{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T09:42:12Z","timestamp":1777542132292,"version":"3.51.4"},"reference-count":23,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,4,20]],"date-time":"2015-04-20T00:00:00Z","timestamp":1429488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Public Health Service","award":["P01 CA108964"],"award-info":[{"award-number":["P01 CA108964"]}]},{"name":"Public Health Service","award":["P50 CA58236"],"award-info":[{"award-number":["P50 CA58236"]}]},{"name":"Public Health Service","award":["U10 CA37429"],"award-info":[{"award-number":["U10 CA37429"]}]},{"name":"Public Health Service","award":["UM1 CA182883"],"award-info":[{"award-number":["UM1 CA182883"]}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000892","name":"Prostate Cancer Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000892","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Telomeres are repetitive nucleoproteins that help maintain chromosomal stability by inhibiting exonucleolytic degradation, prohibiting inappropriate homologous recombination, and preventing chromosomal fusions by suppressing double\u2010strand break signals. We recently observed that men treated for clinically localized prostate cancer with shorter telomeres in their cancer\u2010associated stromal cells, in combination with greater variation in cancer cell telomere lengths, were significantly more likely to progress to distant metastases, and die from their disease. Here, we hypothesized that shorter stromal cell telomere length would be associated with prostate cancer risk at time of biopsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Telomere\u2010specific fluorescence in situ hybridization (FISH) analysis was performed in normal\u2010appearing stromal, basal epithelial, and luminal epithelial cells in biopsies from men randomized to the placebo arm of the Prostate Cancer Prevention Trial. Prostate cancer cases (N\u2009=\u200932) were either detected on a biopsy performed for cause or at the end of the study per trial protocol, and controls (N\u2009=\u200950), defined as negative for cancer on an end\u2010of\u2010study biopsy performed per trial protocol (e.g., irrespective of indication), were sampled. Logistic regression was used to estimate the association between mean telomere length of the particular cell populations, cell\u2010to\u2010cell telomere length variability, and risk of prostate cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Men with short stromal cell telomere lengths (below median) had 2.66 (95% CI 1.04\u20133.06; <jats:italic>P\u2009<\/jats:italic>=\u20090.04) times the odds of prostate cancer compared with men who had longer lengths (at or above median). Conversely, we did not observe statistically significant associations for short telomere lengths in normal\u2010appearing basal (OR\u2009=\u20092.15, 95% CI 0.86\u20135.39; <jats:italic>P<\/jats:italic>=\u20090\u2009.10) or luminal (OR\u2009=\u20091.15, 95% CI 0.47\u20132.80; <jats:italic>P\u2009<\/jats:italic>=\u20090.77) cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that telomere shortening in normal stromal cells is associated with prostate cancer risk. It is essential to extend and validate these findings, while also identifying the cellular milieu that comprises the subset of cells with short telomeres within the prostate tumor microenvironment. <jats:italic>Prostate 75: 1160\u20131166, 2015<\/jats:italic>. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.22997","type":"journal-article","created":{"date-parts":[[2015,4,20]],"date-time":"2015-04-20T11:53:24Z","timestamp":1429530804000},"page":"1160-1166","source":"Crossref","is-referenced-by-count":29,"title":["Prostate stromal cell telomere shortening is associated with risk of prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial"],"prefix":"10.1002","volume":"75","author":[{"given":"Christopher M.","family":"Heaphy","sequence":"first","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine Baltimore Maryland"},{"name":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaurav","family":"Gaonkar","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah B.","family":"Peskoe","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinne E.","family":"Joshu","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland"},{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo M.","family":"De Marzo","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine Baltimore Maryland"},{"name":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland"},{"name":"Department of Urology and the James Buchanan Brady Urological Institute Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Scott","family":"Lucia","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phyllis J.","family":"Goodman","sequence":"additional","affiliation":[{"name":"SWOG Statistical Center, and the Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott M.","family":"Lippman","sequence":"additional","affiliation":[{"name":"Moores Cancer Center University of California San Diego California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Ian M.","family":"Thompson","sequence":"additional","affiliation":[{"name":"UT Health Science Center at San Antonio San Antonio Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth A.","family":"Platz","sequence":"additional","affiliation":[{"name":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland"},{"name":"Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore Maryland"},{"name":"Department of Urology and the James Buchanan Brady Urological Institute Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan K.","family":"Meeker","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine Baltimore Maryland"},{"name":"Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland"},{"name":"Department of Urology and the James Buchanan Brady Urological Institute Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,4,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2011.01284.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/350569a0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.41.110306.130350"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2848"},{"key":"e_1_2_7_6_1","first-page":"6405","article-title":"Telomere shortening is an early somatic DNA alteration in human prostate tumorigenesis","volume":"62","author":"Meeker AK","year":"2002","journal-title":"Cancer 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