BRCA in Women

About 12.5% of women in the general population will develop breast cancer sometime during their lifetimes, but for women who carry a mutation in the BRCA1 or BRCA2 genes, the risk of developing breast cancer as well as several other cancers is much higher. These cancers also can occur at a younger age on average, may be more aggressive, and in some cases, more resistant to treatment, than other cancers. If you do not know much about BRCA1 and BRCA2, you can check out the BRCA Basics page on this site for more information.

This site focuses on BRCA gene mutations in the Ashkenazi Jewish population. About 90% of carriers in the Ashkenazi Jewish population carry one of the following three mutations, so so-called “founder mutations”: BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT. The tables below detail the risk profiles for BRCA1 and BRCA2 carriers.

Please note that these are statistics – it is impossible to predict who will develop a cancer and who will not. Everyone’s personal risk of cancer varies depending a wide variety of factors. For instance, in female BRCA carriers, the risk of breast cancer has been found to increase with the number of first-degree relatives with breast cancer (such as a parent or sibling) or second-degree relatives (such as a cousin) with breast cancer. This why it is always important to discuss you personal family history of cancer with a genetic counsellor, who can help you understand your risk and make appropriate decisions about how to manage it and prevent cancer. Studies suggest that knowing if you have a BRCA mutation or not improves breast cancer outcomes, such as early diagnosis and survival.

You can also learn more about BRCA and Jewish women through the Your Jewish Genes resource by Sharsheret.


BRCA1

There are two primary BRCA1 genes found in the Ashkenazi Jewish population: BRCA1 185delAG is the most common BRCA1 mutation and BRCA1 5382insC is the less common BRCA1 mutation. Both are similar in terms of their cancer risks (reported below), but there is some evidence over limited data and older studies that BRCA1 185delAG carriers are at a lower risk of ovarian cancer than BRCA1 5382insC carriers. It is important to note that the risk is still considered significant and that all female carriers of BRCA genes are advised to consider options for preventing ovarian cancer, which is difficult to detect and often only diagnosed once it has already reached an advanced stage. 

Breast Cancer

  • The lifetime risk for a woman with a BRCA1 mutation is about 65% compared to 12.5% on average.
  • There is an increased lifetime risk of a second breast cancer (not reappearance of first tumor). The lifetime risk is about 40% for BRCA1.

Ovarian Cancer

  • The lifetime risk of ovarian  cancer for a BRCA1 carrier is about 40% compared with 1.3% on average.

Other Cancers

  • There is a slightly increased risk for a rare form of aggressive uterine cancer, the estimated risk (to age 70) is less than 5%.
  • The lifetime risk of pancreatic cancer is about 5% compared to 1% for an average risk person.
  • Some research suggests that BRCA1 mutations BRCA1 carriers are at 4 times the lifetime risk of colorectal cancer. They may also be at increased risk for all cancers, such as laryngeal and stomach cancers, and melanoma (average 2.6 times the risk). However, because these studies are not conclusive, genetics experts often look at a person’s family history of cancer to help people with BRCA1 mutations understand their risk.


BRCA2

BRCA2 6174delT is the primary ‘founder mutation’ carried in people of Ashkenazi Jewish heritage. Half of all BRCA carriers in the Ashkenazi Jewish population will carry this mutation.

Breast Cancer

  • The lifetime risk of breast cancer for a women with a BRCA2 mutation is estimated at 45 – 55% compared to 12.5% on average. Some older studies suggest 6174delT carriers are only at 33% lifetime risk (by age 70) for breast cancer, however, this data is considered very limited at the moment and further studies are needed to substantiate these claims. All female BRCA carriers are advised to consider options for preventing breast cancer.
  • There is an increased lifetime risk of second breast cancer (not reappearance of first tumor). The lifetime risk is about 26% for BRCA2.

Ovarian Cancer

  • The lifetime risk of ovarian cancer for a BRCA2 carrier is 10 – 20% compared with 1.3% on average. Some older and limited studies suggest that 6174delT carriers average 20% lifetime risk (by age 70) for ovarian cancer, which is considered to be on the high end of risk for all BRCA2 carriers.

Other Cancers

  • The lifetime risk for pancreatic cancer for a person with a BRCA2 mutation is about 5% compared to 1% on average.
  • Research on how mutations in the BRCA2 gene affect cancer risk is ongoing. Some research suggests that BRCA2 mutations are at 12 times the lifetime risk of lymphoma. BRCA2 may also increase risk for all cancers, such as laryngeal and stomach cancers and melanoma (average 1.8 times the risk). However, because these studies are not conclusive, genetics experts often look at a person’s family history of cancer to help people with BRCA2 mutations understand their risk for additional cancers.