Risk factors for uterine cancer

A risk factor is something that increases the risk of developing cancer. It could be a behaviour, substance or condition. Most cancers are the result of many risk factors. But sometimes uterine cancer develops in women who don’t have any of the risk factors described below.

In Canada, the incidence rates for uterine cancer have been steadily rising for the past 30 years. Women who develop uterine cancer are usually over the age of 50. It is more common in Caucasian women than in other populations. Women living in North America or Europe develop uterine cancer more often than those living in other parts of the world.

Atypical endometrial hyperplasia is a precancerous condition of the uterus. It isn’t cancer, but it can sometimes become uterine cancer if it isn’t treated. Some of the risk factors for uterine cancer may also cause atypical endometrial hyperplasia. Find out more about precancerous conditions of the uterus.

Risk factors are generally listed in order from most to least important. But in most cases, it is impossible to rank them with absolute certainty.

Estrogen-only hormone replacement therapy (HRT)

Number of menstrual periods

Never giving birth

Overweight or obesity

Tamoxifen

Polycystic ovarian syndrome (PCOS)

Diabetes

Radiation therapy to the pelvis

Estrogen-producing ovarian tumours

Low levels of physical activity

Lynch syndrome

Cowden syndrome

There is convincing evidence that the following factors increase your risk for uterine cancer.

Hormone replacement therapy (HRT) uses female sex hormones (estrogen, progesterone or both) to manage the symptoms of menopause, such as hot flashes, vaginal dryness and mood swings. Research shows that using HRT with estrogen alone (without progesterone) increases the risk for uterine cancer. Taking estrogen combined with progesterone (called combined HRT) does not increase a woman’s risk for uterine cancer.

Women who have a higher number of menstrual periods during their lifetime have a greater risk of developing uterine cancer. This includes women who start having their period before the age of 12 (called early menstruation or early menarche) or their period stops after the age of 55 (called late menopause). Both early menstruation and late menopause mean that your body makes estrogen for a longer period of time, which increases your risk of developing uterine cancer.

Women who never give birth to a child are 2 times more likely to develop uterine cancer than women who give birth at least once. During pregnancy, estrogen levels in the body are lowered. The more times a woman gives birth, the less estrogen her body makes and the lower her risk of developing uterine cancer.

Women who are overweight or obese have a higher risk of developing uterine cancer. Those with a high amount of body fat can be up to 10 times more likely to develop uterine cancer.

Researchers don’t know the exact reason why overweight or obesity increases the risk for uterine cancer. It could be because having too much fat tissue raises the level of estrogen in the body, and too much estrogen increases the risk for uterine cancer. Obese people often have higher levels of insulin and insulin-like growth factor-1 in their blood, which can help some tumours grow. The risk for uterine cancer is even higher in overweight or obese women who have hypertension or diabetes.

Tamoxifen (Nolvadex, Tamofen) is a hormonal therapy drug used to treat certain cancers, most commonly breast cancer. Women treated with tamoxifen for 2 or more years have a higher risk of developing uterine cancer.

Polycystic ovarian syndrome (PCOS) is caused by changes to normal hormone cycles and the normal ovulation process. Many women with polycystic ovaries have few periods, or none at all, and may have difficulty getting pregnant. Women with PCOS have a higher risk of developing uterine cancer.

Diabetes (also called diabetes mellitus) is a chronic disease that leads to high blood sugar levels. Women with diabetes are about 2 times more likely to develop uterine cancer compared to women without the disease. Women with diabetes who are also obese or have high blood pressure have an even higher risk for uterine cancer.

Radiation therapy is used to treat certain cancers or bleeding from the uterus caused by a non-cancerous (benign) condition. Women who have high-dose radiation to the pelvis have a higher risk of developing uterine cancer.

Women with ovarian tumours that make estrogen have a higher risk for uterine cancer due to the higher estrogen levels.

Women who don’t get much physical activity have a higher risk of developing uterine cancer. Being active seems to protect against uterine cancer.

Lynch syndrome (also called hereditary non-polyposis colorectal cancer or HNPCC) is an inherited condition caused by a change (mutation) in one of the DNA mismatched repair genes. These genes normally correct mistakes when DNA is copied during cell division. With Lynch syndrome, mismatched repair genes don’t work properly and cells with mistakes are not repaired. Eventually, these abnormal cells build up and can become cancerous.

Women with Lynch syndrome have a greater risk of developing uterine cancer in their lifetime. Women with Lynch syndrome tend to develop uterine cancer at a younger age than women in the general population.

Cowden syndrome is an inherited condition that can cause many non-cancerous growths (called hamartomas) to form in the skin, breast, thyroid, colon, small intestine and mouth. Cowden syndrome is caused by a mutation in the PTEN gene. It increases the risk for uterine cancer.

The following factors have been linked with uterine cancer, but there is not enough evidence to show for sure that they are risk factors. More research is needed to clarify the role of these factors for uterine cancer.

• not being physically active (having sedentary habits)
• family history of uterine cancer
• high blood pressure (hypertension)
• contact with diethylstilbestrol (DES), which is a form of estrogen that is made in a lab
• high glycemic load, which is a measure of how quickly certain amounts of food raise blood sugar levels

Significant research shows that there is no link between intrauterine devices (a type of birth control) and a higher risk for uterine cancer.

To make the decisions that are right for you, ask your healthcare team questions about risks.