Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies
Open accessAbstract
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.
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Self-reported endometriosis is associated with significantly increased risk for endometrioid cancer (OR 2.21).
“endometrioid cancer (OR 2.21)”
From Clear cell carcinoma arising from abdominal wall endometriosis – Brief report and review of the literature (2017) · cites this paper as Pearce et al. (2012)
Epigenetics and genomic instability associated with the particular microenvironment of endometriosis, characterized by oxidative stress, inflammatory process and high estrogen levels, contribute to the process of malignant transformation of endometriosis.
“It is becoming clear that epigenetics and genomic instability associated with the particular microenvironment of endometriosis characterized by oxidative stress, inflammatory process and high estrogen levels contribute to the process of malignant transformation of endometriosis (Pearce et al., 2012, Nezhat et al., 2014).”
From Clear cell carcinoma arising from abdominal wall endometriosis – Brief report and review of the literature (2017) · cites this paper as Pearce et al., 2012
Self-reported endometriosis is associated with significantly increased risk for low-grade serous invasive ovarian cancers (OR 2.21).
“and low-grade serous invasive ovarian cancers (OR 2.21).”
From Clear cell carcinoma arising from abdominal wall endometriosis – Brief report and review of the literature (2017) · cites this paper as Pearce et al. (2012)
Self-reported endometriosis is associated with significantly increased risk for clear cell carcinoma (OR 3.05).
“Pearce et al. (2012), concluded that self-reported endometriosis was associated with significantly increased risk for CCC [odds ratio (OR) 3.05]”
From Clear cell carcinoma arising from abdominal wall endometriosis – Brief report and review of the literature (2017) · cites this paper as Pearce et al. (2012)
Pearce et al. summarized 13 case-control studies and reported the highest odds ratio of 3.05 for clear cell carcinoma, followed by LG-serous (2.11) and endometrioid carcinoma (2.04) in patients with endometriosis.
“Pearce et al. summarized 13 case-control studies and reported the highest odds ratio of 3.05 for clear cell carcinoma, followed by LG-serous (2.11) and endometrioid carcinoma (2.04) in patients with endometriosis [9].”
From Malignancies Associated with Extraovarian Endometriosis: A Literature Review (2021) · cites this paper as [9]
Malignant transformation of ovarian endometriosis has been well documented.
“Malignant transformation of ovarian endometriosis has been well documented.”
From Malignancies Associated with Extraovarian Endometriosis: A Literature Review (2021) · cites this paper as [9]
In population-based studies, the incidence of ovarian cancer in patients with a history of ovarian endometriosis is 1.35-1.49 times greater compared with those without this history.
“In population-based studies, the incidence of ovarian cancer in patients with a history of ovarian endometriosis is 1.35-1.49times greater compared with those without this history [9,10].”
From Malignancies Associated with Extraovarian Endometriosis: A Literature Review (2021) · cites this paper as [9]
Of the 19 SNPs and high-LD proxies, associations were observed with multiple diseases or traits, including epithelial ovarian cancer, low-density lipoprotein cholesterol, coronary heart disease, luteinizing hormone and follicle-stimulating hormone levels, and age at onset for menopause.
“Of these, we observed associations with multiple diseases or traits, including epithelial ovarian cancer21, low-density lipoprotein cholesterol22, coronary heart disease23, luteinizing hormone and follicle-stimulating hormone levels, and age at onset for menopause24.”
From Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism (2017) · cites this paper as [21]
In a study of 13,226 controls and 7,911 women with invasive ovarian cancer, self-reported endometriosis was associated with a significantly increased risk of clear-cell, low-grade serous, and endometrioid invasive ovarian cancers.
“Most recently, in a study of 13 226 controls and 7911 women with invasive ovarian cancer, self-reported endometriosis was associated with a significantly increased risk of clear-cell, low-grade serous, and endometrioid invasive ovarian cancers.”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [118]
No association was noted between endometriosis and risk of mucinous or high-grade serous invasive ovarian cancer or borderline tumors of either subtype.
“No association was noted between endometriosis and risk of mucinous or high-grade serous invasive ovarian cancer or borderline tumors of either subtype.118”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [118]
Endometriosis and ovarian cancer have been linked by a number of studies.
“Endometriosis and ovarian cancer have been linked by a number of studies.”
From Defining Future Directions for Endometriosis Research: Workshop Report From the 2011 World Congress of Endometriosis in Montpellier, France (2013) · cites this paper as [118]
These medical conditions have been (suggested to be) associated with endometriosis or its constituting symptoms in epidemiologic studies.
“which have been (suggested to be) associated with endometriosis or its constituting symptoms in epidemiologic studies (51–54).”
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Self-citation
- Authors
- Pearce, C. L., Templeman, C., Rossing, M. A., Lee, A., Near, A. M., Webb, P. M., Nagle, C. M., Doherty, J. A., Cushing-Haugen, K. L., Wicklund, K. G., Chang-Claude, J., Hein, R., Lurie, G., Wilkens, L. R., Carney, M. E., Goodman, M. T., Moysich, K., Kjaer, S. K., Hogdall, E., Jensen, A., Goode, E. L., Fridley, B. L., Larson, M. C., Schildkraut, J. M., Palmieri, R. T., Cramer, D. W., Terry, K. L., Vitonis, A. F., Titus, L. J., Ziogas, A., Brewster, W., Anton-Culver, H., Gentry-Maharaj, A., Ramus, S. J., Anderson, A. R., Brueggmann, D., Fasching, P. A., Gayther, S. A., Huntsman, D. G., Menon, U., Ness, R. B., Pike, M. C., Risch, H., Wu, A. H., & Berchuck, A.
- Affiliations
- University of Southern California (US)
- Fred Hutch Cancer Center (US)
- Georgetown University Medical Center (US)
- QIMR Berghofer Medical Research Institute (AU)
- German Cancer Research Center (DE)
- University of Hawaiʻi at Mānoa (US)
- Roswell Park Comprehensive Cancer Center (US)
- Danish Cancer Society (DK)
- Mayo Clinic (US)
- Duke Medical Center (US)
- Brigham and Women's Hospital (US)
- Dartmouth College (US)
- University of California, Irvine (US)
- University of North Carolina at Chapel Hill (US)
- University College London (GB)
- University of California, Los Angeles (US)
- Yale University (US)
- Corresponding author
- Pearce, Celeste Leigh
- ORCID
- Pearce, Celeste Leigh
- Lee, Alice
- Near, Aimee M
- Webb, Penelope M
- Nagle, Christina M
- Doherty, Jennifer A
- Wicklund, Kristine G
- Wilkens, Lynne R
- Goodman, Marc T
- Moysich, Kirsten
- Jensen, Allan
- Goode, Ellen L
- Fridley, Brooke L
- Larson, Melissa C
- Schildkraut, Joellen M
- Cramer, Daniel W
- Terry, Kathryn L
- Titus, Linda J
- Ziogas, Argyrios
- Brewster, Wendy
- Ramus, Susan J
- Fasching, Peter A
- Gayther, Simon A
- Menon, Usha
- Pike, Malcolm C
- Risch, Harvey
- Wu, Anna H
- Berchuck, Andrew
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 13
- Issue
- 4
- Pages
- 385-394
- ISSN
- 1470-2045 (ISSN-L)
- PMC
- PMC3664011
- OpenAlex
- W2125681453
- Cited by
- 939
- References
- 43
- Citations by year
- 2026: 47 · 2025: 53 · 2024: 46 · 2023: 64 · 2022: 44 · 2021: 84 · 2020: 88 · 2019: 77 · 2018: 71 · 2017: 83 · 2016: 68 · 2015: 65 · 2014: 55 · 2013: 68 · 2012: 26
- FWCI
- 79.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Lancet Oncology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- California Breast Cancer Research Program (0001389V20170, 2110200)
- Seventh Framework Programme (HEALTH-F2-2009-223175)
- University of South China
- National Institutes of Health (5R01 CA074850, CA14089, CA17054, CA58860, CA61132, CA92044, N01 CN67001, N01 PC35137, N01 PC67010, P50 CA105009, P50 CA136393, PSA 042205, R01 CA112523, R01 CA122443, R01 CA126841, R01 CA136891, R01 CA54419, R01 CA58598, R01 CA61107, R01 CA76016, R01 CA87538, R01 CA95023, R03 CA113148)
- Medical Research and Materiel Command (DAMD 170110729, DAMD17-02-1-0669, W81XWH0610220, W81XWH1010280)
- Oak Foundation
- Lon V. Smith Foundation (LVS 39420)
- California Department of Public Health (050E8709)
- Roswell Park Alliance Foundation, Roswell Park Cancer Institute
- Kræftens Bekæmpelse
- Deutsches Krebsforschungszentrum
- National Health and Medical Research Council (199600)
- Cancer Council Tasmania
- American University of Sharjah
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Keywords
- endometriosis, ovarian cancer, histological subtypes, ovarian clear cell carcinoma, low-grade serous ovarian cancer, endometrioid ovarian cancer, mucinous ovarian carcinoma, high-grade serous ovarian cancer, borderline ovarian tumors, cancer risk factors, oral contraceptive use, parity, tumor stage and grade, Ovarian Cancer Association Consortium
- MeSH terms
- Aged, Aged, 80 and over, Endometriosis, Ethnicity, Female, Humans, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, Ovarian Neoplasms, Risk Factors, Case-Control Studies
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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