Endometriosis is a chronic condition defined by the growth of tissue similar to the lining of the uterus (endometrium) outside the uterine cavity, most commonly in the pelvic area and on the ovaries. This misplaced tissue responds to hormonal cycles, leading to inflammation, scarring, and persistent pain. Ovarian cancer is a serious malignancy involving the uncontrolled growth of abnormal cells in the ovaries or fallopian tubes. While distinct, a recognized biological connection exists between endometriosis and the development of certain ovarian cancer subtypes. This association raises questions about how a benign condition may sometimes progress to a malignancy.
Understanding the Relative Risk
The question of increased risk requires distinguishing between relative and absolute risk. For most women with endometriosis, the absolute lifetime risk of developing ovarian cancer remains very low, generally estimated to be under two percent. The overall lifetime risk for the general female population is approximately 1.3 percent, meaning the difference in absolute terms is small.
Endometriosis does raise the relative risk of ovarian cancer. Studies show women with endometriosis have a relative risk increase of approximately 1.5 to 2.0 times compared to women without the condition. While the baseline risk is low, this diagnosis doubles the statistical likelihood of developing the disease. For women with severe forms of ovarian endometriosis, such as large endometriomas, the relative risk has been reported to be even higher, suggesting a link between disease severity and potential for malignant transformation.
Subtypes Linked to Endometriosis
The association between endometriosis and ovarian cancer is highly specific, involving a distinct group of malignancies known as Endometriosis-Associated Ovarian Cancers (EAOCs). These cancers are typically Type I ovarian tumors, which are slower-growing and less aggressive than the common high-grade serous carcinomas. The two most frequently linked subtypes are Clear Cell Carcinoma (CCC) and Endometrioid Carcinoma (EC).
Endometriosis is estimated to be present in up to 35 percent of CCC cases and around 27 percent of EC cases. This strong association suggests that ectopic endometrial tissue, especially within an ovarian endometrioma, acts as the tissue of origin for these specific cancers. Malignant transformation is thought to be preceded by a specific tissue change known as Atypical Endometriosis or Endometriosis-Related Intraepithelial Neoplasia (ERIN). This premalignant change is characterized by cellular atypia and is considered the biological bridge between the benign endometriotic cyst and the invasive cancer.
Biological Pathways to Malignancy
The transformation of benign endometriotic tissue into cancer is a complex process driven by several interconnected biological pathways. Chronic inflammation is a significant factor, as cyclic bleeding within endometriomas releases blood products, particularly iron, leading to oxidative stress. This persistent inflammatory microenvironment generates reactive oxygen species, which damage cellular DNA and promote genetic instability.
The hormonal environment also plays a role, as the growth of endometriosis and the development of some EAOCs are dependent on estrogen. This hyperestrogenic state drives the proliferation of ectopic tissue, increasing the likelihood of random genetic errors during cell division. A specific genetic alteration frequently implicated in this transformation is the loss of function in the ARID1A tumor suppressor gene.
Mutations in ARID1A are found in a high percentage of Clear Cell Carcinomas (46 to 57 percent) and Endometrioid Carcinomas (approximately 30 percent). This gene codes for a protein component of a chromatin remodeling complex. The loss of ARID1A function is considered an early event in pathogenesis, often co-occurring with other mutations like those in the PIK3CA gene, which further drives uncontrolled cell growth.
Surveillance and Management Strategies
Given the established link, women with endometriosis, particularly those with ovarian endometriomas, should engage in active monitoring and open communication with their healthcare providers. Regular pelvic examinations are standard follow-up care. For those with endometriomas, periodic transvaginal ultrasounds monitor for changes in cyst size or internal structure, such as the development of mural nodules, which could indicate transformation.
Awareness of persistent or changing symptoms is important, even though symptoms like bloating, pelvic pain, and changes in bowel or bladder habits are common with endometriosis. Any significant deviation from a patient’s usual symptom pattern should be promptly discussed with a doctor. Routine cancer screening with blood tests like CA-125 is not recommended for the general endometriosis population, but it may be selectively used with imaging for high-risk individuals.
Effective management of endometriosis, such as long-term use of combined hormonal contraceptives, is associated with a reduction in the relative risk of ovarian cancer. Surgical removal of large or recurrent endometriomas, especially when approaching menopause, may be considered a risk-reduction strategy. In specific cases, a bilateral salpingectomy (removal of the fallopian tubes) may also be discussed to reduce ovarian cancer risk.