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BRCA testing for all Jews? BRCA testing for everyone?

news 2Co-written by PJGH genetic counselors Estie Rose and Chani Wiesman

This week was a very busy and exciting week for us at the Program for Jewish Genetic Health (PJGH)!  Late last week, the New York Times published two articles describing the findings and ramifications of published research conducted by renowned geneticists in the US and Israel. The first article describes a study done by Dr. Ephrat Levy-Lahad at Shaare Zedek hospital, who concluded that ALL Ashkenazi (Eastern European) Jewish individuals should be tested for BRCA mutations—not just those individuals with family histories of breast and/or ovarian cancers. Since about 1 in 40 Ashkenazis will carry a cancer-predisposing BRCA mutation, genetic testing was suggested for everyone at a young age.  Then, in case a mutation is present, it is better to find out at a preventable stage.

The second article quotes the scientist who discovered BRCA’s association with cancer and who partnered on the Israeli study, Dr. Mary –Claire King. Dr. King’s statements took this one step further, as she called for screening all American woman 30 or older regardless of race or ethnic background—not just Ashkenazis!

Our inboxes have been flooded and the phones have been ringing all week with inquires about these articles.  So how do we feel about these statements? If you have been listening to the news, the media made it sound like these are new ‘guidelines’ or ‘recommendations,’ but we prefer the word ‘opinions.’ These opinions come from a good place, where people want to prevent illness, but they are also somewhat controversial and may be considered by some to be extreme.

For starters, we think it is important to take a step back and spell out what’s so important about BRCA in the Jewish community.  After that, we will get to the “PJGH response” to these studies.

We have spoken about BRCA many (many, many!) times in this blog, but we never actually told you why it is related to the Jewish community (our oversight!). BRCA1 and BRCA2 mutations (mistakes in the genes) cause a significantly increased risk for breast and ovarian cancer, as well as some other cancers.  Just like there are certain mutations for other diseases that are more common in the Ashkenazi Jewish population, there are three specific mutations in the BRCA genes that are more commonly found in the Ashkenazi Jewish population. Numerous studies have found that between 1 in 40 and 1 in 100 Ashkenazi Jews will carry one of those three BRCA mutations and are therefore likely at an increased risk for cancer. If someone is Ashkenazi Jewish and has a BRCA mutation, the vast majority of the time, it is one of those three mutations. Furthermore, that 1 in 40 – 1 in 100 carrier frequency holds true regardless of personal or family history of cancer. So if you take any random group of 100 Ashkenazi Jews, 1 or 2 of them is likely to carry a BRCA mutation, even if he/she doesn’t have a personal or family history of cancer.

This is a big deal, and it’s a huge community issue.

So what is our current response?

Updating Your Carrier Screening

update carrier screening croppedWhen I was at a recent sisterhood event at my synagogue, a friend of mine approached me to ask if she should “do her genetic testing again” since she and her husband were first tested in 2007 and have not been tested since. I answered with an emphatic “YES!” I appreciated that she knew to even ask this question, but our conversation got me thinking. Do other people know that new diseases are regularly being added to the Ashkenazi  Jewish panel?

The best time to get screened is well before a pregnancy. Since the 1980s when Tay-Sachs testing was introduced to the Ashkenazi Jewish world, there has been much progress in the realm of genetic testing. Currently, we screen for about 18 diseases that are common in this population. And testing for Sephardi and Mizrahi Jews as well as Jews of mixed ancestry has become more commonplace. But someone who was tested in 2001, for example, and was negative, is not “in the clear” since many more diseases have been added to the panel since then.

Many people ask me, “If I am already married, why should I bother updating my testing? It will only make me more anxious as I continue having children.” My response is that I’d rather find out that you are both carriers of the same genetic disorder by doing a blood test, rather than finding out after you have an affected child. There are other options besides for stopping childbearing, rolling the dice with each pregnancy, and breaking up! Other family planning options include testing the fetus early in the pregnancy, using an egg or sperm donor, and adoption. In-vitro fertilization with pre-implantation genetic diagnosis (PGD) is another great alternative for couples who want to know their child’s genetic status before it is even in-utero. By doing genetic testing this early on, a couple will avoid getting pregnant with an affected embryo and will circumvent any ethical or issues related to Jewish law that may arise.  Robin’s Story, a short public service announcement on, will open your eyes as to the importance of updating your screening and learning your options. And be sure to register to watch Dr. Lieman’s longer webinar about PGD and Chani’s lesson about preconception carrier screening!

Finally, while testing for diseases that are common in specific populations is currently recommended by professional genetics groups, there are labs who are now offering screening for many more diseases. These expanded carrier screening panels claim to be “one size fits all” and are marketed to all ethnicities, but a negative result on a broader screening does not fully eliminate the risk of having a child affected with one of the tested disorders, it only reduces the risk. Furthermore, expanded carrier screening does not cover all diseases that could affect offspring.

I wish I could go into every synagogue, preschool, sisterhood, and other places where women in their childbearing years hang out to remind them to update their carrier screening! But since that is impossible, please take the time to mention it to your family and friends and help me spread the message. Let’s avoid heartache together!

Your Genes are not (always) your Destiny

crystal ball It seems that over the course of any medical show series on TV, there will inevitably be a character who has     been tested for the genetic condition called Huntington’s disease (HD). I’ve seen it a million times between        ER, Grey’s Anatomy, and House, but recently I have even seen it even in the non-hospital setting on           Breaking Bad. In fact, when I googled it, I even came across a Wikipedia page called “List of Huntington’s     disease media depictions.”

So why is Huntington’s such an appealing topic in the media? Well, for starters the progression of the disease is so steep, that it is startling.Huntington’s is a neurodegenerative disorder that affects muscle coordination and leads to cognitive decline and psychiatric problems starting at around age 40. Life expectancy in HD is generally around 20 years following the onset of visible symptoms and there is no treatment or cure. When I was in grad school, I visited the Huntington’s Disease Unit at Terence Cardinal Cooke Health Care Center. I remember meeting a woman who was in her 50s who used to be a law librarian, and also a 40-something year old man who was a former judge in the New York State Supreme Court.Both were obviously very intelligent individuals, but were now experiencing severe muscle jerks called chorea, dementia, and disturbed behavior, among many other neurological problems. I remember leaving the unit that day and calling my husband on my way out to warn him that I would be in a depressed mood.

Huntington’s disease is “100%, or completely, penetrant,” which means that people who have the genetic mutation at birth will definitely develop the disease to some degree at some point in their lives. The interesting thing is that these people are not surprised when it happens to them, because only people who have affected parents will be affected. Affected individuals have a 50% risk of passing the disease mutation to each of their children. So while not all children of affected individuals will inherit the disease, if you do have Huntington’s, you have inevitably seen one of your parents suffer from it before. There are many ethical issues that arise in the realm of genetic testing in Huntington’s families–issues such as when to test an individual, determining the psychological well-being of the individual prior to testing, disclosing this information to partners, and doing prenatal diagnosis with the possibility of selective abortion, to name a few. The combination of the disease course, severity, and these ethical issues obviously makes for good plot lines.

Luckily, most genetic diseases are not 100% penetrant. Individuals who carry the genetic mutation for diseases with “incomplete, or reduced, penetrance” are not guaranteed to develop the disease. Incomplete penetrance often is seen with familial cancer syndromes. For example, many people with a mutation in the BRCA1 or BRCA2 gene will develop breast or ovarian cancer during their lifetime, but some people will not. Individuals with a mutation in a mismatch repair gene associated with Lynch syndrome are likely to develop colon cancer and other GI-related cancers, but this is not definite. Doctors cannot predict which people with these mutations will develop cancer or when the tumors will develop. These familial cancers also may appear to “skip” generations due to incomplete penetrance.

While there is, at this time, nothing that can be done to prevent Huntington’s disease, the good news is that individuals with BRCA or Lynch-related mutations can take actions to reduce their risk of developing cancer.  Carriers may consider risk-reducing surgeries: female BRCA carriers may have mastectomies and/or oophorectomies, and some many individuals with Lynch syndrome will have colonic resections. Additionally, these carriers will increase surveillance with more rigorous screenings (think mammograms and colonoscopies), and many will try to alter their lifestyle with diet and exercise.

Isn’t it encouraging to know that all the stuff you’ve inherited from your parents (the good and the bad) is  not necessarily your fate?

The “Other” Genetic Test

Fragile-X-infographic-400-square-300x300When people inquire about how many diseases are on our Ashkenazi panel, we tell them that we currently offer screening for 18 conditions that are distinctly Ashkenazi , plus another two that are common in all populations. I have already blogged about spinal muscular atrophy, the first of those “extras”.  Today I want to review why screening for the other one, fragile X syndrome, is more complex.

Fragile X syndrome is the most common inherited form of mental retardation in boys. Affected individuals demonstrate varying degrees of intellectual and behavioral disability, sensory disorders, connective tissue problems, and physical features. About 1 in 250 women are carriers of fragile X syndrome.

When we offer fragile X screening in our clinic, we find that some patients decline. This is because fragile X carrier screening is not the same as screening for the other 19 autosomal recessive conditions. Why?

Firstly, fragile X syndrome is not recessive; it is X-linked. In the context of pre-conception screening for the next generation, only females are screened for fragile X syndrome.  If you are a carrier of an X- linked disease, you are at risk to have an affected child, regardless of your partner’s results.  Therefore, finding out that you a carrier of an X- linked disease may have a more significant impact than finding out you are a carrier of a recessive disease.

Secondly, fragile X carriers may have certain health issues. While we usually tell our patients that being a carrier has no impact on your health, this may not be true of fragile X carriers. Female premutation carriers have a 20-30% risk of developing “primary ovarian insufficiency.” This condition may lead to infertility and/or early menopause.  Male premutation carriers have a 30-40% risk for Fragile X Associated Tremor/Ataxia syndrome (FXTAS), which is often compared to Parkinson’s disease. Female fragile X carriers can develop FXTAS as well (~8% risk), however it is more common in males. So while carriers will not develop fragile X syndrome, they may at risk to develop other medical conditions. Some people want to learn more about their own health risks, while others come in to learn about their offspring only.

Finally, fragile X screening results may not be as simple as “carrier” or “non-carrier”.  I am not going to go into a detailed lesson about the fragile X mutation in this blog, but the take home message is that one may be identified as an “intermediate carrier,” which is basically a pre-carrier. This person is not a carrier, so her child will most likely not be affected with fragile X. But the mutation may change over time, causing generations down the line to become true carriers ( what we call “premutation carriers”). Some patients are confused as how to proceed with prenatal or preconception genetic testing when they learn they are intermediate carriers.

So you can see why fragile X screening is not so simple. Currently, the American College of Medical Genetics and Genomics only recommends screening women for fragile X if there is a family history of it or any other form of mental retardation, or if the patient asks for it. There is no doubt that getting screened may be helpful for family planning purposes, but it may come with a price tag of more information than you had initially wanted.

To learn more about fragile X syndrome, visit the National Fragile X Foundation. They have a fantastic infographic about fragile X (part of which is shown at the top of this blog).

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