Causes and Risk Factors of Endometrial Cancer

Endometrial cancer affects the lining of the uterus, the endometrium, and is the most common form of uterine cancer. This type of cancer occurs when the cells in the endometrium begin to mutate, multiply, and build up too rapidly, forming a mass or tumor. Endometrial cancer can spread to other parts of your body as well, but it's typically diagnosed in the early stages. Although the direct causes of endometrial cancer are unknown, researchers have identified a genetic link and a number of risk factors for the disease, primarily related to excess exposure to estrogen.

Genetics

A gene mutation or genetic disorder may increase your risk of endometrial cancer. With that in mind, some other cancers can be "red flags" for endometrial cancer risk, as they have the potential of having the same genetic underpinnings.

One genetic disorder that contributes to a high risk of endometrial cancer is hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome. This condition increases your risk of certain cancers, especially colon cancer, endometrial cancer (your likelihood of developing it is 40 percent to 60 percent), and ovarian cancer. You're also more likely to be diagnosed with endometrial cancer at a younger age.

The gene mutation associated with HNPCC is passed from parents to children. If anyone in your family has HNPCC or if you've been diagnosed with it, talk to your healthcare provider about cancer screenings you should undertake. Being aware of your elevated risk and being proactive about testing can lead to early detection and successful treatment in the event that you develop cancer.

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Other genetic factors that may increase the risk of endometrial cancer include:

• BRCA mutations: This mutation in either the BRCA 1 or BRCA 2 genes puts you at high risk for developing breast and ovarian cancer. There have been some studies that show that women with this mutation seem to have a higher risk of developing endometrial cancer as well.
• Cowden syndrome: This genetic disorder causes an increased risk of developing certain cancers, especially endometrial cancer, breast cancer, colorectal cancer, kidney cancer, and thyroid cancer.
• Undiscovered disorders: Endometrial cancer may be common in some families, so it's possible that, in these cases, there's a genetic disorder or defect that hasn't been identified yet.

Health Risk Factors

While risk factors may increase your chances of developing endometrial cancer, they do not mean you will get it or, if you do, that they necessarily caused the cancer. The American Cancer Society notes that many women with one or more risk factors never develop endometrial cancer, while some women who end up with this cancer have no known risk factors at all.

Endometrial cancer is more common in women beyond the age of menopause, so your risk increases as you get older (the mean age of diagnosis is 62).

Estrogen Exposure

While we cannot yet pinpoint exactly what causes endometrial cancer, studies suggest that higher levels of estrogen and longer exposure to estrogen over many years may be associated with endometrial cancer development.

Estrogen is a naturally occurring hormone made in the ovaries, along with the hormone progesterone. These hormone levels fluctuate during your menstrual cycle. During and after menopause, the body stops producing these hormones, which is what causes symptoms like hot flashes, night sweats, and vaginal dryness.

Excess estrogen exposure can occur in these situations:

• Estrogen-only hormone therapy: To alleviate the bothersome side effects of menopause, some women are prescribed hormone replacement therapy. This can be either estrogen or estrogen combined with progestin (a synthetic version of progesterone). Estrogen can cause the lining of the uterus to grow (endometrial hyperplasia), so progestin is used to counteract this effect. Taking estrogen alone without the aid of progestin when you still have your uterus may increase your risk of endometrial cancer.
• Tamoxifen use: Tamoxifen is an adjuvant therapy drug often prescribed for women with breast cancer. It binds to estrogen receptors in some tissues, blocking estrogen from stimulating tissue growth and preventing estrogen from fueling some types of breast cancer. Unfortunately, Tamoxifen can also stimulate the growth of the endometrium, which can lead to endometrial cancer.
• Polycystic ovary syndrome or irregular ovulation: If you experience irregular ovulation, like polycystic ovary syndrome (PCOS), you face an increased risk of endometrial cancer. In women with irregular ovulation, estrogen is being produced and stimulating the growth (thickening) of the endometrial lining. However, if ovulation does not occur, the endometrial lining is not shed as it is in normal, ovulating women and, thus, is exposed to more estrogen. The result can be endometrial hyperplasia (thickening), which can lead to endometrial cancer.
• Many years of menstruation: Starting menstruation early (before age 12) and/or beginning menopause late (after age 50) also increases your risk of endometrial cancer. In menstruating women, the endometrium is exposed to estrogen during every cycle. The more cycles you have, the more estrogen exposure your endometrium experiences.
• Obesity: Even though the ovaries are no longer producing estrogen after menopause as they once were, estrogen can still be found in the body in fat or adipose tissue. This is normal for all women. Researchers believe that because obese women have more adipose tissue, they are at an increased risk of developing endometrial cancer due to higher levels of estrogen. Unfortunately, women who are obese and also have endometrial cancer suffer from an increased risk of death from the disease. Keep in mind that women at healthy weights are also vulnerable to endometrial cancer.
• Never being pregnant: Women who have never been pregnant are at an increased risk, especially those who have fertility issues. When you're pregnant, your hormones shift toward producing more progesterone than estrogen, so every pregnancy gives you a little more protection from endometrial cancer simply by giving your body a bit of a break from the hormone.
• Granulosa cell tumor: There is a rare type of ovarian tumor, a granulosa cell tumor, that secretes estrogen, causing high estrogen levels and raising the risk of developing endometrial cancer.

Certain Illnesses

If you have or have had any of these conditions, your risk of developing endometrial cancer is higher:

• Diabetes
• High blood pressure
• Endometrial hyperplasia
• Breast cancer
• Ovarian cancer
• Family history of endometrial or colon cancer
• Gallbladder disease

Pelvic radiation therapy, used to kill some types of cancer, can cause damage to the DNA of other cells, which may increase the risk of developing a secondary cancer, including endometrial cancer.

Lifestyle Risk Factors

There are some lifestyle risk factors that can contribute to your risk of developing endometrial cancer as well, including:

• Having a sedentary lifestyle: Research shows that physical activity lowers your risk of developing endometrial cancer; conversely, being sedentary increases your risk. Try to get at least 30 minutes of exercise a day to help decrease your risk, especially if you have additional risk factors.
• Eating a high-fat diet: Not only does a high-fat diet by itself increase the risk of endometrial cancer and other cancers, it can lead to obesity, which is another risk factor. If you consume more fat than you should, work to reduce your fat intake and to eat healthy, well-balanced meals. If you're obese, this means you can tackle two risk factors at once—a high-fat diet and obesity.