Testing for Breast Cancer

Genetic testing is a powerful new way to find out about your risks for certain diseases. One example is the test for one of the “Breast Cancer” genes, for example BRCA1. (BRCA stands for BReast CAncer.)
Before we dive into a discussion of BRCA1, let’s review a little terminology. Perhaps you’ve heard that a person is “made” from their genes. This is true — what makes the human species different from other mammals is the sequences of DNA in our cells. Our genes also play a large role in determining who we are, although genes aren’t everything: Identical twins have the same genes but are still different people. Genes are actually nothing more than sequences of DNA which contain the instructions for building a small molecular machine called a protein. Just like blueprints at a factory, there are different versions of these instructions (as in the “Revision A” and “Revision B” iMacs). These different versions of genes are called “alleles”. Sometimes you’ll hear an allele referred to as a “mutation” or that it is “malformed”. Indeed, often times it is quite clear that the gene is broken (just like a blank blueprint would clearly be broken). Other times it isn’t so clear what the “mutation” does — and in fact it is possible that a mutation would function better than the original (otherwise known as the “wild type”). For example, there may be alleles that make you short (a loss or reduction of function of the human growth hormone) or there may be alleles that make your hair dark (a gain of function in pigmentation synthesis). But no, it is not possible that a single mutation would give you strange super powers or enable you to grow feathers and fly.
A sad fact about mutations is that they are the cause of cancer. Not all mutations cause cancer, but cancer won’t happen without them. Fortunately, cells in your body are full of protection mechanisms to prevent cancer. Mutations can happen at random (due to solar radiation, chemical exposure, time or just bad luck) to any cell in your body. Most of the time a cell’s protection mechanism will either fix the mutation, or cause a cell with a cancerous mutation to die. But once in a while a cell (or the cells that it came from) gets a mutation in the protection mechanism itself. Once a cell’s protection mechanism is disabled, the cell can accumulate more mutations that eventually allow it to become cancerous.
One kind of cellular protection mechanism is called a “tumor suppressor gene”.
Okay, back to BRCA1. What is it, and why does it cause breast cancer? It appears from the literature (a summary can be found at NIH ) that BRCA1 is a tumor suppressor gene. The protein made from the BRCA1 gene acts to suppress cancer! BRCA1 can be dangerous to your health only if it is mutated. The protein made from the mutated gene may be partially or completely broken, leaving your cells more susceptible to becoming cancerous. And remember, your cells can become mutated two ways: Either you inherited that mutation from your parents, or you acquired it.
As researchers have studied BRCA1, they’ve discovered that it is similar to other tumor suppressor genes that have already been studied. In fact, BRCA1 normally protects you from not only breast cancer but also ovarian and prostate cancers. It’s also been discovered that BRCA1 mutations are associated with certain groups of people, for example the Ashkanazi Jews. It appears that over 2% of the Ashkanazi may have a mutation in BRCA1. Indeed the unusually high incidence of breast cancer in a region of New Jersey can largely be attributed to the high number of Ashkanazi descendents living in that area.
BRCA1 is not the answer to all of the Ashkanazi problems, however — it has been shown that even the Ashkanazi who have normal BRCA1 are still three times more likely than other people to develop breast cancer. This just goes to show that cancer is a complex subject and the genetics of this disease are still being figured out.
An example family pedigree.
Let’s look at the example family pedigree above. One woman (marked with an X) is facing a breast cancer triple threat: She’s already had breast cancer, which means she is more likely to get it again than most people. Plus her grandmother was an Ashkanazi Jew. Grandma may have had a mutation in BRCA1; even if she didn’t the Ashkanazi have a higher incidence of breast cancer than most people. X wonders if it would be worthwhile having her BRCA1 and BRCA2 genes sequenced. This is an expensive but painless procedure. It is expensive because the BRCA genes are long, and the entire DNA sequence needs to be verified in order to know if there is a mutation present.
The issue is complicated because it raises questions that don’t affect just her. She has living cousins, some of whom have already had cancer. If X has mutant BRCA1, cousin Y has a 25% chance that she also has that mutation. Should she tell her the results of her genetic screening? There is no simple answer to that question.
Since BRCA1 is also indicated in male breast cancer as well as prostate cancer, should she tell her four sons the results? Each son has a 50% chance of inheriting the mutation — so there is over 90% chance that at least one of them did. What about her granddaughter? Again, there are no easy answers here.
In my opinion, the more information you have, the better. Chances are, X does not have a mutation in BRCA1. Confirming that with sequencing would provide comfort to the whole family. On the small chance that she does have a mutation, that knowledge provides the opportunity to consider more aggressive treatments to prevent future cancer. It also forewarns her relatives to be more vigilant. So her son’s don’t disregard any lumps, or may have their genes sequenced themselves and will seek routine screening for cancer.
Genetic screening is the latest in diagnostic tools that will help us live healthier lives. While intially it is a bit intimidating, once the legal and technical aspects of it are worked out it will become as routine as getting a culture for strep throat or being vaccinated.