What are genes?

Genes carry small individual collections of information within each cell of the human body. Each gene is made of a unique sequence of DNA. Researchers working on the Human Genome Project have estimated that there are as many as 30,000 different genes in each cell. Genes are packaged onto chromosomes. There are 23 pairs of chromosomes in each cell. One chromosome of each pair is inherited from the person's father and one from the person's mother.

Genes control how a cell functions, including how quickly it grows, how often it divides, and how long it lives. To control these functions, genes produce proteins that perform specific tasks and act as messengers for the cell. Therefore, it is essential that each gene have the correct instructions or "code" for making its protein so that the protein can perform the proper function for the cell.

What role do genes play in ovarian cancer?

Cancer begins when one or more genes in a cell are mutated (changed), creating an abnormal protein or no protein at all. The information provided by an abnormal protein is different from that of a normal protein, which can cause cells to multiply uncontrollably and become cancerous.

A person may either be born with the genetic mutation in all of their cells (germline mutation) or acquire a genetic mutation in a single cell during his or her lifetime. An acquired mutation is passed on to all cells that develop from that single cell (called a somatic mutation). Somatic mutations can sometimes be caused by environmental factors, such as cigarette smoke. Most ovarian cancers (about 85% to 90%) are considered sporadic, meaning that the damage to the genes occurs by chance after a person is born. Inherited ovarian cancers are less common (about 10% to 15%) and occur when gene mutations are passed within a family, from one generation to the next.

What are the chances a mutated gene is inherited?

Every cell usually has two copies of each gene: one inherited from the mother and one inherited from the father. Most types of hereditary ovarian cancer follow an autosomal dominant inheritance pattern, in which a mutation needs to happen in only one copy of the gene for the person to have an increased risk of getting the disease. This means that a parent with a gene mutation may pass on a copy of the normal gene or a copy of the gene with a mutation. Therefore, a child who has a parent with a mutation has a 50% chance of inheriting that mutation. A brother, sister, or parent of a person who has a gene mutation also has a 50% chance of having the same mutation.

What is a woman's average risk for ovarian cancer?

A woman's average risk of developing ovarian cancer during her lifetime is about one in 71.

How common is ovarian cancer?

Ovarian cancer is the eighth most common cancer and fifth most common cause of cancer death among women. In 2008, an estimated 21,650 women in the United States will be diagnosed with ovarian cancer. It is estimated that 15,520 deaths from this disease will occur this year. Ovarian cancer accounts for nearly 3% of all cancers among women.

How can a woman know if she has inherited a genetic mutation that increases her risk of ovarian cancer?

Only genetic testing can determine whether a person has a genetic mutation. Most experts strongly recommend that people considering genetic testing first consult a genetic counselor. Genetic counselors are trained to explain the risks and benefits of genetic testing.

For more information, read Genetic Testing and What to Expect When Meeting With a Genetic Counselor.

How does a woman know if ovarian cancer runs in her family?

Ovarian cancer may run in the family if first-degree relatives (mother, sisters, daughters) or many other family members (grandmothers, aunts, nieces, granddaughters) have had ovarian cancer.

What is a woman's risk if ovarian cancer runs in her family?

If a woman's first-degree relatives developed ovarian cancer, her risk of ovarian cancer is about 3 times as high as the average woman's risk of ovarian cancer. The risk increases if other close relatives have had ovarian cancer.

Which inherited genetic mutations raise the risk of ovarian cancer?

There are several genes linked to an increased risk of ovarian cancer. Some of the most common hereditary cancer syndromes associated with ovarian cancer risk are described below.

Hereditary breast and ovarian cancer (HBOC) syndrome. Two genes are associated with HBOC, BRCA1 and BRCA2 (BRCA stands for BReast CAncer). Women who inherit a BRCA mutation have a 15% to 40% chance of developing ovarian cancer and a 50% to 85% chance of developing breast cancer. Both women and men with BRCA2 mutations may have an increased risk of breast cancer or other types of cancer. Approximately one in 40 women with Ashkenazi Jewish heritage carry a mutation in BRCA1 or BRCA2 genes that increases their risk of ovarian and breast cancer.

BRCA1 and BRCA2 are called tumor suppressor genes. A tumor suppressor gene makes proteins that prevent tumor formation by limiting cell growth. Mutations in a tumor suppressor gene cause a loss of the ability to restrict tumor growth and, as a result, cancer can develop. Genetic testing for the BRCA1 and BRCA2 genes is available.

For more information, read the Cancer.Net Guide to Hereditary Breast and Ovarian Cancer.

Hereditary non-polyposis colorectal cancer (HNPCC). Women with HNPCC (sometimes called Lynch syndrome) have about a 9% to 12% risk of developing ovarian cancer. The risk of uterine cancer in women with HNPCC is 20% to 50%. HNPCC is most commonly associated with an increased risk of colorectal cancer. The risk of colorectal cancer in families with HNPCC is 80%, which is several times greater than the average risk. People with HNPCC also have an increased risk of cancers of the stomach and small intestine. There may be some increased risk of breast cancer in families with HNPCC.

Mutations in the MLH1, MSH2, MSH6, and PMS2 genes are the most frequent cause of HNPCC. The genes associated with HNPCC are mismatch repair genes. A mismatch repair gene makes proteins that repair DNA mistakes that occur as a cell divides. If one of these genes has a mutation, the mistakes cannot be repaired, leading to damaged DNA and an increased risk of cancer.

Although multiple genes have been linked to HNPCC, most families with HNPCC have a mutation in only one of the genes. Genetic testing is available for the MLH1, MSH2, and MSH6 genes. The PMS2 gene is only tested as part of a clinical trial.

Women at risk for HNPCC may benefit from additional screening for ovarian and uterine cancers. Anyone at risk for HNPCC is encouraged to have increased screening for colorectal cancer.

For more information, read the Cancer.Net Guide to Hereditary Non-Polyposis Colorectal Cancer.

Peutz-Jeghers syndrome (PJS). Women with PJS have about a 20% risk of developing ovarian cancer. People with PJS often have multiple hamartomatous polyps, which are normal-appearing growths in the digestive tract that become a noncancerous tumor. These polyps cause an increased risk of colorectal cancer. People with PJS also have increased pigmentation (dark spots on the skin) on the face and hands. The increased pigmentation often appears in childhood and fades over time. Families with PJS also have an increased risk of breast, uterine, and lung cancers. The gene associated with PJS is called STK11. The STK11 is a tumor suppressor gene, and genetic testing is available.

For more information, read the Cancer.Net Guide to Peutz-Jeghers Syndrome.

Nevoid basal cell carcinoma syndrome (NBCCS). Women with NBCCS (also known as Gorlin syndrome) have an increased risk of developing fibromas (benign fibrous tumors) of the ovaries. There is a small risk that these fibromas could develop into a type of ovarian cancer called a fibrosarcoma. People with NBCCS often have multiple basal cell carcinomas, jaw cysts, and small skin pits on the palms of the hands and the bottom of the feet. People with NBCCS may also have medulloblastoma (a type of brain tumor) in childhood, macrocephaly (larger than average head size), unique facial features, and skeletal changes in the ribs and backbone. Although NBCCS is inherited in an autosomal dominant pattern, about 30% of people with NBCCS have no family history of the condition. The gene associated with NBCCS is called PTCH, and genetic testing is available.

For more information, read the Cancer.Net Guide to Nevoid Basal Cell Carcinoma Syndrome.

Are there other genetic conditions associated with an increased risk of ovarian cancer?

Other genetic conditions that are associated with a small increased risk of ovarian cancer include Li-Fraumeni syndrome and ataxia-telangiectasia.

Li-Fraumeni syndrome. People with LFS have up to a 50% chance of developing cancer by age 40 and a 90% chance of developing cancer by age 60. Some of the cancers most commonly associated with LFS are osteosarcoma (a type of bone cancer), soft tissue sarcoma, leukemia, breast cancer, brain cancer, and adrenal cortical tumors. An adrenal cortical tumor begins in the adrenal cortex, which is the outer layer of the adrenal glands. The adrenal glands are located on top of each kidney and are a part of the body’s endocrine (hormonal) system.

LFS is a rare condition. The gene associated with LFS, called p53, is a tumor suppressor gene. Testing for p53 gene mutations is available for families who may have LFS. Another gene, CHEK2, may cause LFS for some families. Testing for mutations in the CHEK2 gene is only available as part of a research study.

For more information, read the Cancer.Net Guide to Li-Fraumeni syndrome.

Ataxia-telangiectasia. Ataxia-telangiectasia (A-T) is a rare recessive disorder characterized by progressive neurological problems that lead to difficulty walking. Signs of A-T develop in childhood. Children may begin staggering and appear unsteady shortly after learning to walk. Most people with A-T will eventually need to use a wheelchair. Slurred speech and difficulty with writing and other tasks develop over time. Red marks that are caused by dilated capillaries (tiny blood vessels), called telangiectases, often appear on the skin and eyes. People with A-T also have a weakened immune system and are prone to infections.

There is about a 40% risk of cancer for people with A-T. The most common cancers associated with A-T are leukemia and lymphoma. As individuals with A-T live longer, other types of cancer, including melanoma, sarcoma, and breast, ovarian, and stomach cancers, are being reported in adults. However, it is too early to determine if there is truly an increased risk for these cancers that is caused by A-T, or whether these are sporadic cancers developing in adults who also happen to have A-T.

A-T is inherited as an autosomal recessive condition. In autosomal recessive inheritance, a person needs to have two copies of a gene mutation in order to have the disease. This means that each parent must have one mutated gene and one normal gene. If both parents carry a gene mutation for A-T, each of their children will have a 25% chance of inheriting both gene mutations and having A-T. The gene associated with AT is called ATM. For people who have one altered copy of the gene, there may be a somewhat increased risk of melanoma and breast, ovarian, and stomach cancers. Genetic testing for the ATM gene is available.

For more information, read the Cancer.Net Guide to Ataxia-Telangiectasia.

What is a person's risk level?

In addition to family history, other environmental and lifestyle factors may increase the risk of ovarian cancer. Discussing family history and personal risk factors with a doctor can help a person better understand his or her risk. People with a higher than average risk may benefit from genetic counseling and early detection strategies. Some women opt to have a prophylactic oophorectomy (the removal of healthy ovaries), which reduces the risk of both breast and ovarian cancers. Prophylactic surgery does not, however, completely eliminate the risk of either breast or ovarian cancer.

A risk factor is anything that increases a person's risk of developing cancer. Having a particular genetic mutation linked to ovarian cancer cannot predict that a person will develop cancer. Controllable risk factors, such as eating a balanced diet, maintaining a healthy weight, exercising, limiting alcoholic beverages, and avoiding tobacco products also play a role. Most women who develop ovarian cancer have few known risk factors. Research to better understand the link between genetic mutations and ovarian cancer is ongoing. Talk with a doctor for more information about risk factors, prevention, and screening for ovarian cancer.

More Information

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Cancer.Net Guide to Ovarian Cancer

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