Ovarian Cancer Series 03: How Much Does a BRCA Gene Mutation Increase Ovarian Cancer Risk?

 

If someone in your family has been diagnosed with ovarian or breast cancer, or if genetic testing has identified a BRCA gene change, one question may immediately come to mind:

“If I have a BRCA mutation, does that mean I will develop ovarian cancer?”

Certain inherited harmful changes in BRCA1 and BRCA2—more precisely called pathogenic variants—can substantially increase the risk of ovarian cancer. However, having a BRCA pathogenic variant does not mean that ovarian cancer will definitely develop.

What matters is understanding how much the risk increases, how family history should be interpreted, and what a genetic test result may mean for you and your family.

What Are BRCA1 and BRCA2?

BRCA1 and BRCA2 are sometimes referred to as “breast cancer genes” or even “cancer genes,” but their normal function is not to cause cancer.

Both genes produce proteins that help repair damaged DNA and play an important role in protecting cells from becoming cancerous.

Everyone normally has two copies of each BRCA gene, one inherited from each parent. A person who inherits a pathogenic variant in one copy generally still has another normal copy. If additional genetic changes cause that normal copy to stop functioning in a cell, the normal DNA-repair pathway can be compromised, making it easier for further changes associated with cancer development to accumulate.

BRCA pathogenic variants can be inherited from either the mother or the father, and both women and men can carry them. A person who inherits a BRCA pathogenic variant can also pass it on to their children.

For this reason, BRCA-related hereditary cancer risk should not be considered only a women’s issue, nor should family history be evaluated only on the mother’s side.

How Much Does a BRCA Variant Increase Ovarian Cancer Risk?

BRCA pathogenic variants are important because the difference in ovarian cancer risk compared with the general population is substantial.

According to the U.S. National Cancer Institute (NCI), the lifetime risk of ovarian cancer among women in the general population is approximately 1.1%.

The risk is considerably higher among women who inherit a harmful BRCA1 or BRCA2 variant.

Group	Lifetime Risk of Ovarian Cancer
Women in the general population	About 1.1%
BRCA1 pathogenic variant	About 39–58%
BRCA2 pathogenic variant	About 13–29%

In these estimates, ovarian cancer includes fallopian tube cancer and primary peritoneal cancer.

Another important point is that BRCA1 and BRCA2 do not carry the same level of ovarian cancer risk.

In general, women with an inherited BRCA1 pathogenic variant have a higher lifetime ovarian cancer risk than women with an inherited BRCA2 pathogenic variant.

For this reason, simply saying that someone is “BRCA-positive” does not fully describe that person’s risk. The specific gene involved, age, personal cancer history, and family history all need to be considered.

Does a BRCA Pathogenic Variant Mean You Will Develop Ovarian Cancer?

No.

Having an increased genetic risk and actually developing cancer are not the same thing.

For example, a lifetime ovarian cancer risk of approximately 39–58% among women with an inherited BRCA1 pathogenic variant does not mean that every woman with that variant will develop ovarian cancer.

Even people who carry the same disease-associated variant do not all develop the associated disease. In genetics, this is known as incomplete penetrance.

A BRCA pathogenic variant should therefore be understood not as a diagnosis predicting future cancer, but as important information indicating that the probability of developing certain cancers is higher than it is in the general population.

The purpose of identifying hereditary risk is not to predict with certainty whether cancer will occur. It is to understand an individual’s level of risk and make informed decisions about appropriate counseling and risk management.

If Ovarian Cancer Runs in My Family, Should I Have BRCA Testing?

A personal or family history of ovarian cancer and certain other cancers can provide important clues when evaluating hereditary cancer risk.

Genetic risk assessment may be particularly important when ovarian cancer has occurred in the family, breast cancer has occurred at a relatively young age, related cancers have appeared in multiple family members, or an uncommon cancer such as male breast cancer has occurred. A family history of pancreatic cancer or certain prostate cancers may also be relevant when assessing BRCA-related risk.

It is particularly important to know whether a BRCA1 or BRCA2 pathogenic variant has already been identified in the family.

Family history on both the maternal and paternal sides of the family matters.

Because BRCA pathogenic variants can be inherited from either parent, hereditary cancer risk assessment may consider which cancers occurred in close blood relatives and the ages at which they were diagnosed.

However, having a family history of cancer does not automatically mean that a BRCA pathogenic variant is present. Likewise, the absence of an obvious family history does not completely rule out hereditary risk.

The decision to undergo genetic testing therefore should not depend solely on whether someone has a relative with cancer. Personal cancer history, the types of cancer occurring in the family, ages at diagnosis, maternal and paternal family histories, and any previously identified pathogenic variants should all be considered together.

When possible, genetic testing for a suspected hereditary cancer syndrome may begin with a family member who has had cancer because that can make the results more informative for other relatives.

Are Other Genes Besides BRCA Associated With Ovarian Cancer?

BRCA1 and BRCA2 are the best-known hereditary ovarian cancer genes, but they are not the only genes associated with increased ovarian cancer risk.

Pathogenic variants in genes such as BRIP1, RAD51C, and RAD51D have also been associated with increased ovarian cancer risk.

Another important hereditary cancer condition is Lynch syndrome.

Lynch syndrome is associated with pathogenic variants affecting the DNA mismatch-repair pathway. Genes involved include MLH1, MSH2, MSH6, PMS2, and EPCAM.

Lynch syndrome is particularly well known for increasing the risks of colorectal and endometrial cancers, but it is also associated with increased ovarian cancer risk. The degree of risk can vary depending on which gene is involved.

For this reason, evaluating hereditary ovarian cancer risk does not always mean testing only BRCA1 and BRCA2. Depending on a person’s personal and family cancer history, testing several cancer-related genes together through a multigene panel may be considered.

Why Is Genetic Counseling Important Before and After Testing?

Genetic testing can often be performed using a blood or saliva sample, but the results are not always as simple as “positive” or “negative.”

First, it matters which genes were tested and how comprehensive the test was.

If a specific pathogenic variant has already been identified in the family, testing whether another family member carries that same variant can provide relatively clear information.

The meaning of a negative result can be different when no disease-causing variant has previously been identified in the family.

Genetic testing may also identify a variant of uncertain significance, or VUS.

A VUS means that a genetic change has been found, but current evidence is not sufficient to determine whether that change increases cancer risk or represents a harmless genetic variation.

For this reason, a VUS should not be interpreted in the same way as a pathogenic variant, and a VUS alone should not be used to conclude that cancer risk is increased or to make risk-reducing medical or surgical decisions.

The classification of a VUS can change as more scientific evidence becomes available. Personal cancer history, family history, and other risk factors therefore remain important when interpreting this type of result.

This is why professional genetic counseling can be valuable both before testing and after the results are available.

Does a Negative Genetic Test Mean There Is No Ovarian Cancer Risk?

Not necessarily.

If a specific BRCA pathogenic variant has already been identified in a family and testing shows that you did not inherit that particular variant, the result can usually be interpreted more clearly.

The situation is different when no underlying pathogenic variant has previously been identified in the family.

There may be hereditary factors that were not detected by the test, and ovarian cancer also has risk factors unrelated to BRCA. Therefore, “negative” does not automatically mean “no ovarian cancer risk.”

The type and scope of genetic testing also matter.

Some direct-to-consumer genetic tests examine only selected variants rather than comprehensively testing BRCA1 and BRCA2.

A negative result from a limited test therefore should not be interpreted as proof that no pathogenic BRCA1 or BRCA2 variant is present.

If personal or family cancer history suggests hereditary cancer risk, it is important to discuss the scope of the test and whether additional evaluation may be appropriate with a healthcare professional or genetic counselor.

What Happens If a BRCA Pathogenic Variant Is Found?

If a BRCA pathogenic variant is identified, the next step is to understand what the result means for your individual risk and future risk management.

Not everyone with a BRCA pathogenic variant is in the same situation.

Future decisions may depend on whether BRCA1 or BRCA2 is involved, your age, which cancers have occurred in your family and at what ages, and whether you have a personal history of cancer.

An inherited pathogenic variant may also have implications for blood relatives. When appropriate, relatives may be offered testing for the same familial variant, a process known as cascade testing.

For this reason, identifying a pathogenic variant is usually followed by discussion with healthcare professionals and genetics specialists about individual risk and appropriate management.

Specific strategies for reducing ovarian cancer risk, including options that may be considered for people at high hereditary risk, will be discussed in the next article, “Can Ovarian Cancer Be Prevented? Ways to Reduce Risk.”

Final Takeaway

Pathogenic variants in BRCA1 and BRCA2 can substantially increase ovarian cancer risk. Compared with a lifetime risk of about 1.1% among women in the general population, the estimated lifetime risk is approximately 39–58% for women with an inherited BRCA1 pathogenic variant and 13–29% for women with an inherited BRCA2 pathogenic variant.

However, having a BRCA pathogenic variant is not the same as having ovarian cancer. BRCA1 and BRCA2 are also not the only genes associated with hereditary ovarian cancer risk.

Genetic test results need to be interpreted in context. Personal cancer history, cancer patterns and ages at diagnosis in the family, maternal and paternal family histories, the specific genes tested, and the scope of testing can all affect what a result means.

The purpose of genetic testing is not to predict with certainty whether cancer will develop. It is to better understand individual risk and make informed decisions about appropriate risk management. When hereditary ovarian cancer risk is suspected or a pathogenic variant is identified, professional genetic counseling can help clarify what the result means for both the individual and their family.

References

National Cancer Institute. BRCA Gene Changes: Cancer Risk and Genetic Testing Fact Sheet.
https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet

National Cancer Institute. Genetic Testing Fact Sheet.
https://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet

National Cancer Institute. Genetics of Breast and Gynecologic Cancers (PDQ®)–Health Professional Version.
https://www.cancer.gov/types/breast/hp/breast-ovarian-genetics-pdq

American College of Obstetricians and Gynecologists. Hereditary Cancer Syndromes and Risk Assessment. Committee Opinion No. 793.
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2019/12/hereditary-cancer-syndromes-and-risk-assessment

National Cancer Institute. Genetics of Colorectal Cancer (PDQ®)–Health Professional Version.
https://www.cancer.gov/types/colorectal/hp/colorectal-genetics-pdq