Reflecting on 2015, we realized that the Program for Jewish Genetic Health gave around 40 live talks over the course of the year, to a wide variety of target audiences (not to mention the online “lessons” we release on MyJewishGeneticHealth.com to a worldwide audience). In thinking about the talks I personally have given over the last few months, I realized that many times the questions come after the Q&A portion, even weeks after. Sometimes the “asker” was aware of the fact that their question was too personal in nature, other times the asker may have thought their question would seem naïve. Occasionally, the asker has been thinking for a while about the topic and comes up with an inquiry that is rather deep.
Here are two examples of recurring personal questions that I have received after my BRCA-centered talks. As a brief review, mutations in the BRCA genes predispose women and men to developing certain kinds of cancers including breast, ovarian, pancreatic, and more. BRCA mutations can run in families and be inherited by children. Women and men who are shown by genetic testing to carry BRCA gene mutations have options to reduce and manage their cancer risks. About 1 in 40 individuals of Ashkenazi Jewish descent are believed to carry a BRCA mutation, even if there is no significant incidence of BRCA cancers in their families.
Question 1: My grandmother had XX cancer and my aunt had XX cancer. Do you think I need to consider BRCA testing?
The answer to this one is easy—I always remind the asker that I am not a genetic counselor or a genetic healthcare provider, and I advise them that they should consider meeting with one of those professionals to discuss their family cancer history. A good online resource for finding a genetic counselor anywhere in the US and Canada is http://nsgc.org/p/cm/ld/fid=164 (make sure to search under the ‘cancer’ in ‘types of specialization’). I also advise them to try to collect as much family cancer history information (including cancer type and age of diagnosis) as possible, so that if they ultimately decide to pursue genetic testing for hereditary cancer, the most appropriate (and most current) test can be ordered based on that family history.
Question 2: Given the 1 in 40 carrier rate of BRCA mutations in Ashkenazi Jews, have you yourself gotten tested?
For a long time, the answer was no, I am just not ready. The decision to pursue genetic testing is a very personal one, and several factors need to be considered including whether the timing is right to deal with the knowledge and its implications. More recently, the tides have turned for me, in part due to two comments that reverberate in my mind and heart. The first is something one of our Program genetic counselors likes to say–“Finding out that one has a BRCA mutation doesn’t change anything about whether that mutation is there or not…finding out allows an individual to be empowered to consider available options.” The other is a sentence from a recent New York Times piece by the author Elizabeth Wurtzel after her cancer diagnosis and ensuing surgery and chemotherapy—“I could have avoided all this if I had been tested for the BRCA mutation.”
Part of me appreciates that audience members reserve their very personal questions at the end of (and especially during :)) my talks, since usually these questions do not have generalizable value. Maybe though, in the realm of genetics and cancer prevention, every “story” has the potential for a broadly relevant take home message.
For years, when we got inquiries from Sephardi or Mizrahi patients about preconception genetic testing, we would respond that there is currently no testing panel as there is for our Ashkenazi patients. And we would feel bad about that because we know that, like in many other ethnicities, there are genetic diseases which are common in Sephardi and Mizrahi populations too.
When we hosted a genetic testing event at Yeshiva University in 2013, our flyer included a call-out to the Sephardi students to contact us privately and not to register for the event. Turns out, 22 interested students were disqualified from the event, and I have no idea how many actually called us to come in for private counseling and testing. My guess is zero.
Since the genetics for Sephardi and Mizrahi Jews differ by country of origin (and there many countries with Jews), genetics labs never really made it a priority to develop testing panels. After all, why should they develop tests that a tiny number of people will actually need? So we were left between a rock and a hard place; on the one hand, we encourage people to get tested for diseases common to individuals of their ethnicity, but on the other hand, we are unable to order any testing. We were essentially pushing a product we didn’t have.
This all changed about a month ago, when we started offering a new panel that was developed for Jews of all backgrounds. This new panel is made of 96 diseases; 48 of them are common in Ashkenazis, 38 in Sephardi/Mizrahis, and 10 overlap between the groups (it is a very large panel!). Here are some of the things that we have been finding since we upgraded:
- People think they know what their ancestry is, but are surprised to find out they may be more mixed than they thought. A patient of ours could have sworn he was 100% Ashkenazi, but he came back as carrier for a disease that is common in Yemenite Jews. When he asked his grandmother if there was something he didn’t know, he learned that he had some North African ancestors!
- The more diseases we screen for, the more likely someone will be a carrier. We used to say that about 1 in 3 people will screen positive for something. But so far, I think we have only had one patient who was not a carrier of anything on the panel. And of course, being a carrier, in general has no effect on one’s health and should not be considered a stigma.
- Even though we have tripled the amount of diseases on our testing panel, the ‘classic’ Jewish diseases are still ‘classic.’ I would have thought that the more diseases we screen for, we would see a wider array of results, but we have been seeing that those diseases that have been on the panel since the beginning (the common ones, like Tay Sachs and Gaucher) are still the ones that we have been picking up most often.
- We have had a Jewish history lesson for our genetic counselors helping them understand the different migrations of Jews over the course of history, and how ‘Ashkenazi’, ‘Sephardi’, and ‘Mizrahi’ Jews came to be.
The bottom line is that carrier screening is recommended before contemplating a pregnancy for anyone that is at least ¼ Jewish. It doesn’t make a difference if one has mixed ancestry, if he/she knows that a relative tested negative in the past, or if he/she chooses to affiliate with a movement within Judaism. Our genes do not choose to be transmitted only to the “more Jewish” people. Most of the diseases on the panel are a burden on the affected person and the family and testing a couple before a pregnancy is one of the best preventative actions one can take to avoid heartache. Visit PJGHtesting.com to learn more about the testing.
As I was sitting down to write my newest blog post, tons of Chanukah-related themes floated through my head. But the material side of me thought of presents, and about how we spend so much time and money thinking about the perfect gift for each of our loved ones. But why do we put so much energy into this? Yes, because we love them, but it’s not completely altruistic. We want the receivers of our gifts to think good of us. I find that the gift-giving ceremony has become verification that the giver is a worthy person in the receiver’s life.
But it’s not always that way–some gifts are unselfish. I am referring to giving the gift of life via organ or bone marrow donation. I have a soft spot for the Gift of Life Bone Marrow Foundation, a registry of hundreds of thousands of donor samples that are available to be matched should an individual with a blood disorder (such as leukemia or lymphoma) need a transplant. After attending their Partners for Life Gala dinner this past summer and witnessing 3 donor/recipient couples meeting for the first time since their successful transplants, the term gift of life has taken on a new meaning to me.
Matching is done through the histocompatibility antigen test, which looks for proteins called human leukocyte antigens (HLAs). HLAs are found on the surface of nearly every cell in the human body and are found in large amounts on the surface of white blood cells. They help the immune system tell the difference between body tissue and foreign substances. Each person has two sets of 3 small, relatively unique HLA proteins that they inherit from each of their parents. Siblings have a 1 in 4 (or 25%) chance of being a match, that is, of inheriting the same two sets of HLA proteins.
After HLA is determined, a crossmatch test is used to determine whether the recipient has antibodies against the donor’s HLA. If so, these antibodies could injure the donor’s cells, making the transplant a failure.
As you can see, finding a perfect match is not easy. If a family member is not a match, then the next most likely candidate is someone from the same ethic background. The Gift of Life Bone Marrow Foundation is part of the National Marrow Donor Program, but has a niche in that it is dedicated to recruitment within the Jewish community. A Jewish individual seeking a match is more likely to find it within this smaller group of samples. This subset of samples also adds much needed ethnic diversity to the overall donor pool.
To become a potential donor, all you need to do is take a special Q-tip and swipe it in your mouth, either at home or at one of the many donor drives in your area. Gift of Life will call you if they believe you could be a match for an individual in need and will do more invasive follow-up studies.
So this Chanukah, think about giving the most selfless gift you can. What greater gift can one give to another than the gift of life?
For more information about Gift of Life or to get swabbed, visit their website at: www.giftoflife.org
A few weeks ago I had the opportunity to meet with some of the Rabbis and educators at the Manhattan Jewish Experience (MJE) on Manhattan’s West Side. MJE is a cutting edge program for young Jewish professionals in their 20’s and 30’s, with little or no background in Judaism who are interested in connecting more to each other, to their community, and to Judaism. MJE is a place where young men and women can explore Jewish life and meet new people.
Prior to our session, we had begun to discuss some of the issues related to Ashkenazi Jewish carrier screening which were unique to this community, but I was definitely not prepared for how unique the needs of this community are!
Broaching the topic of genetic testing for this community is completely different than for individuals who grew up hearing and knowing about it. Many couples who come to our office for carrier screening are already familiar with my shpiel. However for many in this community, the idea that they could potentially be at risk to have a child with a genetic disease specifically because they are Ashkenazi Jews is a completely new concept. Thinking about when is the right time to bring up the concept of Jewish genetic disease carrier screening and when the right time for having the testing done was also definitely a challenge. Especially when you are trying to make sure that these individuals and couples don’t get overwhelmed by the concern that they could have a child who is affected.
As always, there is no “cookie-cutter model” which will work for each couple and individual, but I believe the best line from our discussion was, “this doesn’t have to be stressful.” Carrier screening is, and should be seen as routine. This does not need to add on unbelievable stress for an individual or to a relationship.
We’re looking forward to working with the MJE in the future, as they continue to determine how best to approach their community on these issues.
As an Ashkenazi Jew and someone who was pregnant several times in the late 1990s and early 2000s, I witnessed, from the perspective of a patient, the stepwise increase in the number of Jewish genetic diseases for which carrier testing was available. When I moved into this scientific realm professionally in 2006, I realized that that was only the tip of the iceberg. What had started out as population testing for one disease only (Tay-Sachs) in the 1970s rapidly advanced gene-by-gene, to the point where now we readily can test for carrier status for at least 18 of the so-called “Ashkenazi Jewish genetic diseases.”
Until recently, testing was performed in a gene by gene manner, resulting in additive costs that reached the thousands of dollars. Fortunately, breakthroughs in technology have led to significant progress in reducing the costs associated with screening for many diseases at the same time. Now, a single DNA sample can be assessed on a “chip” or an “array” that simultaneously can survey many mutations in many disease genes . If a mutation is detected by the array, then that individual is said to be a “carrier” of the associated genetic disease. Remember, carriers themselves do not and will not exhibit symptoms of that disease, but offspring of carrier couples are at risk to be affected.
Okay, now here is where the “are we sure we really want to go there” question comes into play. Right now, we are still testing for the common mutations in the relevant disease genes with these “targeted” arrays. But there are other rarer mutations in those same genes that have been described to be disease-associated that are not being assessed routinely. So, some carriers are being missed. If we wanted to look at each disease gene in its entirety, we could instead be using a technology called gene sequencing. With gene sequencing, each position in the gene is “read” and then cross-compared to the normal sequence. Many companies and laboratories are thinking about/developing sequencing platforms for the purpose of carrier identification, with the goal of missing fewer carriers.
So what’s the downside? The downside is that we will not only pick up the common+rarer disease mutations, but we will also pick up changes that we cannot interpret properly because we have not seen them before (these changes are called “variants of unknown significance”). They could be disease-causing in offspring of carrier couples, but alternatively they could be benign. If we as professionals can’t interpret these properly, what do we tell the patients?
And you know what makes me even more anxious? The alternative concept of sequencing ALL of someone’s genes (their genome) for carrier identification, as opposed to just focusing the sequencing on a targeted subset of genes, such as the subset that causes the Ashkenazi Jewish diseases. In that scenario, not only will we be grappling with the variants of unknown clinical significance, but also with findings throughout the genome that are incidental/unanticipated. These findings could include mutations that lead to adult-onset disease in the carriers themselves, some of which diseases have no treatments or cures.
Only time will tell where the field is heading, and advances in technology coupled with decreasing costs may be the ultimate drivers here. I think we should pause and think about how vast the ocean is before taking the plunge.
“I’m dating this girl and we want to get engaged really soon (i.e.- tomorrow, latest next week). I figured we should do that ‘genetic testing thing’. Do you think we need to wait to get engaged until after the results come back?”
I get this question ALL THE TIME. The truth is, it depends. It depends on you, and how this information might be useful for you.
If you want your results strictly for informative purposes, i.e.- you’re going to get married no matter what, even if you are both carriers of the same genetic disease and have a 25% chance in each pregnancy to have an affected child, then no- you don’t have to wait to get engaged. There absolutely are options out there that can help you have a healthy family. I would still recommend undergoing testing sooner rather than later, because it may be useful to know what you’re getting into and begin learning about and speaking with your partner about your options before you both consider a pregnancy.
HOWEVER, if you might not continue the relationship if you and your partner are both carriers of the same condition and are at risk to have an affected child, then you absolutely should wait to get engaged. These genetic testing results could identify that you and your partner are at risk to have an affected child. After all, that’s why we do the testing to begin with. If I could tell by looking at you that you weren’t a carrier then this whole “genetic testing thing” would be a bit redundant. It is never easy to end a relationship; however it is definitely easier, and less traumatic to break up a relationship prior to getting engaged as opposed to afterwards.
Unfortunately, many people wait until the very last moment to have Ashkenazi Jewish carrier screening, as a “just in case” sort of check, and they expect (and hope) that the results will be normal. About 1 in 100 (1%) couples of Ashkenazi Jewish descent are both carriers of the same genetic disease. As far as I’m concerned, testing should definitely be done before a pregnancy, but past that, you have some leeway in terms of when you’d like the testing to be done.
Personally, I did this testing before I even met my husband. I wasn’t even dating anyone at the time. I just felt that the information would eventually be useful, and I wanted it to be there, ready and waiting for me when I needed it. Genetic testing results are different than other types of blood tests as the results do not change. Once you’ve had the testing, those results are yours and do not change from year to year. However, you should update your testing as new disorders are added to the panel over time.
Last week, Estie and I had the opportunity to head out to Stamford, Conn. and participate in the Jewish Learning Initiative on Campus (JLIC)’s annual conference. JLIC is a program run through the Orthodox Union that places Orthodox Rabbinic couples as Torah educators in Hillels on college campuses. The JLIC educators provide avenues for spiritual development and exploration for Jewish students from varied backgrounds as well as presenting a positive, sophisticated and welcoming face for Orthodox Judaism on campus.
Our goal in educating these educators was to spark their interest in issues related to genetics and Jewish law and encourage them to discuss these issues with their students. We were thankfully able to provide the JLIC educators with a list of Jewish sources discussing issues related to genetics such as pregnancy termination, invasive prenatal testing, preimplantation genetic diagnosis, confidentiality, and disclosure. These sources will undoubtedly come in handy for the JLIC educators and help them raise awareness and begin a dialogue with their students about these interesting and important issues. While raising awareness about genetics issues on campus is one step, many of the educators expressed interest in hosting a genetic screening event on their campuses for their students.
The educators had lots of really good questions ranging from what to say to students who are very anxious about undergoing carrier screening to whether or not college students are even interesting in Ashkenazi Jewish carrier screening (but more on that later)! We’re looking forward to working with them!
by Chani Wiesman, MS, CGC
A few weeks ago I joined a group of women gathered together in the study hall at Ma’ayanot Yeshiva High School for Girls in Teaneck, New Jersey to help them learn about prenatal and preconception genetic carrier screening as well as hereditary cancers and their impact on the Ashkenazi Jewish community.
These women are preparing to become Yoatzot Halacha, literally, Advisors on Jewish Law. Yoatzot Halacha are women certified by a panel of Orthodox rabbis to be a resource for women with questions regarding Taharat HaMishpachah (an area of Jewish Law that relates to marriage, sexuality and women’s health). This role was devised to assist women who are more comfortable discussing very personal issues with another woman. As part of their training, they devote two years (over 1000 hours) to intensive study with rabbinic authorities in these laws.
They receive training from experts in modern medicine and psychology, including gynecology, infertility, women’s health, family dynamics and sexuality. I spent a total of 2-½ hours with these future leaders in the Jewish community, discussing the importance of preconception carrier screening as well as awareness about the high risk for inherited cancers, specifically breast and ovarian cancer, and the availability of genetic testing, as well as screening and management recommendations for high-risk women. Yoatzot Halacha are in a unique position in the community, as they often meet with women before they get married, and have a continued relationship with women throughout their reproductive lives, making education about reproductive and cancer genetics vital.
The Yoatzot Halacha-in training had many thought provoking questions ranging from the efficacy of self-breast exams, to insurance coverage for preconception genetic carrier screening, to issues of disclosure of genetic test results to family members. They were actively thinking about the practical applications of genetics to their role in the community and how they will be able to broach these issues with the women they advise.
All in all, a wonderful experience! I look forward to working with these women more in the future.