Uterine and ovarian hereditary cancer syndromes

Slindokuhle Sibiya describes the hereditary cancer syndromes that increase the risk of uterine and ovarian cancer.

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Cancer happens when cells in the body grow and divide in an uncontrolled way. There are many different types of cancer, usually named according to where they start.

Uterine and ovarian cancers affect the female reproductive system. Uterine cancer (also called endometrial cancer) starts in the lining of the uterus, while ovarian cancer begins in the ovaries.

Most cancers (about 85%) happen by chance. But in some cases, a person is born with changes in certain genes that increase their risk of developing cancer. These are known as hereditary cancer syndromes, and some can increase the risk for uterine or ovarian cancer.

While it can be frightening to know you’re at a higher risk, learning about hereditary cancer syndromes can help you and your family take control of your health. Genetic testing, personalised screening, and preventive options can all support early detection and even prevention of cancer.

Uterine and ovarian hereditary cancer syndromes

Hereditary cancer syndromes are caused by inherited variants (mutations) in genes that usually protect the body from cancer. These genetic changes can be passed from parent to child and may significantly increase the lifetime risk of developing certain cancers.

The two most common inherited conditions that increase the risk of ovarian cancer are Lynch syndrome and hereditary breast and ovarian cancer (HBOC) syndrome. Some people may also carry mutations in other genes, such as BRIP1, RAD51C, and RAD51D, which aren’t part of a defined syndrome but still raise the risk for ovarian cancer. BRIP1 variants increase the lifetime ovarian cancer risk by around 5–15%, while RAD51C and RAD51D increase the risk by 10–20%.

Lynch syndrome also increases the risk for uterine cancer. Other less common hereditary syndromes like Cowden syndrome (caused by changes in the PTEN gene) and Peutz-Jeghers syndrome (caused by changes in STK11) can increase the risk of uterine cancer as well.

In the general population, the lifetime risk of ovarian cancer is about 1–2%, and for uterine (endometrial) cancer, it’s around 3%. But for individuals with mutations in certain genes, these risks can be much higher. The risk figures provided are based on the 2025 National Comprehensive

Cancer Network (NCCN) Guidelines:

BRCA1: Ovarian cancer risk of 39–58%.

BRCA2: Ovarian cancer risk of 13–29%.

Lynch syndrome: Uterine cancer risk up to 60%; ovarian cancer risk 1–38% (depending on the specific gene).

Cowden syndrome: Uterine cancer risk of around 28%, along with increased risks for breast, thyroid, kidney cancer, and melanoma.

Peutz-Jeghers syndrome: Uterine cancer risk of around 9–10%.

These mutations also increase the risk for other cancers, so identifying them is important not only for managing uterine or ovarian cancer risk but for overall health planning.

Genetic testing

Because these conditions are inherited, a person’s family history is one of the most important clues.

A history of breast, ovarian, uterine, or colon cancer, especially when diagnosed before age 50, may suggest the presence of a hereditary cancer syndrome.

Genetic testing can confirm whether someone has an inherited cancer risk. This information can help guide medical decisions for both the individual and their family members. First-degree relatives (parents, siblings, or children) have a 50% chance of carrying the same mutation, so testing can be life-saving for others in the family.

If you’re found to have a hereditary cancer syndrome, there are several steps you can take:

Screening: While there’s no proven method that reliably detects ovarian cancer early, you may be monitored with regular pelvic exams, ultrasounds, and CA-125 blood tests. For uterine cancer, yearly endometrial biopsies may be recommended starting in your 30s.

Preventive surgery: Some may choose risk-reducing surgery, such as removal of the uterus (hysterectomy) and/or the ovaries and fallopian tubes (salpingo-oophorectomy), once childbearing is complete. This can significantly lower cancer risk and reassure individuals.

Surveillance for other cancers: People with hereditary cancer syndromes may also need additional monitoring for related cancers, like breast or colon cancer.

Every care plan should be tailored to the individual, based on their personal and family history, specific genetic variant, and life circumstances. This is where genetic counselling plays a key role.

Genetic counselling

Genetic counsellors are healthcare professionals trained to guide individuals and families through the genetic testing process. They help assess cancer risk, explain test results, and discuss what they mean for medical care and family planning. They also provide emotional support and help patients make informed decisions that align with their values and goals.

A hereditary cancer syndrome doesn’t just affect you; it affects the whole family. Through genetic testing, personalised care, and family communication, people at risk can take meaningful steps to protect their health and empower those they love to do the same.

MEET THE EXPERT

Slindokuhle Sibiya is a first-year genetic counselling intern at the National Health Laboratory Service. As part of her training, she provides counselling in prenatal, paediatric, and cancer clinics across public hospitals.

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