Genetics of Endometriosis-Associated Ovarian Cancer: A Systematic Review - 26/03/26

Doi : 10.1016/j.jogoh.2026.103170

Bijan Morshedi ^a, Elizabeth Schlant ^b, Lili Mohebbi ^c, Bronwyn S Bedrick ^b, Laura Courtright ^b, Gaelle Massoud ^b, Jiahui Zhang ^d, Morgan Snow ^b, Rubén Fernández Ibáñez ^e, Elisabeth Nylander ^b, Ie-Ming Shih ^b,^e, Tian-Li Wang ^b,^e, Rebecca Stone ^b, James Segars ^b, Bhuchitra Singh ^b,^⁎

^a Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia, USA

^b Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

^c Department of Obstetrics and Gynecology, Northwell Hofstra, Staten Island University Hospital, Staten Island, New York, USA

^d Department of Obstetrics and Gynecology, University of Vermont Medical Center, Burlington, Vermont, USA

^e Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

^⁎ Corresponding author: Bhuchitra Singh, MD, MPH, MS, MBA, Division of Reproductive Sciences & Women’s Health Research, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research Building, Room 624, Baltimore, MD, 21205, Phone: 410-614-2000, Fax: 410-614-7060. Division of Reproductive Sciences & Women’s Health Research Department of Gynecology & Obstetrics Johns Hopkins University School of Medicine 720 Rutland Avenue, Ross Research Building, Room 624 Baltimore MD 21205

Sous presse. Manuscrit accepté. Disponible en ligne depuis le Thursday 26 March 2026

Abstract

Objective

Up to 1.6% of patients with endometriosis develop epithelial ovarian carcinoma. The genetic overlap between endometriosis and ovarian cancer has not been fully characterized. This review aims to describe the current literature on mutations correlated with endometriosis-associated epithelial ovarian carcinoma.

Methods

In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO ID: CRD42023400697), Cochrane Library, Embase, PubMed, Scopus, and Web of Science Core Collection databases were queried from January 1 ^st , 1995, to April 1 ^st , 2022 for English language studies on the genetic basis of endometriosis-associated epithelial ovarian carcinoma. The quality of included studies was assessed using the Newcastle-Ottawa Scale.

Results

Search criteria yielded 18,639 articles, of which 30 met inclusion criteria. 70 genes were assessed in the 30 included studies, and 9 of these appeared in two or more studies. The most frequently mutated genes were PIK3CA, PTEN, ARID1A and CTNNB1. None of these genes had a mutation frequency greater than 0.5 when data from all 30 studies were aggregated. Stratification by epithelial ovarian cancer subtype revealed an association between CTNNB1 mutation and endometrioid carcinoma (47/97; 48.4%) compared to clear cell carcinoma (4/38; 10.5%) (p = 0.00004).

Conclusions

Due to the low mutation frequency of commonly studied genes, cumulative mutational burden may better explain the progression and pathogenesis of endometriosis-associated epithelial ovarian carcinoma than any single mutation. CTNNB1 may be associated with the development of endometrioid ovarian carcinoma. Future studies may consider the use of polygenic scores for risk assessment of endometriosis-associated ovarian cancer.

Le texte complet de cet article est disponible en PDF.

Keywords : endometriosis-associated ovarian cancer, endometriosis, ovarian cancer, CTNNB1, endometrioid ovarian carcinoma, clear cell ovarian carcinoma