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. 2024 Aug 13;332(6):482-489.
doi: 10.1001/jama.2024.9210.

Endometriosis Typology and Ovarian Cancer Risk

Mollie E Barnard  1   2   3 , Leslie V Farland  4 , Bin Yan  5 , Jing Wang  5 , Britton Trabert  1   2   6 , Jennifer A Doherty  1   2 , Huong D Meeks  1   7 , Myke Madsen  1 , Emily Guinto  1 , Lindsay J Collin  1   2 , Kathryn A Maurer  1   6   8 , Jessica M Page  9 , Amber C Kiser  10 , Michael W Varner  6 , Kristina Allen-Brady  11 , Anna Z Pollack  12 , Kurt R Peterson  13 , C Matthew Peterson  6 , Karen C Schliep  5
Affiliations

Endometriosis Typology and Ovarian Cancer Risk

Mollie E Barnard et al. JAMA. .

Abstract

Importance: Endometriosis has been associated with an increased risk of ovarian cancer; however, the associations between endometriosis subtypes and ovarian cancer histotypes have not been well-described.

Objective: To evaluate the associations of endometriosis subtypes with incidence of ovarian cancer, both overall and by histotype.

Design, setting, and participants: Population-based cohort study using data from the Utah Population Database. The cohort was assembled by matching 78 893 women with endometriosis in a 1:5 ratio to women without endometriosis.

Exposures: Endometriosis cases were identified via electronic health records and categorized as superficial endometriosis, ovarian endometriomas, deep infiltrating endometriosis, or other.

Main outcomes and measures: Estimated adjusted hazard ratios (aHRs), adjusted risk differences (aRDs) per 10 000 women, and 95% CIs for overall ovarian cancer, type I ovarian cancer, and type II ovarian cancer comparing women with each type of endometriosis with women without endometriosis. Models accounted for sociodemographic factors, reproductive history, and past gynecologic operations.

Results: In this Utah-based cohort, the mean (SD) age at first endometriosis diagnosis was 36 (10) years. There were 597 women with ovarian cancer. Ovarian cancer risk was higher among women with endometriosis compared with women without endometriosis (aHR, 4.20 [95% CI, 3.59-4.91]; aRD, 9.90 [95% CI, 7.22-12.57]), and risk of type I ovarian cancer was especially high (aHR, 7.48 [95% CI, 5.80-9.65]; aRD, 7.53 [95% CI, 5.46-9.61]). Ovarian cancer risk was highest in women with deep infiltrating endometriosis and/or ovarian endometriomas for all ovarian cancers (aHR, 9.66 [95% CI, 7.77-12.00]; aRD, 26.71 [95% CI, 20.01-33.41]), type I ovarian cancer (aHR, 18.96 [95% CI, 13.78-26.08]; aRD, 19.57 [95% CI, 13.80-25.35]), and type II ovarian cancer (aHR, 3.72 [95% CI, 2.31-5.98]; aRD, 2.42 [95% CI, -0.01 to 4.85]).

Conclusions and relevance: Ovarian cancer risk was markedly increased among women with ovarian endometriomas and/or deep infiltrating endometriosis. This population may benefit from counseling regarding ovarian cancer risk and prevention and could be an important population for targeted screening and prevention studies.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Barnard reported receiving grants from National Cancer Institute (NCI) during the conduct of the study and personal fees from Epi Excellence LLC outside the submitted work. Dr Farland reported receiving grants from National Institutes of Health during the conduct of the study. Dr Doherty reported receiving pilot grant funding from the Huntsman Cancer Institute Breast and Gynecologic Cancers Center at the University of Utah, other from NCI’s Surveillance, Epidemiology, and End Results (SEER) Program (contract No. HHSN261201800016I), and additional support from the University of Utah and Huntsman Cancer Foundation. Dr Collin reported receiving grants from NCI during the conduct of the study and personal fees from Epidemiologic Research & Methods, LLC outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Time-Dependent Association of Endometriosis and Ovarian Cancer, Adjusted for Birth State, Birth Year, Age at First Endometriosis Diagnosis, and Parity
For this model, 3 knots (x-axis values of the join points) were chosen based on percentiles from the whole cohort (20% [n = 94 813], 50% [n = 236 475], and 85% [n = 393 530]). The plot and corresponding time-specific adjusted hazard ratios (aHRs) indicate a possible U-shaped relationship. At 5 years, the aHR was 3.72 (95% CI, 3.07-4.76), at 10 years the aHR was 1.09 (95% CI, 0.88-1.55), and at 20 years the aHR was 3.45 (95% CI, 2.50-4.26).
Figure 2.
Figure 2.. Adjusted Hazard Ratios (aHRs) Comparing Risk of Ovarian Cancer Among Women With vs Without Endometriosis
Results for each endometriosis subtype are presented separately for all histotypes of ovarian cancer: type I (endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous). Although a positive association was observed for all possible combinations of endometriosis subtypes and ovarian cancer histotypes, the association between deep infiltrating and/or ovarian endometriomas and type I ovarian cancer was greatest in magnitude. Per Utah Department of Health and Human Services confidentiality requirements, counts less than 11 are not reported and any counts that could be used to calculate those less than 11 for another category are not provided. Whiskers indicate 95% CIs.
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Comment in

References

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