Genetics 101

All cancer is caused by changes in genes. But in most people, these changes have occurred sporadically by chance or with age. However, some people have developed cancer, or are at high-risk of certain cancers, because of a genetic susceptibility they have inherited.

Genes are present in every cell in our body, contained in structures called chromosomes, which are found in the nucleus of a cell. We have 46 chromosomes that come in 23 pairs. One chromosome in each pair comes from our father, and the other comes from our mother. Each chromosome, in turn, is made up of thousands of genes. Genes are coded segments of DNA that, like chromosomes, come in pairs. DNA contains instructions for making the substances that help our bodies to function properly. A change in the sequence of the DNA that makes up the gene can cause the gene to stop functioning. These genetic changes are called mutations.

 Inside the Cell

What are BRCA1 and BRCA2?

Hereditary breast and ovarian cancer is caused by mutations in two genes called BRCA1 and BRCA2. These genes were discovered in 1994-1995 (the acronym BRCA comes from BReast CAncer one or BReast CAncer two). Normally these genes act like brakes that help stop abnormal cell growth in the breasts and ovaries. However errors (called mutations) can occur in these BRCA genes, and if a woman has inherited a mutation in one of these genes she has a high chance of developing breast and/or ovarian cancer. Women who carry a mutation in one of these genes may have a 50-85% lifetime risk of developing breast cancer and a 20-40% lifetime risk of developing ovarian cancer.

About 1 in every 400 people in our population carries a mutation in BRCA1 or BRCA2, and less than 5% of all breast and ovarian cancers can be explained by a BRCA mutation.

The good news is that we now have the opportunity to be proactive with our health. Unlike previous generations we have options available to us to reduce our risk or detect cancer early.

Understanding hereditary breast and ovarian cancer

A family history of breast and/or ovarian cancer is an important risk factor. A family history means having one or more blood relatives on the same side of the family diagnosed with breast and or ovarian cancer (sister, daughter, mother, grandmother, cousin, aunt, and rarely a brother, uncle or grandfather). These relatives could be on your mother’s or father’s side of the family as BRCA gene mutations are inherited equally by males and females.

Since breast cancer is common, a family history of breast cancer can also be due to chance and age. However, women with a strong family history of breast and/or ovarian cancer are likely to have inherited a BRCA mutation.

A parent with a BRCA1 or BRCA2 mutation has a 1 in 2 chance (50%, like “heads or tails”), of passing it onto each child they have. There is also a 50% chance for each child to inherit a normal BRCA gene from their parent who carries a BRCA mutation If the normal gene is inherited, you will have the same risk for breast or ovarian cancer as a person of your age in the general population.

Remember, cancer is not inherited, only the gene mutation that increases the risk of developing it.

What are the risks associated with a mutation in the BRCA1 or BRCA2 gene?

In the general population, about 1 in 12 women will develop breast cancer in their lifetime, and 1 in 100 women will develop ovarian cancer. Most women who get breast or ovarian cancer do not carry a BRCA mutation.

Women with a mutation in the BRCA gene are at increased risk for cancer of the breast and ovary. Women with a BRCA mutation have a 50 to 85 percent risk of developing breast cancer by approximately 70 years, and a 20 to 40 percent risk of ovarian cancer. Therefore, not all women who have inherited a BRCA mutation will develop breast or ovarian cancer, but the risks are much higher.

A woman who carries a BRCA mutation has an increased risk of developing another primary breast cancer in their breast.

A man who carries a BRCA mutation has a 1-7% lifetime risk of breast cancer, and his risk of prostate cancer is increased at least two-fold compared to other men, especially up to age 65-70 years.

The risk for pancreatic, bile duct, and melanoma cancers also appear to be slightly increased in individuals with a BRCA mutation.

How do I know if I have a genetic mutation?

If you have a strong family history, it may be appropriate for your General Practitioner to refer you to your local Genetic Service.

A strong family history may include:

Three or more close blood relatives on the same side of the family with breast or ovarian cancer

OR

Two or more close blood relatives on one side of the family (mother’s or father’s) with breast or ovarian cancer PLUS one or more of the following features:

  • breast and ovarian cancer in the same person
  • breast cancer before age 40
  • ovarian cancer before age 50
  • breast cancer in both breast
  • breast cancer in a male relative
  • Jewish ancestry

Any blood relative with a BRCA mutation

What will a referral to Genetic services involve?

The risk of developing breast or ovarian cancer, based on the family history, will be calculated and discussed in more detail. They can answer questions about the family history and discuss what surveillance and management may be appropriate. They will discuss the limitations, potential benefit, disadvantages and appropriateness of genetic testing, and may arrange testing for you or your family.

Searching for a BRCA mutation in a family is recommended to start in a family member with cancer to reduce the risk of false negative results and to increase the chance of finding a mutation. To date, more than 3000 different mutations have been identified, most unique to only a few families. Should a mutation be found, testing can be offered to other at-risk adult family members.

Genetic testing is only useful for a small proportion of people with breast cancer since at least 95% of breast cancer is not caused by a BRCA mutation.

What are the options for a person who has a positive test result?

Several options are available for managing cancer risk in individuals who have a harmful BRCA1 or BRCA2 mutation. There is good research follow-up data on the effectiveness of risk-reducing surgery in BRCA mutation carriers. New treatments which may be particularly effective in BRCA mutation carriers are also being trialled right now by dedicated researchers around the world.

Surveillance - survelillance means cancer screening, or a way of detecting the disease early. Screening does not, however, change the risk of developing cancer. The goal is to find cancer early, when it may be most treatable.

Surveillance methods for breast cancer may include mammography, magnetic resonance imaging (MRI) and clinical breast exams. With careful surveillance, many breast cancers will be diagnosed early enough to be successfully treated.

For serious ovarian cancer (the type of ovarian cancer typically associated with a BRCA mutation), surveillance with transvaginal blood tests for CA-125 antigen and clinical exams is available. Although there is limited success, surveillance can sometimes find ovarian cancer at an early stage, but it is uncertain whether these methods can help reduce a woman's chance of dying from this disease. Removal of the ovaries and fallopian tubes is generally recommended when a women has completed her family (not beyond the age of 40 years) and/or 5-10 years earlier than the youngest family member with a BRCA mutation who has ovarian cancer. At this stage, removal of the ovaries seems to be the only safe way to manage the risk of ovarian cancer in a BRCA mutation carrier.

Risk-reducing (Prophylactic) Surgery - This type of surgery involves removing as much of the "at-risk" tisssue as possible in order to significantly reduce the chance of developing cancer. Bilateral prophylactic mastectomy (removal of healthy breasts) and prophylactic salpingo-oophorectomy (removal of healthy fallopian tubes and ovaries) do not, however, offer a guarantee against developing cancer, because not all at-risk tissue can be removed by these procedures, but it does greatly reduce the odds. The risk of developing breast or ovarian cancer can be reduced by 90% or more with risk-reducing surgery.

Looking for more information? Try...

1) Genetic Health Services New Zealand. This nationwide service provides genetic diagnostic and counselling services from three main centres Auckland, Wellington and Christchurch. For patients referred to the service via their health professional their website provides a guide to what to expect at your appointment.

2) Your GP. Your GP is your recommend first point of contact. To make the most of your appointment it is recommended to take as much information as possible about your family history along with you.