Any substance or condition that increases cancer risk is referred to as a risk factor. There isn’t a known, single cause of uterine cancer. Most cancers are the result of many risk factors. However, some women with uterine cancer do not have any identifiable risk factors.
*Risk factors are generally listed in order from most significant to least significant. In most cases, it is impossible to rank the relative significance of individual risk factors with absolute certainty.
Post-menopausal women 45–70 years of age are at the highest risk of developing uterine cancer. Uterine cancer is more common in Caucasians 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. Women in higher income groups tend to be affected more than women in lower income groups.
The following factors are known to increase the risk of developing uterine cancer.
Estrogen replacement therapy
Women who receive estrogen only, without progesterone, as hormone replacement therapy after menopause are at higher risk of developing uterine cancer.
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Obesity
Obese women are at higher risk of developing uterine cancer because more estrogen is produced by the greater amount of fat. The risk is increased even more in obese women who have hypertension or diabetes. Being more than 50 pounds over the ideal body weight increases the risk of developing uterine cancer by about 10 times.
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Menstrual history
Early menarche (first menstruation) and late menopause (after the age of 52) means a longer time of estrogen exposure and higher risk of developing uterine cancer.
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Taking tamoxifen
Tamoxifen (Nolvadex, Tamofen) is a drug used to treat breast cancer. Women who are treated with this drug for 5 or more years are at higher risk of developing uterine cancer.
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Never giving birth
Women who have never had a full-term pregnancy (are nulliparous) are twice as likely to develop uterine cancer as women who have given birth at least once.
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Chronic anovulation
Women who do not ovulate (anovulation) during the menstrual cycle have a higher risk of developing uterine cancer. Anovulation may result from medical conditions, including hormonal imbalances and small cysts on the ovaries (polycystic ovary syndrome or Stein-Leventhal syndrome).
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Endometrial hyperplasia
Endometrial hyperplasia is an overgrowth of normal cells that line the uterus. It tends to progress to atypical hyperplasia, which is an overgrowth of abnormal cells. When untreated, approximately 1.6% of endometrial hyperplasias and 23% of atypical hyperplasias progress to uterine cancer.
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Previous pelvic radiation
Women who have received high-dose radiation to the pelvis are at a higher risk of developing uterine cancer. Pelvic radiation is used to treat other cancers or bleeding from the uterus caused by a benign (non-cancerous) condition.
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Diabetes
Diabetes increases the risk of uterine cancer. A woman is at even higher risk if she is also obese or has high blood pressure (hypertension).
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Estrogen-secreting ovarian tumours
Estrogen-secreting ovarian tumours are usually removed by surgery. At the time of surgery, uterine cancer is found in 6%–21% of women with estrogen-secreting tumours.
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Hereditary non-polyposis colon cancer (HNPCC)
Hereditary non-polyposis colorectal cancer (HNPCC) is also known as Lynch syndrome.
HNPCC is an inherited condition that affects the genes that normally correct mistakes when DNA is copied during cell division (mismatched repair genes). As a result, cells with genetic mistakes are not repaired. Eventually, these abnormal cells build up and can become cancerous.
Women with HNPCC have a greater lifetime risk of developing uterine cancer. Uterine cancer also develops at a much younger age in women with HNPCC, before the age of 45.
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Possible risk factors
The following factors have some association with uterine cancer, but there is not enough evidence to say they are known risk factors. Further study is needed to clarify the role of these factors for uterine cancer.
- family history – A few studies have looked at a woman’s risk of developing uterine cancer if she has one or more first-degree relatives who have had uterine cancer. At present, it is unknown if the connection between having a family history of uterine cancer and developing uterine cancer is due more to shared genes or to shared environment and behaviours among female family members.
- hypertension – High blood pressure appears to increase the risk of uterine cancer. A woman may be at even higher risk if she is also obese or has other risk factors.
- gallbladder disease – Researchers have found that a history of gallbladder disease increases the risk of developing uterine cancer. However, the risk may be from other factors linked to gallbladder disease, such as obesity and the use of estrogen replacement therapy.
- inherited cancer syndromes – Studies have shown more cases of uterine cancer in women who have or at risk for:
- Cowden syndrome (mutation to the tumour-suppressor gene PTEN)
- p53 gene mutation
- diethylstilbestrol (DES) exposure – DES is a form of estrogen that was used between 1940 and 1971 to treat women with certain problems during pregnancy (such as miscarriage). It has not been approved for use in pregnant women since the 1970s. Daughters of women who took DES during their pregnancy may have a higher than average risk of developing uterine cancers.
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Factors not associated with uterine cancer
Intrauterine devices are not considered to be a risk factor for uterine cancer because there is significant evidence showing that there is no association.
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Unknown risk factors
The following are factors for which there is not enough evidence or the evidence is inconclusive. In other words, it can’t be determined for sure whether these risk factors are or are not associated with uterine cancer.
- diet
- alcohol
- environmental chemical exposure
- human papillomavirus (HPV) infection
- sedentary behaviour (sitting too much)
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See a list of questions to ask your doctor about risks.