{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:57:12Z","timestamp":1792000632978,"version":"4.4.0"},"reference-count":33,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Females exposed prenatally to diethylstilbestrol (DES) have an elevated risk of cervical dysplasia, breast cancer, and clear cell adenocarcinoma (CCA) of the cervix\/vagina. Testicular cancer risk is increased in prenatally exposed males. Epigenetic changes may mediate the transmission of DES effects to the next (\u201cthird\u201d) generation of offspring. Methods: Using data self-reported by third-generation females, we assessed DES in relation to the risk of cancer and benign breast and reproductive tract conditions. Using data from prenatally DES-exposed and unexposed mothers, we assessed DES in relation to cancer risk in their female and male offspring. Cancer risk was assessed by standardized incidence ratios (SIR) and 95% confidence intervals (CI); the risks of benign and malignant diagnoses were assessed by hazard ratios (HR) and 95% CI. Results: In self-reported data, DES exposure was not associated with an increased risk of overall cancer (HR 0.83; CI 0.36\u20131.90), breast cancer, or severe cervical dysplasia. No females reported CCA. The risk of borderline ovarian cancer appeared elevated, but the HR was imprecise (3.46; CI 0.37\u201332.42). Based on mothers\u2019 reports, DES exposure did not increase the risk of overall cancer (HR 0.80; CI 0.49\u20131.32) or of other cancers in third-generation females. Overall cancer risk in exposed males appeared elevated (HR 1.41; CI 0.70\u20132.86), but the CI was wide. The risk of testicular cancer was not elevated in exposed males; no cases of prostate cancer were reported. Conclusions: To date, there is little evidence that DES is associated with cancer risk in third-generation females or males, but these individuals are relatively young, and further follow-up is needed.<\/jats:p>","DOI":"10.3390\/cancers16142575","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T10:39:26Z","timestamp":1721299166000},"page":"2575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Benign and Malignant Outcomes in the Offspring of Females Exposed In Utero to Diethylstilbestrol (DES): An Update from the NCI Third Generation Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Linda","family":"Titus","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Geisel School of Medicine at Dartmouth, and the Norris Cotton Cancer Center, Lebanon, NH 03756, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth E.","family":"Hatch","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly A.","family":"Bertrand","sequence":"additional","affiliation":[{"name":"Boston University Chobanian & Avedisian School of Medicine and Slone Epidemiology Center, Boston University, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie R.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Boston University Chobanian & Avedisian School of Medicine and Slone Epidemiology Center, Boston University, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Strohsnitter","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dezheng","family":"Huo","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9155-5006","authenticated-orcid":false,"given":"Michael","family":"Curry","sequence":"additional","affiliation":[{"name":"Information Management Services, Rockville, MD 20852, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0548-2312","authenticated-orcid":false,"given":"Marianne","family":"Hyer","sequence":"additional","affiliation":[{"name":"Information Management Services, Rockville, MD 20852, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjersti","family":"Aagaard","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine and Texas Children\u2019s Hospital, Houston, TX 77401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0165-5522","authenticated-orcid":false,"given":"Gretchen L.","family":"Gierach","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Troisi","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/S0002-9378(16)38617-3","article-title":"Does the administration of diethylstilbestrol during pregnancy have therapeutic value?","volume":"66","author":"Dieckmann","year":"1953","journal-title":"Am. 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