This month, the U.S. Preventive Services Task Force (USPSTF) updated their recommendations on prevention of BRCA-related cancers. The new recommendations, published in the Journal of the American Medical Association (JAMA), expand upon previous guidelines developed in 2013 and now include recommendations for individuals of high-risk ancestry.  What does this mean for Jewish women? We’ll break it down.

What is the U.S. Preventive Services Task Force?

The USPSTF is an independent, volunteer panel that provides evidence-based recommendations on what preventive services primary care clinicians should offer their patients. The Task Force assigns letter grades to each service it reviews to indicate the balance of expected benefits and harms, as well as the level of certainty based on scientific evidence.

Interventions with the grades A or B are recommended, and the Affordable Care Act requires private insurers to cover those services with no cost-sharing (i.e., there is no out-of-pocket cost to the patient). The Affordable Care Act also requires Medicaid to cover those services and authorizes Medicare to do so. 

What did they recommend before?

The USPSTF previously recommended that primary care providers screen women with a family history of breast, ovarian, tubal, or peritoneal cancer to identify whether they are appropriate candidates for genetic counseling and possibly BRCA testing.

This screening involves the clinician going through a risk assessment questionnaire or checklist. The risk assessment can identify a family history suggestive of a possible BRCA1/2 mutation. If screening indicates that hereditary cancer may run in a patient’s family, her primary care provider should then refer her to genetic counseling.

What are they recommending now, and how is it different?

The updated recommendation adds women who have ancestry associated with BRCA1/2 gene mutations and women with a personal history of breast, ovarian, tubal, or peritoneal cancer to the list of those who primary care providers should screen for hereditary cancer risk. The recommendation does not specifically mention any ethnicity or ancestry, but Ashkenazi Jewish ancestry is most strongly associated with BRCA1/2 mutations. 1 in 40 women of Ashkenazi ancestry carries a BRCA1/2 mutation compared to about 1 in 300 women in the general population.

What does this mean for you?

Primary care providers and women’s healthcare providers often already ask their female patients about family history of cancer. This recommendation encourages them to also ask about ethnicity and prior personal cancer diagnoses and use that information to initiate screening for hereditary cancer risk. If you meet the criteria, most insurance should cover this screening with no out-of-pocket cost to you. These recommendations apply to anyone assigned female at birth, as BRCA-related cancer risks are tied to biological sex.

The risk assessment screening relies on information about family health history, so the screening is most effective if you know about any history of cancer in your parents, grandparents, aunts, uncles, siblings, and children, including their age at diagnosis. You can find family health history tools on the Sarnoff Center website.

If you are a woman with Ashkenazi Jewish ancestry and you have not yet discussed hereditary cancer risk with your primary care provider, your next checkup is a great time to start the conversation—and to mention that you have Ashkenazi Jewish ancestry.

For additional information and discussion of this change see:

• Journal of the American Medical Association editorial by Dr. Susan Domchek and Dr. Mark Robson, as well as the accompanying news release
• Interviewwith Carol Mangione, member of the USPSTF

A flow chart below describes the updated recommendation.

By Elianna Miller

I feel absolutely honored to have been the Lewis Summer Intern at the Norton and Elaine Sarnoff Center for Jewish Genetics. My desire to be a genetic counselor has been strengthened, and I discovered a passion for the community that I want to implement into the workplace. I learned how empowering it can feel to provide an entire community with genetic information.

I was highly integrated into the Sarnoff Center team by contributing to the Center’s blog, working on community outreach, and analyzing data for a community wide cancer survey that was sent out before my internship began. I worked on a very high functioning team, where everyone has a different educational background and desire for the community. Everyone brings their own skill set that makes the rest of the team stronger. While being in undergrad still made me have the smallest toolbox to bring, I still saw some of my work be a part of the big picture that makes up the Sarnoff Center.

The main goal of the Center is community education and engagement. I developed a presentation on Jewish genetics to inform the other 41 Lewis Summer Interns that worked all across the Jewish United Fund and agencies. The presentation was accompanied with a pre- and post- survey to see how knowledge and attitudes changed about recessive disorders, hereditary cancers, and health history. I found that people felt engaged throughout the 30-minute Prezi, and enjoyed interactive pieces. They seemed to have gained the most knowledge on the topic of hereditary cancers, as a lot of them self-reported a great increase in knowledge on BRCA mutations. All of the post-survey respondents also noted that they now understand how important it is to obtain family health history, which is a health behavior that even college students can start doing now.

Through all these work experiences and tasks, my mind has been very widely opened. Again, I aspire to be a genetic counselor, and I now know many ways that this can look. Articulating my thoughts on the field was difficult before, but now I have enough knowledge to accurately describe my desires and passions. I am very grateful for my placement this summer and look forward to the many doors that will open because of it. As I head back to Columbus for my final semester of my undergraduate career at The Ohio State University and whatever comes next, I know that I will never forget this outstanding experience.

By Elianna Miller 

Approximately 1,762,450 new cancer cases will be diagnosed in the US in 2019. This number has grown rapidly since 2005, but what caused this increase? Is it people’s DNA, their environment, or is it just bad luck?

A lot of the Sarnoff Center’s work focuses on hereditary cancers, particularly BRCA mutations, which are 10x more common in Jewish communities than the general population. BRCA mutations are linked to breast cancer in women in men, ovarian cancer, prostate cancer, pancreatic cancer, and melanoma. The average woman’s lifetime chance of a breast cancer diagnosis is about 12%, but that increases to 45%- 87% with a BRCA mutation. Lynch syndrome is another inherited genetic disorder that can be linked to Ashkenazi Jewish ancestry, which increases the likelihood of some gastrointestinal cancers. 

If someone with a mutation such as these ends up developing cancer, it typically happens earlier in life than with the average person. Cancer predisposition genes are typically present from birth, though the actual cancer doesn’t form until later. That means there must be more to it than just genetic predisposition.

Let’s take a deeper dive into BRCA mutations. We all have BRCA genes: one copy from mom, and one from dad. If both parents give their daughter unmutated copies of the BRCA gene, she has that 12% risk of a breast cancer diagnosis in her life. The cancer risk increase happens with a mutation in one of the two copies: since only one copy of the mutation increases risk, inheritance happens in an autosomal dominant fashion.

So, why do some women with BRCA mutations develop breast (or another related) cancer, while others do not? The development of cancer in the body based on a predisposition usually manifests in a mechanism called the “two-hit theory.” The first hit is the mutation at birth, and the second hit is later in life when the cancer begins to form. The interaction of other factors, such as the environment or other genes in the body, with a preexisting cancer risk mutation may lead to or prevent cancer development.

Many environmental factors can cause a second hit. Sun or chemical radiation exposure, alcohol use, poor diet choices, the process of aging, or tobacco use are some of the most common. Sometimes, these risk factors don’t even cause mutations, they just change gene expression. Someone could live the healthiest of lifestyles, but the interaction of certain genes affects the way that tumors get suppressed. Researchers at Johns Hopkins also found that some tissues in the body are just more susceptible to “bad luck” and random DNA mutations that cause cancer.

The takeaway here is that while genetics can increase our risk of cancer, only about 5% of all cancers are due to underlying genetic causes. Of the 1,762,450 estimated cancer diagnoses this year, about 88,000 will have a direct underlying gene mutation, and almost one million cases will not. Our environment and random chance play a lot more into cancer diagnosis than one may expect; being positive for a genetic mutation that leads to cancer predisposition is NOT a diagnosis, just as being negative for one of these genes does NOT clear one of a lifetime cancer diagnosis. The team, and specifically the genetic counselor, at the Sarnoff Center is open and available to answer any questions or connect you to more resources related to cancer genetics.

Photo citation:  https://www.flickr.com/photos/genomegov/26453305264/ 

By Elianna Miller

In late 2018, “CRISPR babies” made news worldwide, and they are now coming back to the spotlight. When He Jiankui made genetically modified embryos that grew into twin girls with HIV immunity, people were outraged. He didn’t discuss his plans with his scientific community, and the procedure was deemed unnecessary and risky. These so called “CRISPR babies” were viewed with great controversy and caused a halt in the global scientific community on gene-edited embryos.

Now, Russian scientist Denis Rebrikov has announced his desire to produce CRISPR babies that can hear from parents with recessive genetic deafness. Because both parents have an altered copy of a gene related to hearing, any child they naturally conceive would be deaf, too. The participants want to provide their children with the ability to hear. Rebrikov plans to consult scientific communities and explain the benefits of the process, unlike He.

So, what is CRISPR? It’s a groundbreaking technology that is often seen in the news but less often well understood. Short for Clustered Regularly Interspaced Short Palindromic Regions, multiple repeats of the same 30 or so base pairs are separated by different genes of interest (spacers). Spacers serve as a guide for an enzyme, usually Cas9, to cut specific pieces of the genetic code. When this “faulty” DNA is cut, that gene is essentially turned off.

The cutting also acts as marking, and other molecular components can guide new DNA to that marked spot. This unfortunately doesn’t always work perfectly. Since there are so many repeats, the cutting enzyme can go to the wrong spot, editing unintentionally. Rebrikov still wants to use this process to insert “hearing genes” into embryos regardless of the imperfect mechanism.

Many ethical dilemmas arise here. There is no consensus on who gets to decide when CRISPR should or should not be used. Right now, the ability to hear is a product of environment and parental genes, and scientists like Rebrikov are attempting to change those factors with this new technology.

The Center for Genetics and Society talks about CRISPR in the context of disability rights, and the range of perspectives needed when making decisions about cutting genes from embryos. They note that removing genes linked to certain characteristics is marking them as tragic, implying impossibility of a good life. How can we respect people living with certain conditions that we are choosing to eliminate from others? Also, where do boundaries lie, and how do we draw the line on what genes can be edited? If we can edit out certain genetic disorders, what will stop us from selecting for certain eye colors, heights, or intelligence capacities? These are difficult questions that will be debated again and again as CRISPR gene editing technology advances and begins to touch more lives.

To learn more about CRISPR along with the research and ethics of it, sign up for the Norton and Elaine Sarnoff Center for Jewish Genetics’ event: CRISPR: Is Gene Editing Kosher? We will be discussing potential answers and the lack thereof for questions like these.

References: 

https://www.sciencedirect.com/science/article/pii/S216225311630049X

https://www.flickr.com/photos/genomegov/39603195652/