Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies

Abstract

Background: Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer.

Methods: Data from 13 ovarian cancer case-control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models.

Findings: 13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13 226 controls, odds ratio 3·05, 95% CI 2·43-3·84, p<0·0001), low-grade serous (31 [9·2%] of 336 cases, 2·11, 1·39-3·20, p<0·0001), and endometrioid invasive ovarian cancers (169 [13·9%] of 1220 cases, 2·04, 1·67-2·48, p<0·0001). No association was noted between endometriosis and risk of mucinous (31 [6·0%] of 516 cases, 1·02, 0·69-1·50, p=0·93) or high-grade serous invasive ovarian cancer (261 [7·1%] of 3659 cases, 1·13, 0·97-1·32, p=0·13), or borderline tumours of either subtype (serous 103 [9·0%] of 1140 cases, 1·20, 0·95-1·52, p=0·12, and mucinous 65 [8·5%] of 767 cases, 1·12, 0·84-1·48, p=0·45).

Interpretation: Clinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer.

Funding: Ovarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation.

Figure 1

Association between endometriosis and subtypes of ovarian cancer (A) Invasive. (B) Borderline. Data are site-specific stratified and adjusted ORs (squares) and 95% CI (horizontal lines). AUS=Australian Cancer Study, Australian Ovarian Cancer Study. GER=German Ovarian Cancer Study. MAL=Malignant Ovarian Cancer Study. UKO=United Kingdom Ovarian Cancer Population Study. CON=Connecticut Ovary Study. DOV=Diseases of the Ovary and their Evaluation Study. HAW=Hawaii Ovarian Cancer Study. HOP=Hormones and Ovarian Cancer Prediction Study. MAY=Mayo Clinic Ovarian Cancer Study. NCO=North Carolina Ovarian Cancer Study. NEC=New England Case-Control Study of Ovarian Cancer. UCI=University of California, Irvine Ovarian Cancer Study. USC=University of Southern California, Study of Lifestyle and Women's Health., OR=odds ratio.

Figure 2

Association between endometriosis and subtypes of invasive ovarian cancer (A) Clear-cell. (B) Endometrioid. (C) Mucinous. (D) High-grade serous. (E) Low-grade serous. Data are site-specific stratified and adjusted ORs (squares) and 95% CI (horizontal lines). AUS=Australian Cancer Study, Australian Ovarian Cancer Study. GER=German Ovarian Cancer Study. MAL=Malignant Ovarian Cancer Study. UKO=United Kingdom Ovarian Cancer Population Study. CON=Connecticut Ovary Study. DOV=Diseases of the Ovary and their Evaluation Study. HAW=Hawaii Ovarian Cancer Study. HOP=Hormones and Ovarian Cancer Prediction Study. MAY=Mayo Clinic Ovarian Cancer Study. NCO=North Carolina Ovarian Cancer Study. NEC=New England Case-Control Study of Ovarian Cancer. UCI=University of California, Irvine Ovarian Cancer Study. USC=University of Southern California, Study of Lifestyle and Women's Health., OR=odds ratio.