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Ovarian cancer is a classification of several different types and subtypes of cancer that are found in the ovaries, some of which are considered hereditary. Though anyone with ovaries can develop ovarian cancer, there are certain risk factors that can make getting the disease more likely. One of the biggest known risk factors for ovarian cancer is the presence of specific genetic mutations that can be passed down from a mother or father.
While only about 5 – 10% of all cancers are linked to known inherited gene mutations, it is estimated that up to 25% of ovarian cancers are hereditary. Researchers are continuing to uncover additional genetic variations that may increase a person’s risk of developing the disease. Knowing if you have ovarian cancer genetic markers is important, because there are preventative options, such as a risk-reducing salpingooophorectomy, available for those whose genetic mutations put them at high risk for ovarian cancer.
How do gene mutations cause cancer?
Genetic mutations can cause cancer by issuing faulty instructions for cells, resulting in abnormal, malignant cells that can grow, multiply and spread.
In order to understand how genetic mutations (also called genetic alterations) sometimes lead to cancer, it’s helpful to have a basic understanding of the relationship between chromosomes, genes and DNA, and how they control the function of cells.
Every person is made up of trillions of cells. Each type of cell works to create and maintain specific parts of the body, but they all contain, at their core, the same basic set of instructions. The instructions live inside every cell’s nucleus, on 23 pairs of chromosomes — one chromosome from each pair is inherited from the biological mother, and the other is from the biological father. Chromosomes are made up of DNA — long double-helix strands of chemical bases that serve as “code” making proteins in cells of the body. Individual sections of DNA strands associated with instructions for a particular protein are called genes.
Cells rely on proteins to transmit signals that regulate cell growth, division, and function. Sometimes genetic mutations can result in protein structure that impair a cell’s ability to grow or divide or function normally. Uncontrolled growth of abnormal cells may develop into a cancer. Genetic mutations may be inherited (germline), and present in all cells of the body, or acquired (somatic), specifically in tumor cells. Both inherited and acquired gene mutations have been associated with cancer.
BRCA1 and BRCA2 Genes
Mutations in BRCA1 or BRCA2 genes account for the majority of hereditary ovarian cancers, as well as 10% – 15% of all ovarian cancer diagnoses. An inherited BRCA mutation is sometimes referred to as hereditary breast and ovarian cancer syndrome (HBOC). A BRCA mutation can be inherited from a person’s mother or father.
BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2) are responsible for producing proteins that are meant to repair damaged DNA. These types of genes are sometimes referred to as “tumor suppressor” genes, because when they function well, they can repair damaged DNA and keep abnormal cell growth in check. When they are damaged, as with BRCA1 and BRCA2 mutations, they are unable to repair damaged DNA, which can lead to errors in proteins and possibly cancer.
In the general population, about 1.3% of women will develop ovarian cancer, but the risk is much higher for those with a harmful BRCA mutation. The lifetime risk for women with a BRCA1 mutation to develop ovarian cancer is an estimated 35% to 70%. The lifetime risk for women with a BRCA2 mutation to develop ovarian cancer by age 70 is an estimated 10% to 30%. Those with BRCA mutations are also significantly more likely to develop breast cancer, and are more likely to develop breast or ovarian cancer at a younger age than those without BRCA mutations.
Though BRCA mutations are most often associated with women’s increased risk for breast and ovarian cancer, men are also at an elevated risk for developing male breast cancer, and transgender men are at risk as well. People with BRCA mutations are also more likely to develop some other cancers, such as prostate cancer, pancreatic cancer, and melanoma.
Women who carry a change in one of these genes have up to a 60% lifetime risk of developing ovarian cancer and up to an 85% lifetime risk of developing breast cancer. These cancers can also occur at ages much earlier than seen in the general population with some breast cancers being seen as early as the mid-20’s.
Other Genetic Cancer Syndromes
Although the most common hereditary syndrome associated with ovarian cancer cases is linked with mutations in the BRCA1 or BRCA2 gene, there are other inherited gene mutations that may increase the risk of ovarian cancer.
Lynch syndrome is a genetic mutation known to increase the risk of several types of cancer, including ovarian cancer. About 10% – 15% of hereditary ovarian cancers are caused by Lynch syndrome. Because Lynch syndrome was initially associate with an increase risk of colon cancer, it is also known as hereditary non-polyposis colorectal cancer, or HNPCC.
There are several gene mutations that fall under the umbrella of Lynch syndrome. Scientists have identified variations in the MLH1, MSH2, and MSH6 genes as important risk factors for ovarian cancer.
Lynch syndrome can be passed down from a mother or father, and affects what are called “mismatch repair genes,” the genes in charge of finding and fixing copy errors that reside in the DNA of new cells. In a person with Lynch syndrome, DNA errors in cells may not get fixed, which may result in the production of defective proteins, uncontrolled cell growth, and eventually cancer.
If either parent has Lynch syndrome, their child will have a 50% chance of inheriting the condition as well. Women who have Lynch Syndrome have 9-12% lifetime risk of developing ovarian cancer. Women with changes in these genes also have up to a 60% lifetime risk of uterine or colon cancer. Similar to BRCA1 and BRCA2, changes in these genes can cause very early onset cancers, with some of the cancers occurring as early as age 25.
While some of the cancers associated with changes in these genes only occur in women, men with changes in these genes can also be at increased risk of developing certain cancers. For this reason, men whose family history meets any of the increased risk criteria outlined previously are encouraged to talk with their doctors.
Other gene mutations linked with ovarian cancer
Researchers are continuing to investigate genetic mutations, both inherited and acquired, that may increased the risk of cancer. Studies are emerging that link ovarian cancer with mutations in other genes involved in DNA repair, including:
- RAD51C and RAD51D, and BRIP1
- PALB2, which stands for Partner and Localizer of BRCA2
- STK11, resulting in a condition called Peutz-Jeghers syndrome (PSJ), a rare genetic syndrome that can cause also cause polyps to develop in the stomach and intestine
- ATM, associated with an estimated 2-3% lifetime risk of ovarian cancer
There is no reliable screening test for ovarian cancer, which makes awareness of genetic risk factors one of the most important tools for preventing ovarian cancer. Genetic testing can help identify inherited mutations known to increase the chances of getting the disease — and genetic testing will not only help the person being tested, but their children and families as well, by giving them information about their increased genetic risk, and allowing them to take precautionary steps if needed.
Genetic testing is a process in which a blood test may help to determine if you or your family members are at increased risk of ovarian or other cancers. The blood test looks to see if you are carrying a gene change passed down to you by one of your parents that is associated with increased cancer risk.
Those whose personal or family history meets any of the criteria below may wish to consider genetic testing:
- First-degree relatives (parent, sibling, child,) who have any cancer, or people with several relatives on one side of the family with one type of cancer
- Members of the family who have cancers that are associated with genetic mutations, such as ovarian, breast, colon, or pancreatic cancers
- A family member with more than one type of cancer
- Any family members who had cancer at a young age, had more than one type of cancer, or had rare hereditary cancer syndromes
- Ashkenazi Jewish ancestry, that is associated with high risk of BRCA mutations
- Confirmation of genetic mutations in family members who have undergone genetic testing
- Existing cancer diagnosis that show signs of possibly being linked to hereditary genetic mutations
Cascade testing, sometimes called cascade screening, is a process for genetic testing that can help identify hereditary conditions within a family. Often, cascade testing starts with one person’s cancer diagnosis. If doctors find that their cancer is related to a harmful mutation, close family members can then be tested for that same mutation. If more family members are identified as being at risk, this process can be repeated for their own close relatives. Cascade testing can be an extraordinarily important tool for identifying those at elevated risk, so preventative or risk-reduction measures can be offered. Cascade testing is often, though not always, covered by insurance.
Biomarker testing is an overarching term that encompasses genetic testing as well as testing for other biological factors that may affect cancer risk. Biomarker testing may analyze a patient’s blood or tissue for tumor markers and mutations, or for non-hereditary markers like a tumor’s protein expression. The information gleaned from biomarkers may provide information about risk stratification, and may also help determine the most effective treatment plan for a cancer patient.
Genetic counseling is a process during which a genetic counselor or other appropriate medical professional will ask a series of questions about you and your family’s cancer history as well as your heritage. This information will be used to assist the genetic counselor in determining if you may be at increased risk of ovarian and related cancers. If you have a personal or family history of cancer, undergoing genetic counseling can be helpful and informative in choosing whether to pursue genetic testing.
You can find a genetic counselor through the National Society of Genetic Counselors.
How OCRA can help
OCRA strongly believes in the importance of genetic testing as a risk reduction measure for ovarian cancer. If you have concerns that you may have an inherited predisposition to developing the disease, OCRA can help.
- OCRA’s patient support line is open at 212-268-1002, to answer questions about genetic testing and counseling, and help guide you toward next steps.