Understanding BRCA Gene Mutations: Your Resource Guide

By Patricia Thangaraj

What are BRCA1 and BRCA 2

BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2) are genes that produce proteins that help repair damaged DNA. The breast cancer susceptibility genes known as BRCA1 and BRCA2 are specific genes found in human DNA. Both women and men and women can inherit BRCA (an abbreviation for breast cancer, often pronounced bracka) genes from their parents.

Both BRCA1 and BRCA2 tend to be tumor suppressor genes. This is a type of gene that makes a protein called a tumor suppressor protein that helps control cell growth. However, there are cases when these tumour suppressor genes do not function normally, These changes in mutations (a.k.a. changes in DNA) in tumor suppressor genes may lead to cancer, also referred to as antioncogene.

In most cases, BRCA gene mutations are inherited, or passed down from one or more generations in a family, which is why some persons tend to develop certain types of cancers. Persons who inherit harmful variants or an altered or mutated copy of the gene are more susceptible to certain cancers, namely breast and ovarian cancer. They also have a risk of developing other types of cancers including prostate, pancreatic, melanoma and, in some families, colorectal. These persons also tend to develop cancer at younger ages than people who do not have such a variant. 

The BRCA 1 and BRCA 2 Genes

Every individual has two copies of the BRCA1and BRCA2genes, one copy which is inherited from their mother and the other one from their father. Even if a person inherits a BRCA1or BRCA2mutation from one parent, they still have the normal copy of the BRCA1 or BRCA2 gene from the other parent.

Cancer occurs when a second mutation happens that alters the normal copy of the gene. When this occurs, the BRCA1or BRCA2 gene stops functioning normally. However, unlike the inherited BRCA1or BRCA2mutation, the second mutation would not present itself throughout the person’s body, but would only be present in the cancer tissue.

Persons who do not have the BRCA1 and BRCA2 gene can still develop breast and ovarian cancer. This means that some families who have a history of breast and ovarian cancer, can have mutations in one of these other genes, even if they do not have mutations in BRCA1 or BRCA2. Genetic testing, using multigene panels, can help in this regard because they look for mutations in several different genes simultaneously.

People with a strong family history of breast or ovarian cancer are more likely to have a BRCA1or BRCA2mutation. Family members who inherit BRCA1and BRCA2 mutations tend to share the same mutation. Therefore, if one of your family members has a known BRCA1 or BRCA2 mutation, other family members who opt for genetic testing should also be checked for that mutation.

BRCA 1 and BRCA 2: What’s the Difference?

Genes are the body’s sets of genetic instructions. Mutations within BRCA genes cause them to not function properly. When BRCA genes are mutated or altered, cells are not able to repair themselves. This is when BRCA mutations cause cancer.

It is important to note that mutations in the two kinds of BRCA genes will affect patients’ risk differently.

BRCA1 mutations are associated with an increased risk for:

  • Breast cancer, including an aggressive form called Triple Negative Breast Cancer
  • Ovarian cancer
  • Pancreatic cancer
  • Prostate cancer

BRCA2 mutations are associated with an increased risk for:

  • Breast cancer
  • Ovarian cancer
  • Melanoma
  • Pancreatic cancer
  • Prostate cancer


Which Gene Mutation is Worse: BRCA1 or BRCA2?

By age 70, women BRCA1 carriers have a slightly higher risk of developing breast cancer than BRCA2 carriers. Additionally, BRCA1 mutations are more often associated with triple negative breast cancer, which is more aggressive and harder to treat than other types of breast cancer. Contrastingly, men with the BRCA1 gene mutation have a 1% lifetime risk of developing male breast cancer, while those that have BRCA2 gene mutation have a 6% risk of developing male breast cancer. BRCA carriers who get ovarian cancer appear to have better survival than non-carriers in the first five years after diagnosis. This tends to occur because BRCA related ovarian cancers often respond better to chemotherapy than non-BRCA ovarian cancers.

Hereditary Breast and Ovarian Cancer – BRCA 1 and BRCA 2

Approximately 5-10% of breast cancer cases are due to an inherited gene change.  Mutations in the genes BRCA1 or BRCA2 are the most common cause of hereditary breast and ovarian cancer (HBOC). Persons with a BRCA 1 or BRCA2 mutation will have an increased lifetime risk for both breast and ovarian cancers along with other cancers.

There are certain options for these persons including risk-reducing surgeries and for some women, chemoprevention, which can reduce mortality from breast and ovarian cancers in both BRCA1and BRCA2carriers.

Since individuals with a family history of breast and ovarian cancer are at a greater risk to have a BRCA1 or BRCA2 gene mutation, they can consider undergoing genetic testing. However, prior to this, they should have a discussion with their oncologist on if this is a suitable option for them and if their oncologist believes that it is, he/she can refer that patient for genetic counseling for a more in-depth discussion on the issue. Meanwhile, persons who do not have a strong family history of being BRCA1 or BRCA2 gene mutation carriers can be referred to screening in accordance with provincial guidelines.

Hereditary Breast and Ovarian Cancer Symptoms Explained

Around 80% of breast cancer occurs intermittently. Approximately 10-15% of breast cancer are familial, which is when shared familial risk factors e.g. genes, environment, cause a higher incidence of cancer. Meanwhile, around 5-10% are hereditary, which is due to a single gene mutation. According to Genetics Education Canada: Knowledge Organization (GEC KO), harmful mutations in BRCA1 and BRCA2 appear to account for ~30% of high-risk breast cancer families. 

HBOC is an autosomal dominant cancer predisposition syndrome.  Individuals with HBOC have a high risk for breast and ovarian cancers and a moderate risk for other cancers.  However, not all individuals who inherit a mutation in BRCA1 or BRCA2will develop cancer, otherwise known as reduced penetrance and the signs and symptoms, type, and age of onset of cancer will vary within families, referred to as variable expressivity.

Prevalence of pathogenic mutations for BRCA1 and BRCA2 carriers in the general population is projected to be 1 in 300 to 1 in 500. Persons with a Ashkenazi Jewish ethnicity have a greater risk of founder mutations. These persons will have an estimated occurrence of around 1 in 50.

Men and BRCA Cancers

Even though breast cancer is more common in women, men with a BRCA1 or BRCA 2 mutation tend to be at a higher risk of developing breast cancer than men in the general population. Furthermore, men with BRCA mutations are also more susceptible to getting prostate cancer. Meanwhile, both men and women with BRCA mutations are more likely to get pancreatic cancer.

Breast and Ovarian Cancer: Collecting Your Family History

Since men and women can inherit BRCA1, BRCA2 and other mutations from their mother or their father, it is imperative that persons collect health information from both sides of their family.  This should include any information on your parents, sisters, brothers, children, grandparents, aunts, uncles, nieces, nephews, and grandchildren. Some of the areas to focus on are the types of cancers that each relative had and at what age he or she was diagnosed. For relatives who have passed away, list the age and cause of death.

Additionally, because some ethnicities such as people with Ashkenazi Jewish or Eastern European ancestry are at a greater risk for being BRCA1 and BRCA2 mutation carriers, you should also collect information on your ancestry.

These persons should discuss their concerns of being BRCA1 and BRCA2 mutation carriers if they fit into one or more of the following groups.

  • Breast cancer, especially at a younger age (age 50 or younger)
  • Ovarian, peritoneal or fallopian tube cancer
  • Triple negative breast cancer Triple negative cancers are a type of breast cancer that lack estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2)
  • Cancer in both breasts
  • Breast cancer in a male relative
  • Pancreatic cancer
  • Metastatic or high grade prostate cancer
  • Multiple cancers in the family, including breast, ovarian, high grade prostate, or pancreatic cancer
  • Ashkenazi or Eastern European Jewish ancestry
  • A known BRCA1 or BRCA2 mutation in the family

Update your family history on a regular basis, especially as more information comes to light in areas such as any new cases of breast, ovarian, or other types of cancer that have been diagnosed and remember to share this information with your doctor.

Genetic Counselling for Hereditary Breast and Ovarian Cancer: Determining If It Is An Option for You

These are certain guidelines to identify patients at high risk for HBOC. This is why it is imperative that persons share as much information as they know about both sides of their family history as well as their concerns of developing BRCA1 or BRCA2 mutations.

The GEC KO states that physicians are likely to refer you to your provincial genetic centre or a hereditary cancer program for additional evaluation if you have a family or personal history of:

  • Breast cancer diagnosis at a young age (<35-45 years) [both invasive and ductal carcinoma in situ]
  • Ovarian cancer at any age [epithelial]
  • Male breast cancer
  • Multiple primaries in the same individual e.g. bilateral breast cancer (particularly if the diagnosis was before age 50), breast and ovarian cancer
  • Breast cancer diagnosis as well as a family history of two or more additional HBOC- related cancers, including breast, ovarian, prostate (Gleason ≥7) and pancreatic cancer
  • High risk ethnicity (Ashkenazi Jewish, Icelandic) and a personal and/or family history of breast, ovarian or pancreatic cancer
  • Triple negative breast cancer diagnosed <age 60

Or if s/he has a personal

  • Probability of 10% or higher to carry a BRCA mutation

Usually eligibility criteria for genetic testing is based on clinical features that increase a person’s susceptible. However, there are still organization specific guidelines. In most cases, genetic testing is offered to the family member with the greatest risk to be a mutation carrier to increase the likelihood of detecting a mutation. For example, this might be the youngest individual with breast cancer in a family that has a history of several cases of breast and ovarian cancer.

Benefits of Genetic Testing

Some of the benefits of genetic testing if a mutation is identified (a positive test result) include:

1) Clinical intervention can enhance outcomes.

  • Risk-reducing mastectomy decreases the risk of breast cancer by at least 90%
  • Yearly magnetic resonance imaging in addition to mammography enhances the detection rate for breast cancer
  • Risk-reducing salpingo-oophorectomy reduces the risk of ovarian cancer by at least 80% and, if performed prior to menopause, can decrease the risk of breast cancer by at least 50%
  • Chemoprevention such as tamoxifen, may be considered as an option for some women in order to reduce their risks.

2) Other at-risk family members can be identified and given the necessary risk evaluations.

3) Persons can be educated on adopting the required healthy lifestyle behaviours.

If a mutation is not identified and testing was for a known familial mutation, otherwise known as true negative, then:

  • You are not considered to be at increased risk of developing hereditary cancer but you may still be at increased risk of cancer depending on your family history
  • You and your children can receive comfort of knowing your risk levels

Provincial Breast Screening Programs

Province/TerritoryHigh Risk Breast Cancer Screening GuidelinesBreast Cancer Screening ProgramAdministrative Agency
Recommendation for high risk populations

Calgary Breast Health Program
Breast cancer screening resources for healthcare providersScreeningforlife.ca – Alberta Health Services
British ColumbiaHigh risk eligibilityBreast cancer screening policyBC Cancer Agency
ManitobaWinnipeg Regional Health Authority (WRHA) Breast Health CentreBreastCheck

BreastCheck guidelines
Cancer Care Manitoba
New Brunswick New Brunswick Breast Cancer Screening ProgramNew Brunswick Cancer Network (NBCN) is a branch of the Department of Health
Newfoundland and LabradorBreast Magnetic Resonance Imaging (MRI) and High Risk Hereditary Breast Cancer (SUMMARY,PDF, November 2012

Breast Magnetic Resonance Imaging (MRI) and High Risk Hereditary Breast Cancer (GUIDELINE, PDF, November 2012)
Breast Screening Program:

Eastern Health
Central Health
Western Health
Cancer Care a program of Eastern Health
Northwest Territories Northwest Territories Breast Cancer ScreeningNWT Health and Social Services
Nova ScotiaBreast MRI Guidelines including high risk eligibilityNova Scotia Breast Screening ProgramNova Scotia Department of Health and Wellness
Nunavut  Guidelines under review
OntarioOntario Breast Screening Program (OBSP) for high risk womenOntario Breast Screening Program (OBSP) for average risk womenCancer Care Ontario
Prince Edward Island PEI Provincial Breast Screening ProgramHealth PEI
Quebec Québec Breast Cancer Screening Program | Le Programme québécois de dépistage du cancer du sein (PQDCS)  Santé et Services Sociaux Québec  
Saskatchewan Saskatchewan Screening Program for Breast Cancer (SPBC)Saskatchewan Cancer Agency
Yukon Yukon Mammography Program at Whitehorse General HospitalYukon Hospital Corporation
Table compliments of Genetics Education Canada: Knowledge Organization








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