic groups, however, have been shown to have a higher association of BRCA1 mutations, specifically the Ashkenazi Jewish population.

This term refers to Jewish people of eastern European descent. In the late 1990s, studies estimated that the overall frequency of BRCA1/2 mutation within the Ashkenazi Jewish population is approximately 2.65%. Of Ashkenazi Jewish women who develop breast/ovarian cancer, approximately 11 per cent were estimated to arise as a result of mutations within the BRCA1/2 gene.

These findings about the association of Ashkenazi Jews and breast cancer risk have initiated a flurry of studies about population-based risk for breast/ovarian cancer via BRCA1/2. As a result, the genetics of the Ashkenazi Jewish population have been extensively studied in an attempt to understand how BRCA1 hereditary breast cancer arises. The most frequent mutation of the Ashkenazi Jewish population is 185delAG. This mutation results in an alteration of the gene expression, impairing its functions and resulting in the induction of cancer. Until recently, this population of women has embodied the association of BRCA1/2 hereditary breast cancer risk. Thus, the medical community has invested heavily in understanding the significance of their risk.

In 2011, it was discovered that women in the Bahamas have a much higher association of breast cancer risk than even the Ashkenazi Jewish population.

Qualitative observation of Bahamian women developing breast cancer at very young ages – less than 40 years old – lead to an initial study investigating the frequency of BRCA1/2 mutations in Bahamian women who had developed breast or ovarian cancer.

This lead to the conclusion that of the women who had developed cancer, 23 per cent were due to BRCA1/2 mutations. As whole population studies are currently underway (Bahamas Breast Cancer Initiative Foundation), the overall frequency of BRCA1 mutation within the general population in the Bahamas is yet to be determined. Estimates suggest that the frequency of this mutation may be as high as 4% within the general Bahamian population. Several types of BRCA1 mutations were observed in the Bahamian population, but greater that 90 per cent of the associated BRCA hereditary breast cancer was one specific mutation: IVS13+1G>A, an African founder mutation. The Bahamas is a population with greater than 90 per cent of African descent, therefore a founder mutation previously associated with individuals of African descent is not surprising and reflects the essence of the African heritage reflected in the DNA of Bahamian people.

Even more interesting is that this mutation has not been associated with Ashkenazi Jewish women, indicating a totally different inherent risk association.

So what does this mean? Will there be a rush to study Bahamian women, or even women in the Caribbean of African descent to determine the impact of these mutations on the general population?

In short, where exactly the future of BRCA1 hereditary breast cancer research in the Bahamas will lead, no one knows. Initial studies are currently underway and hopefully will yield some answers. The Bahamas, however, is not an island with vast medical resources for research and the world seems content with what they think they know about the associated risk of breast cancer via BRCA1. It is clear that these observations need to be studied further.

Although we know that BRCA1 mutations indicate a higher risk, there is still a whole lot we do not yet know. Specifically, what can trigger the onset of breast cancer in individuals with this inherited risk? Although we know that individuals with known BRCA1 mutations will likely develop breast or ovarian cancer, we have yet to determine how to prevent the onset of this disease in those individuals aside from a mastectomy or oophorectomy.

On the reverse side, there are hundreds of types of BRCA1 mutations, and several of these mutations have not been linked to any cancer, thus yielding no answers on the appropriate approach in individuals with these inconclusive mutations.

Research is key to tapping into the code in our DNA. Although BRCA is seen as the Holy Grail for understanding breast/ovarian cancer risk, there are several other known genes that pose association with cancer but are ignored due to the low mutation frequency. What do we do about those?

The solution may not be simple but it begins with a complete understanding of who we are as a people, genetically speaking, and what genetic testing can tell us about our risk.

For more information on hereditary breast cancer in the Bahamas go to www.bbcif.com.

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