Earlier this year, Angelina Jolie shocked the world when she
revealed that she had undergone surgery to remove both her breast
and have reconstructive surgery because of a positive BRCA test. In June the US Supreme
Court ruled it was illegal to patent a gene as a direct result of the BRCA test
debacle. Over the past year a lot of fuss has been made about the term BRCA
test, but exactly what does it mean? The media in general can be a bit
misleading when equating a BRCA test to the equivalent of other diagnostic test
such as HIV or tuberculosis tests. A positive BRCA test does not mean you have
cancer, neither does it mean you have contracted a foreign disease, known as
BRCA. Truth be told, BRCA is an essential part of all of us, man woman and
child, and plays a very important role in all of our bodies not only in the
fight against cancer but as a function of the body’s ability to repair DNA
damage.
Believe it or not, we live in a world that is constantly
causing us harm. However, the human body is magnificently resilient and repairs
this constant damage inflicted upon us every day of our lives. Just like the
body is able to repair a wound when you are cut, so can the body repair the
microscopic damage caused daily by our environment. One of the most common
examples of daily DNA damage is as a result of UV radiation, the sun. As the
harmful UV rays destroy our skin, it can mutate the cells within our skin
causing repairable harm. Two of the genes responsible for repairing this damage
are BRCA1 & BRCA2. These genes play a crucial role in finding and repairing
damaged DNA within our bodies, in order to prevent the cells in our body from
multiplying with this DNA damage in tact, leading to catastrophic chaos.
Although these genes play a crucial role in repairing DNA
damage throughout the body, it was discovered early on that mutations within these
genes are frequently found in women with breast and ovarian cancer at a young
age. These common mutations that have been discovered in cancer patients,
founder mutations, prevent these genes from binding to DNA in order to repair
damage being caused in the body. Although these interactions are occurring at a
microscopic level they have a significant effect on the entire human body.
Exactly why mutations within BRCA1 & BRCA2 lead to breast and ovarian
cancer more than any other cancer, is still somewhat a mystery to science.
However, these mutations are inherited from parent to progeny and can also
cause other types of cancer including prostate, stomach, pancreatic and colon
cancer.
What exactly is a BRCA test? With the advancement in
technology, science is readily able to detect whether individuals have
mutations within these genes that disable their function. With the initial
discovery of these genes, science has spent a considerable amount of time
deciphering what these mutations mean, and as a result they have estimated that
women with mutations within the BRCA1 & BRCA2 genes have a greater than 50% (50-85%) lifetime risk of developing breast or ovarian cancer. That is significantly
higher than the overall risk of the general population, which stands at approximately
10%. A BRCA test detects these specific mutations
within women, and estimates the relative risk of developing cancer based upon
the frequency of specific mutations in previous cancer patients. And as these
mutations are passed down from generation to generation they often coincide
with a history of cancer within a family.
The primary reason Angelina Jolie decided to undergo double
mastectomy, removal of both her breasts, was not only because she tested
positive for a BRCA mutation but because she also had a history of breast
cancer within her family, significantly increasing her individual risk.
Additionally, by undergoing radical double mastectomy she cuts her risk of
developing breast cancer by 90%. Having her ovaries removed would further reduce her risk
of developing ovarian cancer. However, these surgical intervention strategies
possess life-altering risks and should be discussed under direct advisement of
a primary physician.
One final caveat; the world has developed a heightened sense
of the significance of BRCA positivity. However, in reality we still do not
know everything there is to know about the genes BRCA1 & 2. There are over
500 different types of documented mutations in BRCA1 and over 300 documented
mutations in BRCA2. Only small subsets of these mutations have been correlated
with causing cancer, we call those founder mutations. These mutations usually
congregate in specific demographic populations, with Ashkenazi Jewish women
and Bahamian women being two populations with the highest frequency of BRCA
mutations.
Photo credit: NCI (Over 500 different types of BRCA1 mutations) |
Debated as either the curse of knowing or a preventative
cure, BRCA testing has developed as our most advanced weapon in the fight to
prevent breast & ovarian cancer. In families of women stricken by this
disease, BRCA testing has offered the first defense in ending this curse. As
the discovery of these genes is less than 25 years old, our understanding on
their impact on society has dramatically evolved. Therefore, over the next 25 years we may develop a treatment strategy that makes BRCA mutation a negligible
overall risk for cancer.
Until then, knowing your risk is the first step to
preventing cancer.