Is Endometrial Cancer Inherited? Genetic Risk You Should Know

Most endometrial cancer isn’t inherited. The large majority of cases are sporadic, meaning they arise from factors built up over a lifetime rather than from a gene passed down through a family. 

A small proportion is different. Lynch syndrome, an inherited condition that may also increase the risk of bowel cancer, accounts for a minority of cases but changes what’s recommended, both for the person diagnosed and for their relatives. Here’s how genetics plays a part in endometrial cancer, which inherited conditions raise the risk, and when genetic testing may be appropriate.

What is endometrial cancer?

Endometrial cancer is a type of gynaecological cancer that develops in the endometrium, the inner lining of the uterus (womb). It is one of the most common gynaecological cancers and typically occurs after menopause, although it can also affect younger women.

Although this cancer is often referred to as uterus or uterine cancer, the two terms are not exactly the same. Uterus cancer is a broader term that describes cancers originating in the uterus, including endometrial cancer and the much rarer uterine sarcoma, which develops in the muscle or supporting tissues of the uterus.

Is endometrial cancer inherited?

Most cases of endometrial cancer occur sporadically, meaning they develop without being passed down through families. However, a small proportion are linked to inherited genetic mutations passed down from a parent. Because our bodies rely on certain genes to repair DNA and regulate cell growth, inheriting a damaged gene means abnormal cells can grow and multiply uncontrollably, which increases the risk of cancer.

What inherited conditions are linked to endometrial cancer?

Some of the inherited conditions associated with an increased risk of endometrial cancer include:

Lynch syndrome

Lynch syndrome, also known as the hereditary non-polyposis colorectal cancer (HNPCC) syndrome, is the most common inherited condition linked to endometrial cancer. Lynch syndrome is an inherited condition, meaning that each child of an affected parent has a chance of inheriting the altered gene.

When these genes mutate, they lose their ability to effectively repair DNA. As genetic damage accumulates over time, it significantly increases the likelihood of abnormal cells developing into cancer, particularly endometrial and ovarian cancers. Furthermore, women with Lynch syndrome tend to develop these cancers at a much younger age than the general population.

Cowden syndrome

Cowden syndrome is a rare inherited condition caused by changes in the PTEN gene. The PTEN gene usually works as a brake to control cell growth and stop abnormal cells from multiplying.

When the PTEN gene is altered, the brakes fail, and cells can grow out of control. This often leads to the development of non-cancerous (benign) clusters of normal tissue that grow in disorganised ways called hamartomas. 

Although less common than Lynch syndrome, people with Cowden syndrome have a higher lifetime risk of developing several cancers, including endometrial cancer. Similar to Lynch syndrome, these cancers can develop at a younger age than expected.

How is hereditary endometrial cancer diagnosed?

Most cases of endometrial cancer are not inherited. However, if you have a strong family history of endometrial cancer or an inherited genetic condition such as Lynch or Cowden syndrome, your doctor may recommend further assessment to determine whether you carry a gene mutation that increases your risk of developing endometrial cancer.

Genetic counselling and genetic testing

If you have a family history of hereditary cancers, your doctor may recommend genetic counselling as the first step. During the consultation, your genetic counsellor or specialist will review your family history, assess your inherited cancer risk, explain the benefits and limitations of genetic testing, and help you understand what your results may mean for you and your family.

If genetic testing is recommended, it is usually performed using a blood or saliva sample. A germline multi-gene panel test is commonly used because it can look for inherited genetic mutations associated with various hereditary cancer syndromes at the same time, such as Lynch syndrome (testing the MMR genes) or Cowden syndrome (testing the PTEN gene).

Whenever possible, testing is first offered to a family member who has already been diagnosed with cancer, as this can help identify whether an inherited mutation is present before testing other relatives.

Screening and diagnostic investigations

If you are found to have an inherited genetic condition or are considered to be at higher risk of endometrial cancer, your doctor may recommend regular monitoring.

This may include regular endometrial biopsy, where a small sample of tissue is collected from the lining of the uterus and examined for abnormal or cancerous cells. Transvaginal ultrasound may also be considered in selected situations, particularly after menopause.

Should you experience symptoms such as abnormal vaginal bleeding, or if a test result requires further investigation, your doctor may recommend further tests, including:

• Dilation and curettage (D&C), which may be recommended in selected cases to obtain a larger tissue sample for laboratory analysis.

• Imaging tests such as CT or MRI scans may also be performed if endometrial cancer is suspected or to determine the extent of the growth.

However, not every woman with an inherited genetic condition will develop endometrial cancer. Your specialist will recommend an individualised cancer screening plan based on your genetic findings, family history, age, and overall risk profile.

Who should consider genetic testing?

Germline genetic testing (such as a multi-gene panel that checks your inherited DNA) may be considered if your personal or family history suggests an inherited cancer syndrome. You may benefit from genetic counselling and further assessment for germline testing if you have: 

• Multiple close family members who have been diagnosed with endometrial or ovarian cancer.

• Family members who have had both endometrial and colorectal cancer, or other cancers associated with Lynch syndrome.

• A close relative who was diagnosed with a Lynch syndrome-related cancer before the age of 50.

• A known family history of Lynch syndrome, Cowden syndrome, or another inherited cancer syndrome.

If you experience any of the conditions mentioned above, further investigation may be worth considering. Schedule an appointment at Thomson Women's Clinic & Cancer Surgery to consult a gynaecological oncologist about your specific risks and whether genetic testing would be suitable for you.

What are the available treatments for endometrial cancer?

The most appropriate treatment for endometrial cancer depends on several factors, including the stage and grade of the cancer, whether it has spread beyond the uterus, your age, overall health, and your future fertility goals. Your gynaecological oncologist will recommend a personalised treatment plan based on your individual circumstances.

Treatment options for endometrial cancer may include:

Surgical treatment

Surgery is the primary treatment for most women with endometrial cancer. The most common procedure is a hysterectomy, which involves removing the uterus and cervix. Depending on the extent of the cancer, the ovaries, fallopian tubes, nearby lymph nodes, or surrounding tissues may also be removed to reduce the risk of the cancer spreading or recurring.

Non-surgical treatments

Depending on the stage of the cancer and your individual treatment plan, your specialist may also recommend one or more of the following treatments:

• Radiotherapy: which uses high-energy radiation to destroy cancer cells or reduce the risk of recurrence.

• Chemotherapy: which uses anti-cancer medicines to destroy cancer cells that may have spread beyond the uterus.

• Hormone therapy: which may be suitable for certain hormone-sensitive endometrial cancers or for women wishing to preserve fertility.

• Targeted therapy: which uses medicines that specifically target certain genetic or molecular changes within cancer cells.

Your doctor may also recommend immunotherapy to help your body's immune system recognise and attack cancer cells. This treatment is particularly effective for women whose endometrial cancer is linked to Lynch syndrome, as these specific hereditary tumours tend to respond well to immunotherapy drugs.

Your treatment may involve a combination of these approaches to achieve the best possible outcome. Your specialist will discuss the benefits, potential risks and expected outcomes of each option before recommending the most appropriate treatment plan for you.

When should you see a doctor?

Generally, it’s recommended to consult with your doctor or a gynaecological oncologist if you develop symptoms that could be associated with endometrial cancer or have concerns about inherited cancer risk. Early assessment can help identify the underlying cause of your symptoms and, if necessary, allow treatment to begin as early as possible.

Seek medical attention if you experience:

• Vaginal bleeding after menopause (12 months after your last menstrual period).

• Unusually heavy menstrual bleeding or bleeding between periods.

• Unusual vaginal discharge, particularly if it is watery, blood-stained, or has an unpleasant odour.

• Persistent pelvic or lower abdominal pain.

• Unexplained weight loss.

If you experience abnormal vaginal bleeding or other warning signs of endometrial cancer, seek medical attention promptly. Schedule an appointment with Thomson Women's Clinic & Cancer Surgery for a consultation with a gynaecological oncologist.

How can you help reduce the risk of endometrial cancer?

Although endometrial cancer cannot always be prevented, there are steps that may help lower your chances of developing it, particularly if you have certain risk factors or an inherited genetic condition. Your doctor can recommend a personalised prevention and cancer screening plan based on your medical history.

Strategies that may help reduce the likelihood of endometrial cancer include:

• Maintaining a healthy weight: aim to be physically active, as this can help to reduce excess oestrogen levels and lower the risk of endometrial cancer.

• Taking oral contraceptive pills (OCPs): long-term use of combined or progestogen-only oral contraceptives may help lower the risk of endometrial cancer, with the protective effect lasting for years after stopping the medication.

• Managing chronic health conditions: such as diabetes and metabolic disorders, through appropriate lifestyle measures and medical care.

• Considering the use of an intrauterine device (IUD): as some progesterone-containing IUDs have been associated with a lower risk of endometrial cancer.

FAQ

What factors can increase the risk of endometrial cancer?

What is the most common age for endometrial cancer?

Endometrial cancer is most commonly diagnosed in women between the ages of 55 and 64 years, with the average age at diagnosis being around 60 years. Although it predominantly affects women after menopause, it can occasionally occur in younger women, particularly those with inherited genetic conditions or certain hormonal and metabolic risk factors.

How fast does endometrial cancer spread?

What are the possible complications of endometrial cancer?

The information provided is intended for general guidance only and should not be considered medical advice. For personalised recommendations and advice based on your individual circumstances, schedule an appointment with Thomson Medical today.