Increased association between endometriosis and endometrial cancer: a nationwide population-based retrospective cohort study.

In the United States, endometrial cancer is the most common gynecological malignancy, with 46,470 new cases and 8120 deaths from the disease in 2011.1 Various conditions, including anovulation, polycystic ovarian syndrome, obesity, estrogen-only hormone replacement therapy, and tamoxifen use, lead to high levels of unopposed estrogen exposure, which have been linked to the pathogenesis of endometrial cancer.2,3 Although the exact mechanisms involved in endometrial carcinogenesis due to chronic estrogen exposure are unclear, it is thought that prolonged estrogen stimulation might enhance the pro-proliferative and inflammatory gene performance, which further induce DNA-damaging effects.4 Endometriosis is a common disease that affects 5% to 10% of women of reproductive age.5 Chronic inflammation has been linked to the establishment and progression of endometriosis, largely through the secretion of proinflammatory cytokines, inducing proliferation of peritoneal macrophages and mesothelial cells.6 Furthermore, several lines of evidence have linked endometriosis to excessive 17-estradiol signaling in the ectopic tissue. It was reported that elevated expression of P450 aromatase (CYP19A1) in endometriotic tissue leads to increased local production of 17-estradiol, which in turn promotes growth of the ectopic lesions.7–9 Endometriosis has been found to be associated with some histological subtypes (ie, clear cell and endometrioid carcinoma) of epithelial ovarian carcinoma, known as endometriosis-associated ovarian cancer (EAOC), which is etiologically distinct from other subtypes of ovarian cancer in several aspects.10 Studies have documented that endometriosis is associated with an approximately 3-fold risk for developing endometrioid and clear cell subtype. Patients with EAOC had a lower stage of cancer, a distribution of histological subtypes that differs from the general population, predominantly lower-grade endome triosis lesions, and significantly better overall survival as compared with other ovarian carcinomas.11 Although the association between endometriosis and some subtypes of ovarian cancer has been well established, the association between endometriosis and endometrial cancer is not as well defined as that in EAOC. However, clinical observation has shown that simultaneously detected endometrial and ovarian carcinomas are most often associated with endometrioid subtype, and ovarian endometriosis was identified in approximately 30% of these cases.12,13 Hence, there exists a potential association between endometriosis and endometrial cancer. From the above descriptions, it seems that endometriosis and endometrial cancer share common etiological mechanisms, including estrogen stimulation and chronic inflammation. As such, there is a putative association between these 2 disorders. In this work, we tested the hypothesis that endometriosis may increase the risk for developing endometrial cancer. We used a population-based national health registry database in Taiwan to explore the relationship between endometriosis and risk for subsequent development of endometrial cancer.