The Association of Endometriosis with Ovarian Cancer: A Critical Review of Epidemiological Data

Although endometriosis is well recognized as a benign gynecologic condition, its association with ovarian cancer has frequently been reported. Many review papers on this topic have been published, yet there seems to be no consensus as to whether or not endometriosis is a precursor of ovarian cancer and whether or not any actions should be taken based on our current knowledge on the endometriosis-ovarian cancer association. In this chapter, I shall critically review epidemiological and clinical prevalence data for and against the link, point out the challenges in proving the causal link, and, in the end, sketch some ways to solve this problem. I shall provide a tutorial review of epidemiological studies, measures of effect size, and confounding and point out the connection between the prevalence data and the relative risk estimate. Funnel plots are used to examine the asymmetry of risk estimates, in which the risk estimates such as OR are plotted on a logarithmic scale against the inverse of their corresponding measures of precision. Areas in need of further research are also outlined. Access this chapter Tax calculation will be finalised at checkout Purchases are for personal use only Similar content being viewed by others

Sayasneh A, Tsivos D, Crawford R. Endometriosis and ovarian cancer: a systematic review. ISRN Obstet Gynecol. 2011;2011:140310. doi:10.5402/2011/140310. Kobayashi H, Kajiwara H, Kanayama S, Yamada Y, Furukawa N, Noguchi T, Haruta S, Yoshida S, Sakata M, Sado T, Oi H. Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (review). Oncol Rep. 2009;22(2):233–40. Hill AB. The environment and disease: association or causation? Proc R Soc Med. 1965;58:295–300. Vigano P, Somigliana E, Parazzini F, Vercellini P. Bias versus causality: interpreting recent evidence of association between endometriosis and ovarian cancer. Fertil Steril. 2007;88(3):588–93. Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM, Nagle CM, Doherty JA, Cushing-Haugen KL, Wicklund KG, Chang-Claude J, Hein R, Lurie G, Wilkens LR, Carney ME, Goodman MT, Moysich K, Kjaer SK, Hogdall E, Jensen A, Goode EL, Fridley BL, Larson MC, Schildkraut JM, Palmieri RT, Cramer DW, Terry KL, Vitonis AF, Titus LJ, Ziogas A, Brewster W, Anton-Culver H, Gentry-Maharaj A, Ramus SJ, Anderson AR, Brueggmann D, Fasching PA, Gayther SA, Huntsman DG, Menon U, Ness RB, Pike MC, Risch H, Wu AH, Berchuck A. Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol. 2012;13(4):385–94. Godwin AK, Testa JR, Hamilton TC. The biology of ovarian cancer development. Cancer. 1993;71(2 Suppl):530–6. Vaughan S, Coward JI, Bast Jr RC, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, Friedlander M, Gabra H, Kaye SB, Lord CJ, Lengyel E, Levine DA, McNeish IA, Menon U, Mills GB, Nephew KP, Oza AM, Sood AK, Stronach EA, Walczak H, Bowtell DD, Balkwill FR. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011;11(10):719–25. doi:10.1038/nrc3144. Light R, Pilleman DB. Summing up. The science of reviewing research. Cambridge: Harvard University Press; 1984. Team RDC. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna; 2009 (ISBN 3-900051-07-0, http://www.R-project.org.). Sampson JA. Endometrial carcinoma of the ovary arising in endometrial tissue in that organ. Arch Surg. 1925;10(1–72). Scott RB. Malignant changes in endometriosis. Obstet Gynecol. 1953;2(3):283–9. Somigliana E, Vigano P, Parazzini F, Stoppelli S, Giambattista E, Vercellini P. Association between endometriosis and cancer: a comprehensive review and a critical analysis of clinical and epidemiological evidence. Gynecol Oncol. 2006;101(2):331–41. Kurman RJ, Shih Ie M. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer–shifting the paradigm. Hum Pathol. 2011;42(7):918–31. Network TCGA. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70. Aure JC, Hoeg K, Kolstad P. Carcinoma of the ovary and endometriosis. Acta Obstet Gynecol Scand. 1971;50(1):63–7. Kurman RJ, Craig JM. Endometrioid and clear cell carcinoma of the ovary. Cancer. 1972;29(6):1653–64. Russell P. The pathological assessment of ovarian neoplasms. I: Introduction to the common ‘epithelial’ tumours and analysis of benign ‘epithelial’ tumours. Pathology. 1979;11(1):5–26. Brescia RJ, Dubin N, Demopoulos RI. Endometrioid and clear cell carcinoma of the ovary. Factors affecting survival. Int J Gynecol Pathol. 1989;8(2):132–8. Vercellini P, Parazzini F, Bolis G, Carinelli S, Dindelli M, Vendola N, Luchini L, Crosignani PG. Endometriosis and ovarian cancer. Am J Obstet Gynecol. 1993;169(1):181–2. Jimbo H, Yoshikawa H, Onda T, Yasugi T, Sakamoto A, Taketani Y. Prevalence of ovarian endometriosis in epithelial ovarian cancer. Int J Gynaecol Obstet. 1997;59(3):245–50. Fukunaga M, Nomura K, Ishikawa E, Ushigome S. Ovarian atypical endometriosis: its close association with malignant epithelial tumours. Histopathology. 1997;30(3):249–55. Ogawa S, Kaku T, Amada S, Kobayashi H, Hirakawa T, Ariyoshi K, Kamura T, Nakano H. Ovarian endometriosis associated with ovarian carcinoma: a clinicopathological and immunohistochemical study. Gynecol Oncol. 2000;77(2):298–304. Vercellini P, Scarfone G, Bolis G, Stellato G, Carinelli S, Crosignani PG. Site of origin of epithelial ovarian cancer: the endometriosis connection. BJOG. 2000;107(9):1155–7. Oral E, Ilvan S, Tustas E, Korbeyli B, Bese T, Demirkiran F, Arvas M, Kosebay D. Prevalence of endometriosis in malignant epithelial ovary tumours. Eur J Obstet Gynecol Reprod Biol. 2003;109(1):97–101. Dzatic-Smiljkovic O, Vasiljevic M, Djukic M, Vugdelic R, Vugdelic J. Frequency of ovarian endometriosis in epithelial ovarian cancer patients. Clin Exp Obstet Gynecol. 2011;38(4):394–8. Kondi-Pafiti A, Papakonstantinou E, Iavazzo C, Grigoriadis C, Salakos N, Gregoriou O. Clinicopathological characteristics of ovarian carcinomas associated with endometriosis. Arch Gynecol Obstet. 2012;285(2):479–83. Brinton LA, Gridley G, Persson I, Baron J, Bergqvist A. Cancer risk after a hospital discharge diagnosis of endometriosis. Am J Obstet Gynecol. 1997;176(3):572–9. Olson JE, Cerhan JR, Janney CA, Anderson KE, Vachon CM, Sellers TA. Postmenopausal cancer risk after self-reported endometriosis diagnosis in the Iowa Women’s Health Study. Cancer. 2002;94(5):1612–8. Brinton LA, Lamb EJ, Moghissi KS, Scoccia B, Althuis MD, Mabie JE, Westhoff CL. Ovarian cancer risk associated with varying causes of infertility. Fertil Steril. 2004;82(2):405–14. Brinton LA, Sakoda LC, Sherman ME, Frederiksen K, Kjaer SK, Graubard BI, Olsen JH, Mellemkjaer L. Relationship of benign gynecologic diseases to subsequent risk of ovarian and uterine tumors. Cancer Epidemiol Biomarkers Prev. 2005;14(12):2929–35. Melin A, Sparen P, Persson I, Bergqvist A. Endometriosis and the risk of cancer with special emphasis on ovarian cancer. Hum Reprod. 2006;21(5):1237–42. Murta EF, Nomelini RS, Ferreira FA, Lima MA. Ovarian clear cell carcinoma associated with endometriosis: a case report with immunohistochemical study. Eur J Gynaecol Oncol. 2007;28(5):403–5. Kobayashi H, Sumimoto K, Moniwa N, Imai M, Takakura K, Kuromaki T, Morioka E, Arisawa K, Terao T. Risk of developing ovarian cancer among women with ovarian endometrioma: a cohort study in Shizuoka, Japan. Int J Gynecol Cancer. 2007;17(1):37–43. Aris A. Endometriosis-associated ovarian cancer: a ten-year cohort study of women living in the Estrie Region of Quebec, Canada. J Ovarian Res. 2010;3:2. Stewart LM, Holman CD, Aboagye-Sarfo P, Finn JC, Preen DB, Hart R. In vitro fertilization, endometriosis, nulliparity and ovarian cancer risk. Gynecol Oncol. 2013;128:260–4 Sterne JAC, Egger M, Smith GD. Investigating and dealing with publication and other biases. In: Egger M, Smith GD, Altman DG, editors. Systematic reviews in Health Care: meta-analysis in context. London: BMJ Books; 2001. p. 189–208. Breslow NE, Day NE. Statistical methods in cancer research. vol. 1: The analysis of case-control studies. Lyon: IARC Scientific Publications No. 32. International Agency for Research on Cancer; 1980. Herbst AL, Ulfelder H, Poskanzer DC. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. 1971;284(15):878–81. doi:10.1056/NEJM197104222841604. Casagrande JT, Louie EW, Pike MC, Roy S, Ross RK, Henderson BE. “Incessant ovulation” and ovarian cancer. Lancet. 1979;2(8135):170–3. Vercellini P, Crosignani P, Somigliana E, Vigano P, Buggio L, Bolis G, Fedele L. The ‘incessant menstruation’ hypothesis: a mechanistic ovarian cancer model with implications for prevention. Hum Reprod. 2011;26(9):2262–73. Risch HA. Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst. 1998;90(23):1774–86. Cottreau CM, Ness RB, Modugno F, Allen GO, Goodman MT. Endometriosis and its treatment with danazol or lupron in relation to ovarian cancer. Clin Cancer Res. 2003;9(14):5142–4. Rothman KJ, Poole C. A strengthening programme for weak associations. Int J Epidemiol. 1988;17(4):955–9. Ness RB, Grisso JA, Cottreau C, Klapper J, Vergona R, Wheeler JE, Morgan M, Schlesselman JJ. Factors related to inflammation of the ovarian epithelium and risk of ovarian cancer. Epidemiology. 2000;11(2):111–7. Ness RB, Cramer DW, Goodman MT, Kjaer SK, Mallin K, Mosgaard BJ, Purdie DM, Risch HA, Vergona R, Wu AH. Infertility, fertility drugs, and ovarian cancer: a pooled analysis of case-control studies. Am J Epidemiol. 2002;155(3):217–24. Modugno F, Ness RB, Allen GO, Schildkraut JM, Davis FG, Goodman MT. Oral contraceptive use, reproductive history, and risk of epithelial ovarian cancer in women with and without endometriosis. Am J Obstet Gynecol. 2004;191(3):733–40. Borgfeldt C, Andolf E. Cancer risk after hospital discharge diagnosis of benign ovarian cysts and endometriosis. Acta Obstet Gynecol Scand. 2004;83(4):395–400. Merritt MA, Green AC, Nagle CM, Webb PM. Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer. Int J Cancer. 2008;122(1):170–6. doi:10.1002/ijc.23017. Nagle CM, Olsen CM, Webb PM, Jordan SJ, Whiteman DC, Green AC. Endometrioid and clear cell ovarian cancers: a comparative analysis of risk factors. Eur J Cancer. 2008;44(16):2477–84. Rossing MA, Cushing-Haugen KL, Wicklund KG, Doherty JA, Weiss NS. Risk of epithelial ovarian cancer in relation to benign ovarian conditions and ovarian surgery. Cancer Causes Control. 2008;19(10):1357–64. Wu AH, Pearce CL, Tseng CC, Templeman C, Pike MC. Markers of inflammation and risk of ovarian cancer in Los Angeles County. Int J Cancer. 2009;124(6):1409–15. Merritt MA, De Pari M, Vitonis AF, Titus LJ, Cramer DW, Terry KL. Reproductive characteristics in relation to ovarian cancer risk by histologic pathways. Hum Reprod. 28(5):1406–17. Melin AS, Lundholm C, Malki N, Swahn ML, Sparen P, Bergqvist A. Hormonal and surgical treatments for endometriosis and risk of epithelial ovarian cancer. Acta Obstet Gynecol Scand. 2013;92(5):546–54. doi:10.1111/aogs.12123. Kuhn E, Kurman RJ, Shih IM. Ovarian cancer is an imported disease: fact or fiction? Curr Obstet Gynecol Rep. 2012;1(1):1–9. Baldi A, Campioni M, Signorile PG. Endometriosis: pathogenesis, diagnosis, therapy and association with cancer (review). Oncol Rep. 2008;19(4):843–6. Erzen M, Rakar S, Klancnik B, Syrjanen K. Endometriosis-associated ovarian carcinoma (EAOC): an entity distinct from other ovarian carcinomas as suggested by a nested case-control study. Gynecol Oncol. 2001;83(1):100–8. Wang S, Qiu L, Lang JH, Shen K, Huang HF, Pan LY, Wu M, Yang JX, Guo LN. Prognostic analysis of endometrioid epithelial ovarian cancer with or without endometriosis: a 12-year cohort study of Chinese patients. Am J Obstet Gynecol. 2013;209:241. Melin A, Lundholm C, Malki N, Swahn ML, Sparen P, Bergqvist A. Endometriosis as a prognostic factor for cancer survival. Int J Cancer. 2011;129(4):948–55. doi:10.1002/ijc.25718. Cuff J, Longacre TA. Endometriosis does not confer improved prognosis in ovarian carcinoma of uniform cell type. Am J Surg Pathol. 2012;36(5):688–95. Noli S, Cipriani S, Scarfone G, Villa A, Grossi E, Monti E, Vercellini P, Parazzini F. Long term survival of ovarian endometriosis associated clear cell and endometrioid ovarian cancers. Int J Gynecol Cancer. 2013. Wu Y, Basir Z, Kajdacsy-Balla A, Strawn E, Macias V, Montgomery K, Guo SW. Resolution of clonal origins for endometriotic lesions using laser capture microdissection and the human androgen receptor (HUMARA) assay. Fertil Steril. 2003;79 Suppl 1:710–7. Wu Y, Guo SW. Reconstructing cellular lineages in endometrial cells. Fertil Steril. 2008;89(2):481–4. doi:10.1016/j.fertnstert.2007.03.028. Acknowledgment I would like to thank Professor Paolo Vercellini for stimulating the discussion when preparing for this chapter. This research was supported in part by grant 81270676 from the National Science Foundation of China and financial support from Fudan University and the Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases. Conflict of Interest Statement None declared. Author information Authors and Affiliations Corresponding author Editor information Editors and Affiliations Rights and permissions Copyright information © 2014 Springer Japan About this chapter Cite this chapter Guo, SW. (2014). The Association of Endometriosis with Ovarian Cancer: A Critical Review of Epidemiological Data. In: Harada, T. (eds) Endometriosis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54421-0_22 Download citation DOI: https://doi.org/10.1007/978-4-431-54421-0_22 Published: Publisher Name: Springer, Tokyo Print ISBN: 978-4-431-54420-3 Online ISBN: 978-4-431-54421-0 eBook Packages: MedicineMedicine (R0)