{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T01:44:40Z","timestamp":1770342280405,"version":"3.49.0"},"reference-count":20,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2009,3,11]],"date-time":"2009-03-11T00:00:00Z","timestamp":1236729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health grant","doi-asserted-by":"crossref","award":["RO1-CA100833"],"award-info":[{"award-number":["RO1-CA100833"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NHRI Physician Scientist Award, Taiwan"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["K07 CA117979-01"],"award-info":[{"award-number":["K07 CA117979-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2009,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>Inactivation of the <jats:italic>PTEN<\/jats:italic> suppressor gene has been shown to occur in the majority of endometrial cancer cases. Somatic <jats:italic>PTEN<\/jats:italic> inactivation by deletion and\/or mutation, the first detectible change of endometrial carcinogenesis, has been reported to occur at a high frequency in the endometrium of normal premenopausal women, although few of these cases progress to cancer. It was hypothesized that the 50% to 60% reduced cancer risk attributed to oral contraceptives (OCPs) and intrauterine devices (IUDs) occurred in part through their activity as negative selection factors for these subclinical mutated glands.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>A total of 71 women with a history of OCP use and 80 with a history of IUD use were age matched with 191 and 119 controls, respectively. Endometrial biopsy specimens were immunostained for PTEN, and each was scored for the presence or absence of PTEN\u2010null glands (latent precancer).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>The frequency of latent precancers was found to be significantly reduced in OCP\u2012exposed (13%; odds ratio [OR], 0.19 [<jats:italic>P<\/jats:italic> &lt; .001]) and IUD\u2012exposed (18%; OR, 0.42 [<jats:italic>P<\/jats:italic> = .015]) women compared with respective matched controls (43% and 34%). The presence or absence of endometritis did not appear to be significantly correlated with PTEN status within the IUD\u2010exposed group (<jats:italic>P<\/jats:italic> = .24).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>Normal\u2010appearing <jats:italic>PTEN<\/jats:italic> mutated endometrial glands, which are highly prevalent in the normal population, may be targets of endometrial cancer risk\u2012modulating exposures. Some exposures reported to diminish the incidence of endometrial cancer in epidemiologic outcome studies, including OCP and IUD use, are associated with a proportionate decline in the frequency of latent precancers. Involution of pre\u2010existing endometrial latent precancers, as evaluated by PTEN analysis, may provide an accessible surrogate marker for long\u2010term endometrial cancer risk. Cancer 2009. \u00a9 2009 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.24218","type":"journal-article","created":{"date-parts":[[2009,3,11]],"date-time":"2009-03-11T10:55:32Z","timestamp":1236768932000},"page":"2111-2118","source":"Crossref","is-referenced-by-count":19,"title":["Involution of latent endometrial precancers by hormonal and nonhormonal mechanisms"],"prefix":"10.1002","volume":"115","author":[{"given":"Ming\u2010Chieh","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyla A.","family":"Burkholder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akila N.","family":"Viswanathan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna","family":"Neuberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George L.","family":"Mutter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,4,28]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64656-1"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.11.924"},{"key":"e_1_2_7_4_2","first-page":"4311","article-title":"Molecular identification of latent precancers in histologically normal endometrium","volume":"61","author":"Mutter GL","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_2_7_5_2","volume-title":"SEER Cancer Statistics Review, 1975\u20102002","author":"Ries LAG","year":"2005"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2003.11.026"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4321"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2007.01.002"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(95)90125-6"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008945721786"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020337528607"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-7824(99)00014-1"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-1154"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197901043000103"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2004.021071"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65040-7"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65227-3"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800347"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1119\/1.1636492"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2007.09.023"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21058"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.24218","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.24218","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T18:07:44Z","timestamp":1760292464000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.24218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4,28]]},"references-count":20,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2009,5,15]]}},"alternative-id":["10.1002\/cncr.24218"],"URL":"https:\/\/doi.org\/10.1002\/cncr.24218","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,4,28]]}}}