Relationship of benign gynecologic diseases to subsequent risk of ovarian and uterine tumors

Objective: Although endometriosis and uterine leiomyomas are common conditions, the extent to which either is associated with certain types of malignancies remains uncertain. Methods: Using record linkage techniques, we assessed the relationships between hospital and outpatient admissions for endometriosis or leiomyomas and the development of ovarian and uterine cancers in Denmark between 1978 and 1998. Based on a population-based cohort exceeding 99,000 women, including 2,491 ovarian cancers, 860 borderline ovarian tumors, and 1,398 uterine cancers, we derived relative risks (RR) and 95% confidence intervals (95% CI) associated with overall and histology-specific tumor risks after adjustment for calendar time and reproductive characteristics. Results: Endometriosis seemed to predispose to the development of ovarian cancer, with the association restricted to endometrioid or clear cell malignancies. Five or more years after the diagnosis of endometriosis, the RRs (95% CIs) were 2.53 (1.19-5.38) for endometrioid (7 exposed cases) and 3.37 (1.24-9.14) for clear cell (4 exposed cases) malignancies. Uterine leiomyomas were associated with increases in the risk of uterine malignancies, particularly sarcomas, where the RRs (95% CIs) were 20.80 (11.32-38.22) for women with 1 to 4 years of follow-up (11 exposed cases) and 5.70 (2.27-14.32) for those with more extended follow-up (5 exposed cases). Conclusion: In combination with clinical, pathologic, and molecular data, our results support that some endometriotic lesions may predispose to clear cell and endometrioid ovarian cancers. Uterine leiomyomas also showed a strong connection with subsequent uterine sarcomas, although it was difficult to decipher whether this reflected detection bias, shared risk factors, or an etiologic relationship.