Answer Your Genetics Questions

Answer Your Genetics Questions

What are BRCA1 and BRCA2 gene mutations?

BRCA genes are normal genes that all of us have.  They function to maintain the integrity of our DNA.  Individuals who have inherited a mutation in BRCA1 or BRCA2 have a significantly increased risk for developing breast and ovarian cancer. There is also a somewhat increased risk to develop other cancers such as pancreatic, male breast and prostate cancer as well as melanoma, depending on which gene is involved. 

Approximately 1 in 40 individuals of Ashkenazi Jewish descent carry an altered BRCA1 or BRCA2 gene, compared to approximately 1 in 400 individuals in the general population.  BRCA gene mutations have also been found in Jews of Sephardi descent as well as in individuals of all ethnic origins.  In families with an inherited predisposition, cancers may occur in several family members and at younger ages than usual.

What does it mean when a tumor is genetically tested?

Whenever cancer develops, it is a result of changes in DNA that occur in a particular line of cells.  These DNA changes are not inherited, but accumulate slowly over time in cells, and can gradually change the way the cells function.  Eventually, these changes can lead to the development of cancer.  The DNA changes may be the result one’s lifestyle or habits, or may be related to an environmental exposure. Often, they happen by chance.

It helps physicians treat cancer if they know the specific DNA changes that have accumulated to cause the tumor.  We call this biomarker testing, in order to differentiate it from genetic testing for inherited mutations.  Most of the time, changes identified by this method are not inherited.

How do BRCA mutations affect the risk of breast and ovarian cancer?

Both men and women can carry a BRCA mutation and will have a 50% chance of passing it to each of their children. Not everyone who inherits the mutation will develop cancer, but the risk is increased.

For those carrying mutations, the risk for breast cancer may reach 60-80% and for ovarian cancer, 11-53%, compared to the average woman’s breast cancer risk of 12% and ovarian cancer risk of 1-2%. The risk for pancreatic cancer is 2-5%; the risk for melanoma is 3-5% with BRCA2 only. For men, the risk for male breast cancer is 1-8%, and the risk of prostate cancer is 15-30%.  In general, BRCA1 has higher risks for ovarian cancer relative to BRCA2; BRCA2 has higher risks for pancreatic, prostate and male breast cancer compared to BRCA1.

Where can I get more information about BRCA gene testing?

Before having genetic testing, you should first speak with a genetic counselor. Genetic counseling can help you understand what testing may be most appropriate for you and help you understand how the information can be useful to you. You can find genetic counselors through physicians, major medical centers’ genetics programs, cancer centers, or the National Society of Genetic Counselors at

Should men consider being tested for BRCA mutations?

Yes, men do develop cancer related to BRCA mutations, although their risk is lower than the risk for female mutation carriers.   Men with a BRCA mutation also have a 50% chance of passing it to each of their children.  

How can I prepare for my genetic counseling appointment?

Prepare for your appointment by providing a detailed family history, including information and medical records about family members who have had cancer. Bring test results from all members of your family who have had genetic testing, especially if they are positive for the presence of a mutation.

What if I test positive for a BRCA mutation?

A positive test result indicates that you have inherited a known mutation in the BRCA1 or BRCA2 gene, which provides information about your risk of developing cancer. It cannot be used to predict if cancer will actually develop—or when.  Female mutation carriers have a number of options they can consider to manage their risk (including screening, risk-reducing surgeries, and medications that reduce cancer risk), and they should discuss the options with a health care professional.  Male mutation carriers may also benefit from increased cancer screening. 

Do I need further genetic testing if my results of testing for BRCA1 and BRCA2 are negative?

If you tested negatively for a BRCA1 or BRCA2 mutation, it may be useful to consult with a certified genetic counselor about the utility of additional genetic testing.  A variety of genetic panels are now available to test for additional genes that predispose to breast, ovarian, and other types of cancer. These genes may cause a high or more moderate risk in a variety of cancers.  Your genetic counselor can advise which test makes the most sense based on your personal and family history of cancer. He/she may also be able to help choose the testing that your insurance company is most likely to cover.

The chart below describes some of the major genes that might be tested when hereditary breast and ovarian cancer is suspected.  They are divided into two sections, describing high risk and moderate risk genes.

High risk genes

Syndrome Name Genes Highest cancer risks Risk somewhat increased Fact Sheets
Hereditary breast and ovarian cancer BRCA1, BRCA2


Breast and ovarian cancer Male breast, pancreatic, prostate, melanoma BRCA Facts
Lynch syndrome MLH1, MSH2, MSH6, PMS2, EPCAM Colon, uterine and ovarian cancer Small intestine, gastric, urinary tract, prostate, and other cancers Lynch Syndrome Facts
Li Fraumeni TP53 Female breast cancer, sarcoma, adrenal cortical, central nervous system cancers Childhood cancers, leukemia, lymphoma, GI cancer, lung, prostate, ovarian, and other cancers Li Fraumeni Facts
Cowden syndrome PTEN Breast, uterine, and thyroid cancer Melanoma, colon, and renal cancer Cowden Syndrome Facts
Peutz Jeghers syndrome STK11 Female breast, colorectal, gastric and pancreatic cancer Small bowel, ovarian, uterine, cervical and lung cancer Peutz Jeghers syndrome Facts
Hereditary diffuse gastric cancer CDH1 Diffuse gastric cancer and lobular breast cancer Colon cancer, signet ring type Hereditary diffuse gastric cancer Facts
Neurofibromatosis NF1 Breast cancer, central nervous system cancers Leukemia, gastro-intestinal stromal tumors Neurofibromatosis Facts
Familial Adenomatous
Polyposis (FAP)
APC Colon Cancer Intestinal, stomach, skin, brain, pediatric liver  Familial Adenomatous Polyposis Facts
I1307K change in APC APC APC only I1307K  None Colon Cancer 10%  There is a unique change, or risk allele in the APC gene
called I1307K, and does not cause Familial
Adenomatous Polyposis (FAP). About 6% of
Ashkenazi Jews will have this change. With the I1307K
risk allele, there will be more than the usual chance
for colon polyps, and the risk of colon cancer is about
10%. National guidelines recommend that people
with this risk allele start having colonoscopies at an
earlier age, somewhere around age 35 – 40, and
continuing every 2 – 5 years, depending on findings
and family history.

Moderate risk genes

Genes Moderate risk Possible other risks Fact Sheets
ATM Breast cancer Pancreatic cancer, ovarian cancer ATM Facts
BRIP1 Ovarian cancer Breast cancer BRIP1 Facts
CHEK2 Breast cancer Colorectal cancer CHEK2 Facts
PALB2 Breast cancer Pancreatic cancer, ovarian cancer PALB2 Facts
RAD51C & RAD51D Ovarian cancer Breast cancer RAD51C & D Facts

If genetic testing is negative, how should I be monitored?

Your health care team can help you determine the best methods for monitoring breast and ovarian health. They can also keep you apprised of developments in genetic research and testing as it becomes available. A strong family history of cancer cannot be ignored even if you do not have a 
BRCA1 or BRCA2 mutation, since researchers have not yet identified all mutations or genes involved in hereditary cancer.

As a cancer survivor, what are the benefits of genetic counseling and testing?

If you have been diagnosed with breast cancer or ovarian cancer, test results may influence your surgery and treatment decisions. Genetic testing can help you make decisions about ongoing screening and inform discussions with your family about potential inherited risks.

Should I get BRCA testing even if I do not have a family history?

According to the National Cancer Institute, genetic testing of individuals who have not been diagnosed with cancer is indicated when there is an existing family history.  BRCA testing may be considered for anyone of Ashkenazi Jewish descent, with or without a known family history.  There are also individuals who, for a variety of reasons, may not have access to their family history.  While insurance does not pay in all of these cases, the cost of genetic testing has come down significantly.

Whether or not you have a known family history, are of Ashkenazi Jewish descent, or simply have questions about genetic testing, Sharsheret recommends that you speak to a genetic counselor to assess your risk, become better informed, and discuss your options.  The Sharsheret support team is available to help you address your questions and find a genetic counselor.

To speak with a member of our support team and get connected with Sharsheret’s genetics program, click here.

For additional BRCA Genetics resources, click here.