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

Celeste Leigh Pearce,Allan Jensen,Doerthe Brueggmann,Andrew Berchuck,Argyrios Ziogas,Rebecca Hein,Usha Menon,Mary Anne Rossing,Claire Templeman,Galina Lurie,Hoda Anton‐Culver ,Rachel T Palmieri ,Lynne R Wilkens ,Susan J Ramus ,Kristine G Wicklund ,Harvey A Risch ,Daniel W Cramer ,August Anderson ,Anna H Wu ,Marc T Goodman ,Kara L Cushing‐Haugen ,Joellen M Schildkraut ,Estrid Høgdall ,Allison F Vitonis ,Kathryn L Terry ,Christina M Nagle ,Ellen L Goode ,Aimee M Near ,Alice W Lee ,Roberta B Ness ,Susanne K Kjær ,David G Huntsman ,A Gentry-Maharaj ,Simon A Gayther ,Brooke L Fridley ,Wendy R Brewster ,Peter A Fasching ,Penelope M Webb ,Jenny Chang‐Claude ,Michael E Carney ,Malcolm C Pike ,Melissa C Larson ,Jennifer A Doherty ,Kirsten B Moysich ,Linda Titus

doi:10.1016/s1470-2045(11)70404-1

Abstract

SummaryBackgroundEndometriosis 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.MethodsData 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.Findings13 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).InterpretationClinicians 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.FundingOvarian 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.

Highlights

Endometriosis is a common gynaecological disorder that is characterised by ectopic growth of endometrial glands and stroma
738 (9·3%) of 7911 women with invasive epithelial ovarian cancer and 168 (8·8%) of 1907 with borderline ovarian cancer reported a history of endometriosis. 818 (6·2%) of 13 226 controls reported a history of endometriosis
A history of endometriosis was reported by 136 (20·2%) of 674 women with clear-cell, 169 (13·9%) of 1220 with endometrioid, 31 (6·0%) of 516 with mucinous, 261 (7·1%) of 3659 with high-grade serous, and 31 (9·2%) of 336 with low-grade serous subtypes of invasive ovarian cancer. 103 (9·0%) of 1140 women with borderline serous and 65 (8·5%) of 767 with borderline mucinous tumours reported a history of endometriosis

Summary

Introduction

Endometriosis is a common gynaecological disorder that is characterised by ectopic growth of endometrial glands and stroma. The estimated prevalence in the general population, based on women undergoing tubal ligation, is about 4%; the disease is much more common in women with pelvic pain or infertility.[1] The disease process typically involves the surface of the ovaries and pelvic peritoneum and is commonly thought to be due to reflux of endometrial tissue through the fallopian tubes during menstruation. Endometriosis might cause pelvic inflammation, adhesions, chronic pain, and infertility, though such sequelae generally subside after menopause because growth of endometriotic tissue is oestrogen dependent.[2] An altered immune response is proposed to play a part in endometriosis.[3] Generally, the results of epidemiological studies have consistently shown that endometriosis is associated with an increase in risk of invasive epithelial ovarian cancer, the most fatal malignancy of the female reproductive system.[4,5,6,7,8,9,10,11,12,13,14]

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