Endometriosis is associated with ovarian cancer, but the relation with endometrial cancer is unclear. Prior studies generally were retrospective and had potential limitations, including use of self-reported endometriosis, failure to account for delays between symptom onset and endometriosis diagnosis, and changes in risk factors post-endometriosis diagnosis. We evaluated whether these limitations obscured a weak association with endometrial cancer and the extent to which these limitations impacted associations with ovarian cancer.
Cox proportional hazards regression models were used to assess associations between endometriosis and cancer risk, evaluating the impacts of self-reported vs. laparoscopically confirmed endometriosis, delayed diagnosis, and post-endometriosis diagnosis changes in risk factor exposures on relative risk estimates.
Over 18 years of follow-up, we identified 228 ovarian and 166 endometrial cancers among 102,025 and 97,109 eligible women, respectively. Self-reported endometriosis was associated with ovarian cancer [relative risk (RR): 1.81; 95% confidence interval (CI): 1.26–2.58]; this association was stronger for laparoscopically confirmed endometriosis (HR: 2.14; 95% CI 1.45–3.15). No association was observed with endometrial cancer (self-report RR: 0.78; 95% CI 0.42–1.44; laparoscopic-confirmation RR: 0.76; 95% CI 0.35–1.64). Accounting for diagnosis delays or post-endometriosis diagnosis changes in risk factors had a little impact.
This study adds to the evidence that endometriosis is not strongly linked to endometrial cancer risk and that the association with ovarian cancer is robust to misclassification, diagnostic delay, and changes in exposures post-endometriosis diagnosis. Our analysis suggests that confounding and misclassification do not obscure a weak association for endometrial cancer risk, although our results should be replicated.
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Giudice LC (2010) Clinical practice. Endometriosis. N Engl J Med 362:2389–2398
Burney RO, Giudice LC (2012) Pathogenesis and pathophysiology of endometriosis. Fertil Steril 98:511–519
Missmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Marshall LM, Hunter DJ (2004) Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors. Am J Epidemiol 160:784–796
Brinton LA, Westhoff CL, Scoccia B et al (2005) Causes of infertility as predictors of subsequent cancer risk. Epidemiology 16:500–507
Brinton LA, Sakoda LC, Sherman ME et al (2005) Relationship of benign gynecologic diseases to subsequent risk of ovarian and uterine tumors. Cancer epidemiology, biomarkers and prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive. Int Soc Cell 14:2929–2935
Kobayashi H, Sumimoto K, Moniwa N et al (2007) Risk of developing ovarian cancer among women with ovarian endometrioma: a cohort study in Shizuoka, Japan. Int J Gynecol Cancer 17:37–43
Pearce CL, Templeman C, Rossing MA et al (2012) Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies. Lancet Oncol 13:385–394
Buis CC, van Leeuwen FE, Mooij TM, Burger CW, Group OP (2013) Increased risk for ovarian cancer and borderline ovarian tumours in subfertile women with endometriosis. Hum Reprod 28:3358–3369
Kvaskoff M, Mu F, Terry KL et al (2015) Endometriosis: a high-risk population for major chronic diseases? Hum Reprod Update 21(4):500–516
Lee WL, Chang WH, Wang KC et al (2015) The risk of epithelial ovarian cancer of women with endometriosis may be varied greatly if diagnostic criteria are different: a nationwide population-based cohort study. Medicine (Baltimore) 94:e1633
Mogensen JB, Kjaer SK, Mellemkjaer L, Jensen A (2016) Endometriosis and risks for ovarian, endometrial and breast cancers: a nationwide cohort study. Gynecol Oncol 143:87–92
de Boer EJ, den Tonkelaar I, Burger CW, van Leeuwen FE, Group OP (2005) Validity of self-reported causes of subfertility. Am J Epidemiol 161:978–986
Nnoaham KE, Hummelshoj L, Webster P et al (2011) Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril 96(366–73):e8
Borgfeldt C, Andolf E (2004) Cancer risk after hospital discharge diagnosis of benign ovarian cysts and endometriosis. Acta Obstet Gynecol Scand 83:395–400
Brinton LA, Gridley G, Persson I, Baron J, Bergqvist A (1997) Cancer risk after a hospital discharge diagnosis of endometriosis. Am J Obstet Gynecol 176:572–579
Melin A, Sparen P, Persson I, Bergqvist A (2006) Endometriosis and the risk of cancer with special emphasis on ovarian cancer. Hum Reprod 21:1237–1242
Munksgaard PS, Blaakaer J (2011) The association between endometriosis and gynecological cancers and breast cancer: a review of epidemiological data. Gynecol Oncol 123:157–163
Rowlands IJ, Nagle CM, Spurdle AB, Webb PM, Australian National Endometrial Cancer Study G, Australian Ovarian Cancer Study G (2011) Gynecological conditions and the risk of endometrial cancer. Gynecol Oncol 123: 537–541
Zucchetto A, Serraino D, Polesel J et al (2009) Hormone-related factors and gynecological conditions in relation to endometrial cancer risk. Eur J Cancer Prev Off J Eur Cancer Prev Organ 18:316–321
Kurman RJ, Shih Ie M (2011) Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer–shifting the paradigm. Hum Pathol 42:918–931
McConechy MK, Anglesio MS, Kalloger SE et al (2011) Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas. J Pathol 223:567–573
McConechy MK, Ding J, Senz J et al (2014) Ovarian and endometrial endometrioid carcinomas have distinct CTNNB1 and PTEN mutation profiles. Mod Pathol 27:128–134
Rockhill B, Willett WC, Hunter DJ et al (1998) Physical activity and breast cancer risk in a cohort of young women. J Natl Cancer Inst 90:1155–1160
Hosmer DW, Lemeshow S (1999) Applied survival analysis: regression modeling of time to event data. Wiley, New York
Olson JE, Cerhan JR, Janney CA, Anderson KE, Vachon CM, Sellers TA (2002) Postmenopausal cancer risk after self-reported endometriosis diagnosis in the Iowa Women’s Health Study. Cancer 94:1612–1618
Melin A, Sparen P, Bergqvist A (2007) The risk of cancer and the role of parity among women with endometriosis. Hum Reprod 22:3021–3026
Venn A, Watson L, Bruinsma F, Giles G, Healy D (1999) Risk of cancer after use of fertility drugs with in-vitro fertilisation. Lancet 354:1586–1590
Kim JJ, Kurita T, Bulun SE (2013) Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer. Endocr Rev 34:130–162
Ness RB (2003) Endometriosis and ovarian cancer: thoughts on shared pathophysiology. Am J Obstet Gynecol 189:280–294
Nezhat F, Datta MS, Hanson V, Pejovic T, Nezhat C, Nezhat C (2008) The relationship of endometriosis and ovarian malignancy: a review. Fertil Steril 90:1559–1570
Maccio A, Madeddu C (2012) Inflammation and ovarian cancer. Cytokine 58:133–147
Lee AW, Templeman C, Stram DA et al (2015) Evidence of a genetic link between endometriosis and ovarian cancer. Fertil Steril 105(1):35–43
Lu Y, Cuellar-Partida G, Painter JN et al (2015) Shared genetics underlying epidemiological association between endometriosis and ovarian cancer. Hum Mol Genet 24:5955–5964
Sato N, Tsunoda H, Nishida M et al (2000) Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary. Cancer Res 60:7052–7056
Dinulescu DM, Ince TA, Quade BJ, Shafer SA, Crowley D, Jacks T (2005) Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med 11:63–70
Wiegand KC, Shah SP, Al-Agha OM et al (2010) ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med 363:1532–1543
Holt VL, Weiss NS (2000) Recommendations for the design of epidemiologic studies of endometriosis. Epidemiology 11:654–659
Felix AS, Weissfeld JL, Stone RA et al (2010) Factors associated with type I and type II endometrial cancer. Cancer Causes Control 21:1851–1856
Brasky TM, Felix AS, Cohn DE et al (2017) Nonsteroidal anti-inflammatory drugs and endometrial carcinoma mortality and recurrence. J Natl Cancer Inst 109(3):djw251. doi:10.1093/jnci/djw251
Brinton LA, Felix AS, McMeekin DS et al (2013) Etiologic heterogeneity in endometrial cancer: evidence from a Gynecologic Oncology Group trial. Gynecol Oncol 129:277–284
Brinton LA, Trabert B, Anderson GL et al (2016) Serum estrogens and estrogen metabolites and endometrial cancer risk among postmenopausal women. Cancer epidemiology, biomarkers and prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive. Int Soc Cell 25:1081–1089
Setiawan VW, Yang HP, Pike MC et al (2013) Type I and II endometrial cancers: have they different risk factors? J Clin Oncol 31:2607–2618
Uccella S, Mariani A, Wang AH et al (2013) Intake of coffee, caffeine and other methylxanthines and risk of type I vs type II endometrial cancer. Br J Cancer 109:1908–1913
The authors wish to thank the participants and staff of the Nurses’ Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. This work was supported by the National Institutes of Health (R01 HD57210, UM1 CA176726) and Dana Farber Cancer Institute Mazzone Award.
This work was supported by the National Institutes of Health (R01 HD57210, UM1 CA176726) and Dana Farber Cancer Institute Mazzone Award.
Conflict of interest
The authors declare that they have no financial or personal relationships that might influence this work.
E. M. Poole and W. T. Lin contributed equally to this work.
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Poole, E.M., Lin, W.T., Kvaskoff, M. et al. Endometriosis and risk of ovarian and endometrial cancers in a large prospective cohort of U.S. nurses. Cancer Causes Control 28, 437–445 (2017). https://doi.org/10.1007/s10552-017-0856-4