The Connection Between Endometriosis and Cancer

Reviewed by: HU Medical Review Board | Last reviewed: June 2018

The association between endometriosis and cancer has been of interest to experts for decades. Although research into this potential relationship has been performed for some time, much more needs to be investigated in order to better understand the many dynamics at work. The most common sites of cancers thought to be associated with endometriosis are in the female reproductive system, most frequently, the ovaries.

It is important to note, however, that malignant transformation of endometriosis, otherwise known as cancer development related to endometriosis lesions, is extremely rare. This transformation has only been reported in roughly 1% of all cases of endometriosis.1,2 Further, transformation of endometriosis into cancer is only thought to be possible in atypical endometriosis lesions.4-6 Atypical endometriosis lesions are also very rare. As an example, atypical endometriosis has been reported in only 2-3% of all excised ovarian endometriomas, and it has even been suggested that this proportion is an overestimate.3 The diagnosis of cancer in individuals with endometriosis may be the result of a malignant transformation, however, it may also be due to common risk factors shared between both conditions, such as irregularities in hormone regulation, immune system-related issues, and genetic predisposition.1,6

How does cancer develop?

Cancer is characterized by unregulated cell growth and development. In the body, healthy cells grow and divide at a regulated rate, and cells that are trying to multiply must pass various "checkpoints" that monitor for issues such as mutations. As an example, a cell that has a mutation, or who's DNA was not correctly copied before it started trying to multiply, may get stuck in the replication cycle when it didn't successfully pass a checkpoint. This prevents faulty cells from dividing and increasing in numbers throughout the body. These checkpoints also prevent cells from multiplying too much in general. Occasionally, mutations may go undetected or may affect a gene responsible for performing these checkpoints. When this happens, cell growth can go unregulated, and cells can become cancerous. Cancerous cells often possess serious mutations and divide rapidly, forming tumors.

How might endometriosis affect the development of cancer?

The mechanism by which atypical endometriosis lesions might directly transform into malignancies is not well understood. A common theory is that the cells that make up endometriosis lesions may have some of the same genetic markers or genetic mutations that cancer cells have. Some of these may include mutations (or a risk of future mutations) within genes responsible for preventing tumors or running cell cycle checkpoints.1,6

Outside of direct transformation, some experts have theorized that the association between certain cancers and endometriosis may be due to shared risk factors, as well as endometriosis creating an environment suitable for cancer growth. Common risk factors for endometriosis include irregularities in hormone regulation (specifically the regulation of estrogen), genetics or familial history of the condition, and potential immune system-related issues. These are all shared risk factors with cancers of the female reproductive system and surrounding structures. This overlap may be a reason why an individual with endometriosis may also be at risk for developing certain cancers.

Additionally, endometriosis creates areas of constant inflammation. Inflammation is another risk factor for developing cancer, and healthy cells residing in areas of chronic inflammation may have a higher risk of experiencing mutations, including those responsible for cancer development.1 As mentioned, much more research is needed to further characterize the relationship of cancer and endometriosis, as well as its shared risk factors.

What types of cancer are associated with endometriosis?

Of the 1% of endometriosis cases that have malignant transformation, 80% of these result in a type of ovarian cancer.2 The most common types of ovarian cancer experienced are endometrioid adenocarcinoma (EAD) and clear cell carcinoma (CCC).1,6

Despite the ovaries being the most common site of malignant transformation of endometriosis, the overall increase in risk of experiencing ovarian cancer is still very low. Among all women, the risk of developing ovarian cancer is one out of every 76 females. This is roughly 1.3% of all women, regardless of endometriosis status. In contrast, the risk of developing ovarian cancer in women affected by endometriosis is less than two out of every 100 women. This amounts to roughly 1.8% of all women with endometriosis.7 Put another way, the average woman has about a 99% chance of never developing ovarian cancer, while women with endometriosis have about a 98.5% chance of never developing the condition. The overall risk of developing ovarian cancer is less than 2% even with endometriosis, which is still very low.3

Aside from the ovaries, the next most common sites of malignant transformation are the rectovaginal septum (the space between the vagina and rectum), colon, vaginal wall, and intestinal wall.1,6 Although exceedingly rare, malignant transformation can occur at the site of a caesarean section (C-section) scar when endometrial cells were accidentally transported during surgery.2 Other cancers that may have an association with endometriosis in general are breast cancer, colorectal cancer, endometrial cancer, and non-Hodgkin lymphoma, however, much more research is needed to investigate these associations as well.6

How do I decrease my risk of cancer?

Although there is no concrete method to preventing cancer, there are behaviors you can practice to potentially decrease your risk. Some of these include, but are not limited to, eating a healthy diet, eliminating the use of tobacco, maintaining a healthy weight, and exercising regularly.8 Additionally, it's important to attend regular doctor's appointments and to follow your doctor's instructions regarding cancer screenings, such as receiving annual pap smears or regular mammograms. These screening guidelines may vary from person to person, and depend on a variety of factors. As an example, regular screening for ovarian cancer is not always recommended for women with endometriosis. Your provider or healthcare team will be able to advise you on what tests you may need, and when you should receive them.

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