Known Genetic Risk Factors

Currently, we know about several genes that play a role in the hereditary cases of breast and ovarian cancer. Some of the genes that have already been identified include: BRCA1, BRCA2, p53, PTEN, MLH1, MSH2.  The known genes account for only about 30% of hereditary breast and ovarian cancer families.  The genetic basis of the risk in most high risk families still remains unidentified.  This study aims to define the breast and ovarian cancer genetic risk factors for the remaining 70% of high risk families.  Identification of these yet unknown genetic risk factors is essential to quantifying risk and, therefore, making the appropriate medical management recommendations for these families. 

This page provides a brief summary of what is known about hereditary breast and ovarian cancer.

As noted on the page about non-genetic risk factors, only about 5-10% of cancer is thought to be hereditary in nature.  Families with a hereditary predisposition to breast and ovarian cancer have certain characteristics, such as:

  • Several people on the same side of the family with the same or a related cancer (ie. breast or ovarian cancer)
  • Cancer in every generation of the family
  • Early age at diagnosis of cancer (typically younger than 50 years old)
  • Multiple primary cancers within a single individual, for example, bilateral breast cancer or breast and ovarian cancer in the same woman.
  • Any cases of male breast cancer or ovarian cancer in the family

Here is an example of a family tree, or pedigree, that suggests a hereditary predisposition to breast and ovarian cancer.  The patient presenting for genetic counseling is indicated by the arrow.  As you can see, her father was diagnosed with breast cancer at age 63, and she has two paternal aunts diagnosed with cancer - one with ovarian cancer and one with breast cancer.  Her paternal grandfather's sister, her great aunt, also had a history of breast cancer. 

When an individual comes from a family which is suspected to carry a hereditary predisposition to cancer, they may be referred to a genetic counselor for a complete cancer risk assessment.  During the counseling session, the genetic counselor will review the personal and family medical history, will discuss information about cancer genetics, and possibly will offer clincial genetic testing to the patient.  Also, the genetic counselor will discuss the risks, benefits, and limitations of testing, and provide an assessment of the likelihood that the family history of cancer will be explained by the genetic testing that is currently available.  Below is an overview of some of the information that might be discussed during a counseling session.

It is important to note that we all have the genes listed above, and we inherit two copies of each gene – one from our mother and one from our father. These genes are present in every cell of our bodies.  A mutation, or change, in one copy of any one of these genes may result in failure of the gene to function properly.  Having one non-working copy of the gene is what causes an increased risk of cancer.

Mutations in these genes can be passed on from parent to child.  For example, if a man or woman is known to have a mutation in the BRCA1 gene, then his or her siblings and children (including males) each have a 50% chance of also carrying the same mutation.

Some of the known genetic risk factors that account for hereditary breast and/or ovarian cancer are listed in the table below.

 

Mutations in the BRCA1 and BRCA2 genes are currently the two most common high risk genetic factors linked to hereditary breast and ovarian cancer. Mutations of these genes are known to occur at a higher frequency in individuals of Ashkenazi Jewish ancestry.  

While mutations in BRCA1 or BRCA2 increase the chance to develop cancer, not every person with a mutation will get cancer. The likelihood that an individual with a mutation in the BRCA1 or BRCA2 genes will be diagnosed with breast or ovarian cancer by about the age of 70 years is outlined in the table below.

 

BRCA1 Mutation

BRCA2 Mutation

Breast cancer

50-85%

50-84%

Ovarian cancer

20-63%

10-27%

Another primary breast cancer that follows first diagnosis

40-50%

30-50%

When a BRCA1 or BRCA 2 mutation if found, various medical management options will be discussed with your doctor and genetic counselor.  Generally, these options include:

  • increased screening for breast and ovarian cancer for early detection of cancer,
  • surgery to reduce the risk of a future cancer,
  • medication to reduce the risk of a future cancer.

Deciding on the appropriate medical management for you is a very personal choice and will vary from person to person.

A comprehensive discussion with your healthcare providers about such options is essential.

If you are interested in clinical genetic counseling, our coordinating genetic counselor, Lauren Carpiniello, MS, CGC, would be happy to meet with you or help you to find a genetic counselor in your area.  To make an appointment with Lauren, please call our office at 212-263-5746.