Uterine cancer occurs when cells in the uterus, a hollow organ in the female reproductive system where a fetus develops during normal pregnancy, mutate and grow uncontrollably.
Uterine cancer most commonly starts in the endometrium.
Some research suggests that hormones and gene mutations may play a role in the development of uterine cancer. Still, more research is needed to determine how hormonal imbalances and gene mutations can cause uterine cancer.
Hormonal Imbalance
The cells in the endometrium (the lining of the uterus) have hormone receptors for the sex hormones estrogen and progesterone. These hormones affect the growth of endometrial cells. Over time, increased growth may develop into cancer.
Many uterine cancer risk factors are related to hormone levels in the body. Most cases are associated with increased levels of estrogen in the body. While researchers believe that hormonal imbalances affect uterine cancer risk, the connection is still not clear.
Gene Mutations
Cancer of any type occurs when cells grow uncontrollably. This happens when a cell’s DNA (genetic material) mutates (changes). Mutations (genetic changes) may affect how cells grow, divide, and multiply. Your risk of uterine cancer increases if you experience gene mutations in the cells of your uterus.
Gene mutations can happen for several reasons, including:
- Mistakes that happen during regular cell division
- Harmful substances
- Inherited gene mutations
Researchers believe that some people with uterine cancer inherited gene mutations from their parents that increased their risk of cancer. Mutations in the PTEN, KRAS, and TP53 genes may affect your risk of uterine cancer.
Uterine cancer may be hereditary for some people. A hereditary condition is one that can be inherited from your parents through gene mutations.
Hereditary nonpolyposis colon cancer (HNPCC), also referred to as Lynch syndrome, is a hereditary genetic condition that increases the risk of uterine cancer and some other cancers. Lynch syndrome increases the risk of uterine cancer by causing gene mutations in one or more of the following genes:
- MLH1
- MSH2
- MLH3
- MSH6
- TGBR2
- PMS1
- PMS2
When these genes function abnormally, the cell’s DNA can’t repair itself. This may lead to DNA mutations and uncontrolled cell growth. Up to 70% of people with Lynch syndrome may have uterine cancer at some point in their lives, compared to 3% in the general population.
Depending on your age, sex, and ethnicity, you may be more likely to develop uterine cancer than others.
- Age: The risk of uterine cancer goes up as you get older. You may be most at risk if you’re over 50, with most diagnoses occurring after menopause.
- Sex: People with a uterus can develop the cancer.
- Ethnicity: Uterine cancer, especially more aggressive forms with worse outlooks, is more common in people who are Black than in other groups. The risk may be due to higher rates of obesity and diabetes, but more research is needed to understand the disparity.
While researchers do not know the exact cause of uterine cancer, they have identified several risk factors for the disease.
Having a risk factor doesn’t mean that you will definitely develop uterine cancer. Some people with cancer do not have any risk factors, and people with several risk factors don’t always have uterine cancer. You may be able to change some of your risk factors, too.
Obesity
Obesity is a strong risk factor for uterine cancer. Obesity can affect hormone levels, which may cause cells in the endometrium to change and grow uncontrollably. Having more fat tissue can increase your estrogen levels because fat cells may change certain hormones into estrogen.
Research shows that endometrial cancer is three times as common if you have obesity. Talk with your healthcare provider if you are concerned about your weight as it relates to cancer risk.
Hormonal Changes
Your hormone levels and their balance may impact your uterine cancer risk. A balance between the hormones estrogen and progesterone helps keep your endometrial tissue healthy and prevents overgrowth. A hormonal imbalance may increase the risk of endometrial cancer.
Several factors may affect your hormone levels, including:
- Hormone replacement therapy (HRT): During menopause, your estrogen levels significantly decrease. Estrogen treatment may help to treat menopause symptoms, but estrogen therapy without progesterone may increase the risk of endometrial cancer.
- Number of menstrual cycles: Having more menstrual cycles in your lifetime increases the risk of endometrial cancer by exposing you to more estrogen. You may have a higher risk if your periods began before age 12 or if you went through menopause later in life.
- Never being pregnant: Pregnancy increases the amount of progesterone in the body, which improves hormonal balance. People who have never been pregnant are at an increased risk of endometrial cancer.
- Tamoxifen use: Tamoxifen is a drug that treats breast cancer. It increases estrogen in the uterus and may cause the endometrium to grow. In general, though, the risk of uterine cancer from tamoxifen use is low.
- Ovarian tumors: Certain types of ovarian tumors produce estrogen and lead to high estrogen levels in the body.
- Polycystic ovarian syndrome (PCOS): People with PCOS have high levels of estrogen and certain male hormones known as androgens. They also tend to have low levels of progesterone.
Lifestyle Factors
Diet and physical activity can affect your risk of uterine cancer.
A high-fat diet can increase the risk of several types of cancer, including uterine cancer. A diet high in fat and calories also increases the risk of obesity, another risk factor for uterine cancer.
Physical activity is an important way to lower your cancer risk. Being inactive or sitting too much may be linked to an increased risk of uterine cancer.
Diabetes
People with diabetes are at an increased risk of uterine cancer. It’s twice as common in people with type 2 diabetes than in those without the condition. The connection is not clear, but it may be because type 2 diabetes is more common in people with obesity.
History of Breast Cancer or Ovarian Cancer
Having a history of breast cancer or ovarian cancer increases your risk of uterine cancer. These cancers share many of the same risk factors. Radiation therapy to the pelvic area, which may rarely be a treatment for ovarian cancer, also increases the risk of uterine cancer.
Endometrial Hyperplasia
Endometrial hyperplasia is a condition that causes the endometrium to grow, and this increased growth can lead to cancer. If left untreated, up to 8-29% of people with endometrial hyperplasia will develop endometrial cancer, with a four-times higher risk associated with the presence of atypical cells.
Uterine cancer is a type of cancer that develops in the tissues of the uterus. Researchers don’t know the exact cause of uterine cancer but have determined that hormonal imbalances and gene mutations likely play a role.
Risk factors for uterine cancer include older age, obesity, and factors that affect your hormone levels. These include chronic conditions like PCOS, ovarian tumors, and certain types of cancer. Other risk factors include hormonal therapies, diet, lack of exercise, and diabetes.
