{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T13:44:17Z","timestamp":1782135857663,"version":"3.54.5"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,29]],"date-time":"2023-01-29T00:00:00Z","timestamp":1674950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chung Shan Medical University Hospital","award":["CSH-2019-C-002"],"award-info":[{"award-number":["CSH-2019-C-002"]}]},{"name":"Chung Shan Medical University Hospital","award":["CSH-2022-C-043"],"award-info":[{"award-number":["CSH-2022-C-043"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The relationship between uterine corpus cancer and endometriosis was conflicting. We aimed to determine the risk of uterine cancer in patients with endometriosis or pelvic inflammatory disease (PID). In this population-based cohort study, a total of 135,236 females with endometriosis (n = 20,510) or PID (n = 114,726), as well as 135,236 age-matched controls, were included. Cox regression models estimated the risk of uterine cancer in each group. Sub-outcomes of risk for uterine corpus cancer included endometrial cancer and uterine sarcoma were analyzed. An age subgroup analysis was performed to determine the moderator effect of age. A landmark analysis depicted the time varying effect of endometriosis and PID. A propensity score matching analysis was conducted to validate the findings. Patients with endometriosis had significantly higher risk of endometrial cancer (adjusted hazard ratio, aHR = 2.92; 95% CI = 2.12\u20134.03) and uterine sarcoma (aHR = 5.83; 95% CI = 2.02\u201316.89), while PID was not associated with the risk of uterine cancer. The increased risk of uterine cancer in patients with endometriosis persisted after propensity score matching (aHR = 2.83, 95%CI = 1.70\u20134.71). The greatest risk of endometrial cancer occurred in patients who had endometriosis for 37 to 60 months (adjusted relative risk, aRR = 9.15, 95% CI = 4.40\u201319.02). Females aged 12 to 35 years were at the greatest risk of endometriosis-associated uterine cancer (RR = 6.97, 95% CI = 3.41\u201314.26). In conclusion, patients with endometriosis were at great risk of uterine cancer, including endometrial cancer and uterine sarcoma, compared with propensity score-matched populations and compared with patients of PID. Younger females with endometriosis and patients who had endometriosis for three to five years were at the greatest risk of endometriosis-associated uterine cancer.<\/jats:p>","DOI":"10.3390\/cancers15030833","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T11:19:53Z","timestamp":1675077593000},"page":"833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Risk of Endometrial Cancer and Uterine Sarcoma Following Endometriosis or Pelvic Inflammatory Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Jing-Yang","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9394-4144","authenticated-orcid":false,"given":"Kevin Sheng-Kai","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"},{"name":"Center for Global Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Department of Dermatology, Massachusetts General Hospital, Boston, MA 02114, USA"},{"name":"Department of Orthodontics and Dentofacial Orthopedics, Henry M. Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Tzu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, National Taiwan University Hospital & College of Medicine, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cho-Han","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mount Auburn Hospital, Cambridge, MA 02138, USA"},{"name":"Harvard Medical School, Harvard University, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0365-7927","authenticated-orcid":false,"given":"Shun-Fa","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Taiwan University, Taipei 10617, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"},{"name":"School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1186\/s12967-020-02471-0","article-title":"Endometriosis: Current challenges in modeling a multifactorial disease of unknown etiology","volume":"18","author":"Malvezzi","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bpobgyn.2018.06.001","article-title":"Risk for and consequences of endometriosis: A critical epidemiologic review","volume":"51","author":"Shafrir","year":"2018","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.trsl.2021.12.002","article-title":"Repurposing gestrinone for tumor suppressor through P21 reduction regulated by JNK in gynecological cancer","volume":"243","author":"Ciou","year":"2022","journal-title":"Transl. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1093\/humupd\/dmt010","article-title":"Endometriosis: Hormone regulation and clinical consequences of chemotaxis and apoptosis","volume":"19","author":"Reis","year":"2013","journal-title":"Hum. Reprod. Update"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1080\/13510002.2019.1632603","article-title":"Increased systemic and peritoneal oxidative stress biomarkers in endometriosis are not related to retrograde menstruation","volume":"24","author":"Hicks","year":"2019","journal-title":"Redox Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1016\/j.humpath.2012.02.005","article-title":"Involvement of pelvic inflammation-related mismatch repair abnormalities and microsatellite instability in the malignant transformation of ovarian endometriosis","volume":"43","author":"Fuseya","year":"2012","journal-title":"Hum. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1056\/NEJMra1411426","article-title":"Pelvic inflammatory disease","volume":"372","author":"Brunham","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1097\/CEJ.0b013e328329d830","article-title":"Hormone-related factors and gynecological conditions in relation to endometrial cancer risk","volume":"18","author":"Zucchetto","year":"2009","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Marquardt, R.M., Kim, T.H., Shin, J.H., and Jeong, J.W. (2019). Progesterone and Estrogen Signaling in the Endometrium: What Goes Wrong in Endometriosis?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153822"},{"key":"ref_11","first-page":"854","article-title":"Nitric oxide and oxygen radicals in infection, inflammation, and cancer","volume":"63","author":"Maeda","year":"1998","journal-title":"Biochemistry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"149185","DOI":"10.1155\/2014\/149185","article-title":"Chronic inflammation and cytokines in the tumor microenvironment","volume":"2014","author":"Landskron","year":"2014","journal-title":"J. Immunol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.1158\/1055-9965.EPI-05-0493","article-title":"Inflammation and endometrial cancer: A hypothesis","volume":"14","author":"Modugno","year":"2005","journal-title":"Cancer Epidemiol. Biomarkers Prev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/431405a","article-title":"Cancer: An inflammatory link","volume":"431","author":"Balkwill","year":"2004","journal-title":"Nature"},{"key":"ref_15","unstructured":"Ministry of Health and Welfare (2020). Cancer Registry Annual Report, Taiwan, Ministry of Health and Welfare."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1136\/jmedgenet-2019-106529","article-title":"Association between genetic polymorphisms and endometrial cancer risk: A systematic review","volume":"57","author":"Bafligil","year":"2020","journal-title":"J. Med. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00404-017-4391-z","article-title":"Current strategies in the diagnosis of endometrial cancer","volume":"296","author":"Tzur","year":"2017","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ygyno.2016.07.095","article-title":"Endometriosis and risks for ovarian, endometrial and breast cancers: A nationwide cohort study","volume":"143","author":"Mogensen","year":"2016","journal-title":"Gynecol. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.ygyno.2011.08.022","article-title":"Gynecological conditions and the risk of endometrial cancer","volume":"123","author":"Rowlands","year":"2011","journal-title":"Gynecol. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1097\/IGC.0000000000000454","article-title":"The Risks for Ovarian, Endometrial, Breast, Colorectal, and Other Cancers in Women With Newly Diagnosed Endometriosis or Adenomyosis: A Population-Based Study","volume":"25","author":"Kok","year":"2015","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1111\/1471-0528.14793","article-title":"Impact of endometriosis on risk of further gynaecological surgery and cancer: A national cohort study","volume":"125","author":"Saraswat","year":"2018","journal-title":"BJOG"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1278","DOI":"10.1097\/MD.0000000000001278","article-title":"Risk of Endometrial Cancer in Women with Pelvic Inflammatory Disease: A Nationwide Population-Based Retrospective Cohort Study","volume":"94","author":"Yang","year":"2015","journal-title":"Medicine"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Shen, C.C., Hu, L.Y., Yang, A.C., Chiang, Y.Y., Hung, J.H., and Tsai, S.J. (2016). Risk of uterine, ovarian and breast cancer following pelvic inflammatory disease: A nationwide population-based retrospective cohort study. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2857-1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"217","DOI":"10.2307\/271011","article-title":"Event-history analysis for left-truncated data","volume":"23","author":"Guo","year":"1993","journal-title":"Sociol. Methodol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.15585\/mmwr.mm6748a1","article-title":"Uterine Cancer Incidence and Mortality-United States, 1999\u20132016","volume":"67","author":"Henley","year":"2018","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12982-017-0060-8","article-title":"On hazard ratio estimators by proportional hazards models in matched-pair cohort studies","volume":"14","author":"Shinozaki","year":"2017","journal-title":"Emerg. Themes Epidemiol."},{"key":"ref_27","first-page":"391","article-title":"Landmark analysis: A primer","volume":"26","author":"Morgan","year":"2019","journal-title":"J. Nucl. Cardiol. Off. Publ. Am. Soc. Nucl. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S2213-8587(17)30258-9","article-title":"Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic): A multinational observational analysis","volume":"5","author":"Birkeland","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"l1204","DOI":"10.1136\/bmj.l1204","article-title":"Incidence of type 2 diabetes mellitus in men receiving steroid 5alpha-reductase inhibitors: Population based cohort study","volume":"365","author":"Wei","year":"2019","journal-title":"BMJ"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s10552-017-0856-4","article-title":"Endometriosis and risk of ovarian and endometrial cancers in a large prospective cohort of U.S. nurses","volume":"28","author":"Poole","year":"2017","journal-title":"Cancer Causes Control"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1093\/humrep\/dem209","article-title":"The risk of cancer and the role of parity among women with endometriosis","volume":"22","author":"Melin","year":"2007","journal-title":"Hum. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00404-020-05445-1","article-title":"Association between endometriosis and gynecological cancers: A critical review of the literature","volume":"301","author":"Kalaitzopoulos","year":"2020","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1093\/humrep\/deq032","article-title":"Inflammatory cytokines differentially up-regulate human endometrial haptoglobin production in women with endometriosis","volume":"25","author":"Nabli","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1006\/smim.2000.0210","article-title":"The I kappa B kinase (IKK) and NF-kappa B: Key elements of proinflammatory signalling","volume":"12","author":"Karin","year":"2000","journal-title":"Semin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.3389\/fimmu.2020.01387","article-title":"The NF-kappaB Signaling Pathway, the Microbiota, and Gastrointestinal Tumorigenesis: Recent Advances","volume":"11","author":"Peng","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/aogs.13156","article-title":"Progesterone resistance in endometriosis: Origins, consequences and interventions","volume":"96","author":"Patel","year":"2017","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"68.e1","DOI":"10.1016\/j.ajog.2016.02.036","article-title":"The gut microbiota: A puppet master in the pathogenesis of endometriosis?","volume":"215","author":"Laschke","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s12672-019-0358-9","article-title":"Estrogen Signaling in Endometrial Cancer: A Key Oncogenic Pathway with Several Open Questions","volume":"10","author":"Rodriguez","year":"2019","journal-title":"Horm. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1002\/cam4.1445","article-title":"Genetic overlap between endometriosis and endometrial cancer: Evidence from cross-disease genetic correlation and GWAS meta-analyses","volume":"7","author":"Painter","year":"2018","journal-title":"Cancer Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Miku\u0161, M., Gold\u0161tajn, M., Brle\u010di\u0107, I., Duman\u010di\u0107, S., Lagan\u00e0, A.S., Chiantera, V., Vuji\u0107, G., and \u0106ori\u0107, M. (2022). CTLA4-Linked Autoimmunity in the Pathogenesis of Endometriosis and Related Infertility: A Systematic Review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810902"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/ijgo.13066","article-title":"Pelvic inflammatory disease and risk of cancer: A nationwide cohort study","volume":"149","author":"Leisner","year":"2020","journal-title":"Int. J. Gynaecol. Obstet. Off. Organ Int. Fed. Gynaecol. Obstet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1002\/cam4.2044","article-title":"Hormonal therapy in uterine sarcomas","volume":"8","author":"Zang","year":"2019","journal-title":"Cancer Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"125","DOI":"10.5603\/GP.a2018.0022","article-title":"HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR expression in infertile women with endometriosis","volume":"89","author":"Wirstlein","year":"2018","journal-title":"Ginekol. Pol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1055\/s-0036-1583293","article-title":"Common Dysregulated Genes in Endometriosis and Malignancies","volume":"38","author":"Dentillo","year":"2016","journal-title":"Rev. Bras. Ginecol. Obs."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Honda, H., Barrueto, F.F., Gogusev, J., Im, D.D., and Morin, P.J. (2008). Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis. Reprod. Biol. Endocrinol., 6.","DOI":"10.1186\/1477-7827-6-59"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1159\/000341706","article-title":"Endometrial stromal sarcoma arising from endometriosis: A clinicopathological study and literature review","volume":"74","author":"Lan","year":"2012","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.ijscr.2020.06.062","article-title":"Endometrial stromal sarcoma arising from polypoid endometriosis: Case report and literature review","volume":"72","author":"Carbone","year":"2020","journal-title":"Int. J. Surg. Case Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1093\/aje\/kwq481","article-title":"Bias due to left truncation and left censoring in longitudinal studies of developmental and disease processes","volume":"173","author":"Cain","year":"2011","journal-title":"Am. J. Epidemiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/S1470-2045(11)70165-6","article-title":"Risk of ovarian cancer in women with pelvic inflammatory disease: A population-based study","volume":"12","author":"Lin","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1200\/JCO.2012.48.2596","article-title":"Type I and II endometrial cancers: Have they different risk factors?","volume":"31","author":"Setiawan","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_51","first-page":"632","article-title":"Endometriosis, Pain and Mental Health","volume":"33","author":"Bjedov","year":"2021","journal-title":"Psychiatr. Danub."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2147\/CLEP.S196293","article-title":"Taiwan's National Health Insurance Research Database: Past and future","volume":"11","author":"Hsieh","year":"2019","journal-title":"Clin. Epidemiol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/3\/833\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:19:11Z","timestamp":1760120351000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/3\/833"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,29]]},"references-count":52,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["cancers15030833"],"URL":"https:\/\/doi.org\/10.3390\/cancers15030833","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,29]]}}}