A family history of ovarian cancer, such as a grandmother having had the disease, often prompts questions about personal risk. While this concern is understandable, it is important to recognize that most ovarian cancers develop sporadically, meaning they are not directly linked to an inherited genetic mutation. However, a proportion of ovarian cancers, estimated to be between 15% and 25%, are considered hereditary, stemming from specific gene changes passed down through generations.
Understanding Inherited Cancer Risk
Inherited cancer risk arises when a person is born with a mutation in a gene that normally helps protect against cancer. These mutations are present in every cell of the body from birth and can increase the likelihood of developing certain cancers over a lifetime. It is not the cancer itself that is inherited, but rather a predisposition to developing it. This means the individual has a higher chance of developing cancer compared to the general population.
These inherited genetic predispositions often follow an autosomal dominant inheritance pattern. Only one copy of the mutated gene, inherited from either parent, is sufficient to increase cancer risk. Therefore, even if a direct parent did not develop ovarian cancer, they could still carry and pass on a gene mutation received from a grandparent, thereby transmitting the increased risk. This pattern explains how a family history can skip generations or appear to affect only one side of a family.
Key Genes Associated with Ovarian Cancer
The genes most commonly linked to an increased risk of inherited ovarian cancer are BRCA1 and BRCA2. These genes are known as tumor suppressor genes, meaning they normally produce proteins that help repair damaged DNA and prevent cells from growing and dividing uncontrollably. When a person inherits a harmful mutation in either BRCA1 or BRCA2, this DNA repair mechanism can be impaired, leading to an accumulation of genetic errors that increase the likelihood of cancer development.
Women who inherit a harmful BRCA1 mutation face an estimated lifetime risk of ovarian cancer ranging from 35% to 70%. For those with a BRCA2 mutation, the lifetime risk is somewhat lower, typically between 10% and 30%. These figures represent a significant increase compared to the general population’s lifetime ovarian cancer risk, which is approximately 1% to 2%.
Beyond BRCA1 and BRCA2, other genes are also associated with an elevated ovarian cancer risk, though less frequently. These include genes involved in Lynch syndrome, such as MLH1, MSH2, MSH6, and PMS2. Lynch syndrome primarily increases the risk of colorectal and endometrial cancers, but it also confers a moderate increase in ovarian cancer risk, estimated to be around 1% to 12%. Mutations in genes like RAD51C, RAD51D, BRIP1, and PALB2 have also been identified as contributing to inherited ovarian cancer susceptibility.
Factors Influencing Your Individual Risk
An individual’s overall risk is influenced by a combination of genetic and non-genetic factors. Age is a significant determinant, with the risk of ovarian cancer generally increasing as women get older, particularly after menopause. Most ovarian cancers are diagnosed in women over the age of 50, with about half of cases found in women 63 years of age or older.
Reproductive history also plays a role in influencing ovarian cancer risk. Women who have never given birth or have had fewer full-term pregnancies may have a slightly higher risk. Conversely, factors like using oral contraceptives for several years have been shown to reduce ovarian cancer risk by as much as 26% to 50%. This protective effect can persist for many years after stopping the pill.
Other lifestyle and medical factors can contribute to an individual’s risk profile. Endometriosis, a condition where tissue similar to the lining of the uterus grows outside the uterus, is associated with a modestly increased risk of certain types of ovarian cancer, potentially up to four times higher for some subtypes. Obesity, defined as a body mass index (BMI) of 30 or higher, has also been linked to a slightly elevated risk, with a 6% to 30% increased risk for every 5-point increase in BMI. Additionally, a personal history of breast cancer can increase the risk of developing ovarian cancer, especially if the breast cancer was linked to a BRCA gene mutation.
What to Do if You Have a Family History
If you have a family history of ovarian cancer, particularly if your grandmother was affected, discussing this information with a healthcare provider is a crucial first step. Your doctor can evaluate your family pedigree, a detailed diagram of your family’s health history, to assess patterns of cancer and determine if genetic counseling is appropriate. This initial conversation helps to contextualize your grandmother’s diagnosis within your broader family health picture.
Genetic counseling is a specialized service where a trained professional, such as a genetic counselor, can provide a comprehensive risk assessment. During a session, the counselor will collect detailed family medical history, discuss the likelihood of an inherited cancer syndrome, and explain the benefits, limitations, and potential implications of genetic testing. They can help you understand complex genetic information in an accessible way, allowing for informed decision-making.
If indicated, genetic testing can be performed, typically using a blood or saliva sample, to look for specific mutations in genes like BRCA1, BRCA2, and others associated with ovarian cancer. A positive test result means an inherited mutation has been identified, indicating an increased lifetime risk of developing certain cancers. Conversely, a negative result suggests no known inherited mutation was found, though it does not eliminate all cancer risk, as most cancers are not hereditary.
Managing an Increased Ovarian Cancer Risk
For individuals identified as having an increased ovarian cancer risk, either through genetic testing or comprehensive risk assessment, several management strategies can be considered. Regular surveillance is an option, typically involving transvaginal ultrasound (TVUS) and CA-125 blood tests. CA-125 is a protein that can be elevated in some ovarian cancer cases, and TVUS can visualize the ovaries. However, these screening methods have not consistently shown effectiveness in detecting ovarian cancer early enough to improve survival rates in high-risk women.
Risk-reducing surgery is often considered the most effective strategy for significantly lowering ovarian cancer risk in women with inherited BRCA1 or BRCA2 mutations. This procedure, known as a prophylactic bilateral salpingo-oophorectomy (removal of both ovaries and fallopian tubes), can reduce ovarian cancer risk by approximately 80% to 96% in BRCA mutation carriers. This surgery is typically recommended after childbearing is complete, often between the ages of 35 and 40 for BRCA1 carriers and 40 and 45 for BRCA2 carriers.
Another less common strategy is chemoprevention, which involves using medications to reduce cancer risk. Oral contraceptives, for example, have been shown to decrease ovarian cancer risk in the general population and may be considered for risk reduction in certain high-risk individuals. The decision to pursue any risk management strategy requires a thorough discussion with healthcare providers, weighing individual risk factors, potential benefits, and associated side effects or implications.