BRCA Basics

What everyone should know

There is up to a 1 in 40 risk of carrying gene mutations (errors) known to increase the risk of genetically driven cancers in people with Jewish heritage* and a 50% chance of a carrier passing a mutation to children – the BRCA genes.

  • People of any gender** should consider getting tested – BRCA gene mutations are best known for increasing the risk of breast and ovarian cancers in females, but they also significantly increase the risk of many other cancers that affect people of all genders, including males.

  • The best time to get tested is before cancer develops – testing for BRCA gene mutations in your 20s and 30s provides you with many options to prevent and manage your risk of a genetically driven cancer.

  • Testing is convenient, easy, and free (in most cases) current testing options include comprehensive gene testing through BC’s MSP-covered Hereditary Cancer Program and free BRCA-only testing through the new fully-funded Jewish BRCA Testing Program. It involves providing a saliva or blood test either in person or by mail. It may or may not involve genetic counselling, depending on your personal or family cancer history.

  • All people with Jewish heritage* should consider getting tested – just because there is not a strong history of cancer in your family, does not mean you are not at risk. Only halfof all Ashkenazi Jewish BRCA+ carriers have a family cancer history that would suggest the presence of a BRCA gene mutation.

*Jewish heritage is defined as having a minimum of 1 grandparent of Jewish (Ashkenazi, Sephardic or Mizrahi) ethnicity or origin.

**In all references, gender (male, female, etc.) refers to sex assigned at birth.

What are the BRCA genes?


BRCA1 and BRCA2 are important genes in the human genome. They were named BRCA (pronounced “brak-ah”) when they were discovered in 1990 to play a significant role in the development of breast cancer (BR for breast, CA for cancer), also known as Hereditary Breast Ovarian Cancer Syndrome (HBOC)

They are known as “tumor suppressor proteins” which normally control cell growth and cell death. These genes are important because they also help repair normal and abnormal damage to our DNA. Everyone has two copies of these genes in the DNA of every cell in their body. People are called carriers of BRCA1 or BRCA2 when they carry an abnormal or mutated copy of either one of these genes. That means that one copy of the gene still functions normally to help suppress tumour development.

How does having a mutated copy of BRCA1 or BRCA2 increase the risk of cancer?


Having two copies of normally functioning genes is very helpful because if one gene mutates spontaneously, as genes do across the lifespan, there is another copy to act as a backup and keep everything functioning normally. People who are carriers of BRCA1 or BRCA2 only have one functioning copy of these genes, which means if the other copy mutates spontaneously, it can lead to the development of a tumour.

 Possible causes of spontaneously mutated BRCA genes include chemical, physical, or biological environmental exposures or chance errors in cell replication. This is why having a BRCA mutation does not guarantee that a person will develop cancer. It simply means that they have a higher-than-average risk of developing cancer.

What are the cancer risks for BRCA1 or BRCA2 carriers?


This is not a simple question and the answer depends on whether you are biologically male (XY) or female (XX), your age, what specific type of mutation you have, and many other factors. Generally speaking, carriers of BRCA1 and BRCA2 may be at increased risk of developing the following cancers:

  • Breast cancer (high risk in women; increased risk in men)

  • Ovarian cancer (in women only)

  • Prostate cancer (in men only)

  • Pancreatic Cancer

  • Small, but increased risk of several other cancers including melanoma, endometrial, laryngeal, colorectal, gastric cancers and lymphoma

Of importance is that carriers are also at higher risk of developing cancer at a younger age on average and the cancers that develop can be more aggressive and resistant to conventional treatments. However, knowing one’s BRCA carrier status can not only provide them with access to many preventative measures  (whether you are biologically female or male) to avoid cancer, but it can also help doctors identify the most appropriate treatment options and even provide access to specialized cancer treatments only shown to be effective for BRCA+ individuals. It also provides important information for your family, as this gene mutation could be carried by other family members and can be passed on to your children.

You can find out more information about the risk of various cancers for male carriers here and female carriers here.

What is the risk of carrying the BRCA1 or BRCA2 genes for people of Ashkenazi Jewish heritage?


In the general population, the risk of carrying BRCA1 or BRCA2 is approximately 1/400. In people of Ashkenazi Jewish descent, the risk is about 10 times greater than in the general population – about 1 in 40 or 2.5% of Ashkenazi Jews. Most carriers in the Ashkenazi Jewish population carry one of three specific mutations of BRCA1 or BRCA2. About 90% of carriers carry either BRCA1 185delAG, BRCA1 5382insC, or BRCA2 6174delT. Knowing which mutation you have as a carrier can be important for understanding your risk profile for various cancers.

What if my family is not religious or I’m not ‘fully’ Jewish? Does this change my risk?


The increased risk of carrying BRCA1 or BRCA2 is a Jewish (genetic) heritage issue, not a religiosity issue. People who carry these gene mutations may not be actively affiliated in any way with Judaism. They may even be completely unaware of any Ashkenazi Jewish heritage, due to various historical and political events. Of course, coming from a mixed background will decrease the chances that you might have inherited these genes, but it will not eliminate the risk. Anyone who believes they may have parents, grand-parents or even great-grandparents of Ashkenazi Jewish descent should discuss the possibility of genetic testing with their family doctor or another trusted health professional.

Can I pass BRCA mutations on to my kids?


We receive one copy of our genes from our mothers and one copy from our fathers (except for sex-linked genes). Because carriers have two copies of BRCA1 and BRCA2 genes (in most cases, one normal and one mutated), which are not sex-linked, children of carriers have a 50/50 chance of inheriting a copy of these genes from their parents, if either parent carries the gene. This is why it’s just as important for biological males to know their carrier status as it is for biological females. Not only are men who carry a BRCA gene at increased for cancers like prostate or pancreatic cancer, but they can also pass these genes on to their daughters or sons.

Why is the risk of carrying BRCA1 or BRCA2 so much higher for people of Ashkenazi Jewish heritage than the general population?

BRCA1 and BRCA2 mutations in the Ashkenazi Jewish population are sometimes called founder mutations and are thought to result from a combination of two population phenomena termed the founder effect and bottlenecking events.

 Founders are a small group of people who, due to factors that create geographic or religious isolation, mate in isolation. The founder effect is when a small group of people interbreed over many generations, specific rare mutations can recur and become more common in the population.

In the case of the Jewish population, the founder effect is also linked with so-called bottlenecking events, which are related to historical religious persecution. The primary bottlenecking event that created the founder effect related to the BRCA genes in the Ashkenazi Jewish population has been traced back to the time of the Christian crusades, which wiped out approximately 98% of the population of Jerusalem, resulting in only 350 survivors. Evidence suggests that these surviving founders carried the three known “founder mutations” in the population.

This information has practical meaning when it comes to genetic testing because some laboratories now offer "ethnic-specific" mutation panels. Rather than searching through the entire gene every time a person is tested, in some cases, laboratories can instead first look for specific mutations based on a person's ethnic background

 


Still have more questions? Check out the FAQ from our recent webinar “Your Jewish Genes” or be sure to sign up for one of our upcoming online education events.