Ashkenazi Jewish Ancestry and Hereditary Cancer Risk: What You Should Know

By Amanda Shrewsbury, MS, CGC

When someone mentions that they are of Ashkenazi Jewish ancestry in a genetic counseling appointment, the conversation almost always shifts, because the testing recommendations for Ashkenazi Jewish people are genuinely different from the recommendations for the general population.

That shift comes from a specific piece of genetic history. Roughly 1 in 40 Ashkenazi Jewish people carries a pathogenic variant in BRCA1 or BRCA2, compared with roughly 1 in 400 people in the general population. That ten-fold difference is not about anything inherent to Jewish people themselves. It is about three specific variants that became common in a relatively small founding population thousands of years ago, and have stayed common ever since. Understanding that distinction matters, because it shapes who should consider testing, what kind of testing makes sense, and how to think about the results.

This post is for anyone exploring their own Ashkenazi Jewish ancestry, anyone with family members who have tested positive for a founder variant, and anyone who has learned recently (perhaps through ancestry testing) that they have Jewish ancestry they had not been aware of. We will walk through what is known, what the testing recommendations look like, and what other genes matter beyond BRCA1 and BRCA2.

Why are Ashkenazi Jewish people at higher risk for hereditary cancer?

The short answer is a founder effect. A founder effect happens when a population descends from a relatively small group of ancestors, and any genetic variant that happened to be present in those ancestors becomes more common in their descendants than it would otherwise be. The Ashkenazi Jewish population descends from a relatively small ancestral community that lived several hundred years ago, and variants present in that founding group, including a small number of BRCA1 and BRCA2 variants, were passed down at much higher rates than the population average (FORCE, 2025).

This is important to name clearly. The elevated cancer risk associated with Ashkenazi Jewish ancestry is not a property of being Ashkenazi Jewish. It is a property of three specific DNA variants that happen to be more common in the Ashkenazi Jewish population. The risk applies to people who inherit one of those variants, and the same variants would carry similar risk in any other population in which they appeared at the same frequency.

What are the three BRCA founder variants in the Ashkenazi Jewish community?

The three Ashkenazi Jewish BRCA founder variants are:

  • BRCA1 c.68_69delAG (historically called 185delAG)
  • BRCA1 c.5266dupC (historically called 5382insC)
  • BRCA2 c.5946delT (historically called 6174delT)

These three variants account for approximately 96 percent of BRCA1 and BRCA2 pathogenic variants identified in the Ashkenazi Jewish population (FORCE, 2025; Levy-Lahad et al., 2014). The remaining four percent are non-founder variants that can also occur in Ashkenazi Jewish people but are not population-specific.

Each of these variants substantially elevates lifetime cancer risk in the same way that any BRCA1 or BRCA2 pathogenic variant does. We have a full breakdown of BRCA1 and BRCA2 cancer risks and screening recommendations in our BRCA1 and BRCA2 explained post, but the short version is that people who inherit one of these variants face significantly elevated lifetime risks of breast, ovarian, pancreatic, and prostate cancer, along with a meaningfully elevated risk of male breast cancer.

What does the 1 in 40 carrier rate actually mean?

Roughly 2.5 percent of Ashkenazi Jewish people carry one of the three BRCA founder variants. That works out to about 1 in 40, compared with about 1 in 400 in the general population, or roughly ten times more common (FORCE, 2025; Rosenthal et al., 2015).

What that means in practical terms is that in any extended Ashkenazi Jewish family, there is a meaningful chance that a founder variant is present somewhere in the family tree, even if no one has been formally diagnosed yet. Cancer risk in BRCA1 and BRCA2 carriers is high but not universal, meaning a variant can pass through several generations of a family without anyone developing cancer, only to surface in someone who happens to be diagnosed early. Testing illuminates that family history, often in ways that family medical conversations alone cannot.

Do Sephardic and Mizrahi Jewish people have founder variants too?

Yes. The Ashkenazi founder variants get most of the public attention because they were identified first and have been studied longest, but founder variants in BRCA1 and BRCA2 have also been documented in Sephardic Jewish populations (descended from Jewish communities in the Iberian Peninsula and later North Africa) and in Mizrahi Jewish populations (with origins in the Middle East).

Documented examples include:

  • BRCA2 c.8537_8538delAG (historically 8765delAG), common in Yemenite Jewish populations (Lerer et al., 1998)
  • BRCA1 Y978X (Tyr978X), found in Iraqi, Persian, and Afghani Jewish populations (Shiri-Sverdlov et al., 2001)
  • BRCA1 A1708E and BRCA2 IVS2+1G>A, identified as founder variants in Jews of Sephardic origin from the Iberian Peninsula (Laitman et al., 2011)

These variants are far less well-studied than the Ashkenazi founder variants, and the population frequencies are not as well-established. What is clear is that anyone with Sephardic or Mizrahi Jewish ancestry should make sure their genetic counselor knows about it, because the appropriate testing panel may differ from a standard hereditary cancer panel. Some labs offer extended Jewish ancestry panels that include Sephardic and Mizrahi founder variants.

Why are testing recommendations different for Ashkenazi Jewish people?

The National Comprehensive Cancer Network (NCCN) states that genetic testing may be considered for Ashkenazi Jewish people without requiring a personal or strong family history of cancer (NCCN, 2025). This is a meaningful departure from general-population testing criteria, which typically require a personal cancer diagnosis or a family history that meets specific thresholds before testing is considered.

It is worth pausing on the phrase "may be considered." It is intentional. The NCCN language signals that testing should be part of the conversation for any adult of Ashkenazi Jewish ancestry, not that everyone of Ashkenazi Jewish ancestry should be tested. Whether testing is the right choice depends on personal medical history, family history, reproductive plans, age, emotional readiness, and a number of other factors that a genetic counselor can help work through.

The rationale for considering testing more broadly in this population is straightforward. When the population carrier rate for clinically significant variants is high enough (and 1 in 40 clears that bar comfortably), waiting for someone in a family to be diagnosed before testing can mean missing earlier opportunities for screening, risk reduction, and prevention. Bringing testing into the conversation earlier, including for unaffected people, lets families act on information before a diagnosis happens, rather than after.

What about Ashkenazi Jewish ancestry on only one side of the family?

This is one of the most common questions in a genetic counseling appointment, and the answer is reassuring. NCCN testing criteria apply to people with at least one Ashkenazi Jewish grandparent, not just to people whose entire ancestry is Ashkenazi (Georgetown Lombardi, 2020).

The reasoning has to do with how inheritance works. Each grandparent contributes roughly 25 percent of a grandchild's DNA on average, which means a founder variant carried by one grandparent has a real and meaningful chance of being passed down to descendants regardless of whether the rest of the family is Ashkenazi Jewish. People who learn through ancestry testing that they have a single Ashkenazi Jewish grandparent meet NCCN testing criteria.

This also matters because the genetics does not follow cultural or religious identity. Children and grandchildren of Ashkenazi Jewish people can inherit founder variants regardless of how they themselves identify, regardless of whether they were raised Jewish, and regardless of whether the Jewish side of the family is something they grew up aware of. The DNA does not know any of that.

What other hereditary cancer genes have Ashkenazi Jewish founder variants?

Beyond BRCA1 and BRCA2, the most clinically important Ashkenazi Jewish founder variant in adult hereditary cancer is in the APC gene. The variant called I1307K (c.3920T>A, p.Ile1307Lys) is carried by approximately 6 to 10 percent of Ashkenazi Jewish people, depending on the population studied, and modestly elevates lifetime colorectal cancer risk by roughly 1.5 to 2-fold compared with the general population (Johns Hopkins Medicine, 2025; Leshno et al., 2016).

It is important to be clear about what APC I1307K is and what it is not. Most pathogenic variants in the APC gene cause familial adenomatous polyposis (FAP), a high-penetrance condition (meaning that penetrance, the likelihood that a person carrying a variant will actually develop the associated condition, is very high — most people who inherit a FAP-causing variant will develop hundreds or thousands of colon polyps and have a near-certain colorectal cancer risk if untreated). APC I1307K is different. It is a low-penetrance variant, meaning the elevated colorectal cancer risk is modest rather than dramatic, and it does not cause FAP. NCCN recommends that people who carry APC I1307K begin colonoscopy at age 40 (or earlier if there is a family history of colorectal cancer) with follow-up every five years (NCCN, 2025; Forkosh et al., 2022).

A small number of Lynch syndrome founder variants have also been documented in Ashkenazi Jewish populations, particularly in the MSH2 and MSH6 genes. These are far less common than the BRCA founder variants and the APC I1307K variant, but they are detected on standard hereditary cancer panels and managed according to standard Lynch syndrome guidelines. Our Lynch syndrome explained post goes into the details of what Lynch syndrome management looks like.

A note on recessive conditions: Ashkenazi Jewish people are also more likely to carry variants in genes like BLM (which causes Bloom syndrome) and FANCC (which causes Fanconi anemia). These are recessive conditions, meaning a person needs to inherit two variants (one from each parent) to develop the condition itself. The conditions we have been discussing throughout this post, like HBOC and Lynch syndrome, are dominant, meaning a person needs to inherit only one variant to be at elevated risk. Carrying a single variant in a recessive condition like Bloom syndrome or Fanconi anemia is generally significant for reproductive planning rather than for personal adult cancer risk, and it falls under a related but distinct kind of genetic counseling called carrier screening. If you have questions about reproductive carrier screening, a genetic counselor can help you find the right resource for that conversation.

What does this mean for non-Jewish people in interfaith families?

The same logic that applies to Jewish ancestry on one side of the family applies to interfaith families. A child whose father is Ashkenazi Jewish and whose mother is not has the same chance of inheriting a founder variant from the father as any other child of a parent who carries one. That chance is up to 50 percent for a first-degree relative of someone who carries the variant.

This becomes important when families have shifted away from their Jewish heritage over generations, when adoption is part of the family story, or when ancestry testing turns up a Jewish background that someone had not previously known about. None of those circumstances change the underlying genetics. If a founder variant is somewhere in the family tree, descendants carry the same chance of inheriting it regardless of cultural identity.

What should you do if you have Ashkenazi Jewish ancestry?

The most useful first step is a genetic counseling appointment. A genetic counselor can review your personal and family history, talk through the testing options that match your situation, explain what results would and would not tell you, and help you think through the practical and emotional pieces of testing.

Testing options for someone of Ashkenazi Jewish ancestry typically come in two forms. Founder-variant testing looks specifically for the three Ashkenazi Jewish BRCA founder variants and is less expensive, faster, and sufficient for many people, particularly when family history is not significant. Comprehensive multigene panel testing looks at BRCA1, BRCA2, and a broader set of hereditary cancer genes, and is often more appropriate when there is a personal or family cancer history, when ancestry includes Sephardic or Mizrahi Jewish heritage, or when initial founder-variant testing comes back negative but suspicion remains based on family history. A genetic counselor will help you decide which approach makes sense for your specific situation.

If you have already had testing through a direct-to-consumer service like 23andMe, a genetic counselor is also the right person to help you make sense of those results. Direct-to-consumer testing for the three BRCA founder variants has become increasingly common, but the results often arrive without the context that a clinical genetic counseling appointment provides, and confirmatory clinical testing is sometimes appropriate. Our post on direct-to-consumer versus clinical genetic testing walks through those differences in detail.

A few additional resources from our blog that may help:

A story worth knowing about

For individuals of Ashkenazi Jewish ancestry, cancer genetic counseling and testing can be extremely informative. There are several founder variants that are well studied, well understood, very testable, and actionable.

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Talk with a ClearPath Genetic Counselor

If you have Ashkenazi Jewish ancestry and you want to understand what testing options make sense for you, or you have already had testing and want help interpreting your results, we are here to help.

Have a Question? Text or call us at (720) 799-0730 or email us at hello@clearpathgenetics.com.

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References

Facing Our Risk of Cancer Empowered (FORCE). (2025). Ashkenazi Jewish ancestry and hereditary cancer. https://www.facingourrisk.org/

Forkosh, E., Bergel, M., Hatchell, K. E., Nielsen, S. M., Heald, B., Benson, A. A., Friedman, E., Esplin, E. D., & Katz, L. H. (2022). Ashkenazi Jewish and other white APC I1307K carriers are at higher risk for multiple cancers. Cancers, 14(23), 5875.

Georgetown Lombardi Comprehensive Cancer Center. (2020). Cancer organization recommends genetic testing for Jewish people of Ashkenazi descent. https://lombardi.georgetown.edu/lombardi-stories/cancer-organization-recommends-genetic-testing-for-jewish-people-of-ashkenazi-descent/

Johns Hopkins Medicine. (2025). APC I1307K and colorectal cancer. https://www.hopkinsmedicine.org/health/conditions-and-diseases/colon-cancer/apc-i1307k-and-colorectal-cancer

Laitman, Y., Feng, B. J., Zamir, I. M., Weitzel, J. N., Duncan, P., Port, D., Thirthagiri, E., Teo, S. H., Evans, G., Latif, A., Newman, W. G., Goldgar, D., Couch, F. J., & Friedman, E. (2011). Two BRCA1/2 founder mutations in Jews of Sephardic origin. Familial Cancer, 10(1), 59–63.

Lerer, I., Wang, T., Peretz, T., Sagi, M., Kaduri, L., Orr-Urtreger, A., Stadler, J., Gutman, H., & Abeliovich, D. (1998). The 8765delAG mutation in BRCA2 is common among Jews of Yemenite extraction. American Journal of Human Genetics, 63(1), 272–274.

Leshno, A., Shapira, S., Liberman, E., Kraus, S., Sror, M., Harlap-Gat, A., Avivi, D., Galazan, L., David, M., Maharshak, N., Moanis, S., Arber, N., & Moshkowitz, M. (2016). The APC I1307K allele conveys a significant increased risk for cancer. International Journal of Cancer, 138(6), 1361–1367.

Levy-Lahad, E., Lahad, A., & King, M. C. (2014). Precision medicine meets public health: Population screening for BRCA1 and BRCA2. Journal of the National Cancer Institute, 107(1), dju420.

National Comprehensive Cancer Network. (2025). NCCN clinical practice guidelines in oncology: Genetic/familial high-risk assessment — Breast, ovarian, and pancreatic. https://www.nccn.org/

Rosenthal, E., Moyes, K., Arnell, C., Evans, B., & Wenstrup, R. J. (2015). Incidence of BRCA1 and BRCA2 non-founder mutations in patients of Ashkenazi Jewish ancestry. Breast Cancer Research and Treatment, 149(1), 223–227.

Shiri-Sverdlov, R., Gershoni-Baruch, R., Ichezkel-Hirsch, G., Gotlieb, W. H., Bruchim Bar-Sade, R., Chetrit, A., Rizel, S., Modan, B., & Friedman, E. (2001). The Tyr978X BRCA1 mutation in non-Ashkenazi Jews: Occurrence in high-risk families, general population and unselected ovarian cancer patients. Community Genetics, 4(1), 50–55.

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This blog post is for educational purposes only and does not constitute medical advice, diagnosis, or treatment. Always seek the advice of your physician, genetic counselor, or other qualified healthcare provider with any questions you may have regarding a medical condition or your individual health needs.