{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:16:39Z","timestamp":1761718599810,"version":"3.37.3"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T00:00:00Z","timestamp":1501804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572506"],"award-info":[{"award-number":["81572506"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Von Hippel\u2010Lindau (<jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content>) disease is a rare autosomal dominant cancer syndrome caused by alterations of <jats:italic><jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content><\/jats:italic> gene. Patients are predisposed to develop pheochromocytomas and solid or cystic tumors of the central nervous system, kidney, pancreas, and retina. Remarkable phenotypic heterogeneity exits in organ involvement and tumor onset age between and within <jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content> families. However, no reliable markers have been found to predict the age\u2010related tumor risks in <jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content> patients. A large Chinese cohort composed of 300 <jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content> patients and 92 healthy family controls was enrolled in our study. Blood relative telomere length was measured in 184 patients and all the controls available for genomic <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> samples. Age\u2010related risks for the five major <jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content>\u2010associated tumors were evaluated using Kaplan\u2013Meier plots and Cox regression analysis. Differences in clinical phenotype were observed between Chinese cohort and the United Kingdom cohort. <jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content> patients showed significantly shorter telomere length than healthy family controls(<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0183), and a positive correlation was found between telomere length and onset age of the five major tumors, respectively. Moreover, patients in the shorter telomere group (age\u2010adjusted telomere length\u00a0\u2264\u00a00.44) suffered higher age\u2010related risks for <jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content>\u2010associated central nervous system hemangioblastomas (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>: 1.879, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.004), renal cell carcinoma (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>: 2.126, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002) and pancreatic cyst and neuroendocrine tumors (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>: 2.093, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.001). These results indicate that blood shorter telomere length is a new biomarker for age\u2010related tumor risks in <jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content> patients, which will be crucial to genetic counseling and future research about the role of telomere shortening in the pathogenesis of <jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content>\u2010associated tumors.<\/jats:p>","DOI":"10.1002\/cam4.1134","type":"journal-article","created":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T11:27:18Z","timestamp":1501846038000},"page":"2131-2141","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Shorter telomere length increases age\u2010related tumor risks in von Hippel\u2010Lindau disease patients"],"prefix":"10.1002","volume":"6","author":[{"given":"Jiang\u2010Yi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology Peking University First Hospital  Beijing China"},{"name":"Institute of Urology Peking University  Beijing China"},{"name":"National Urological Cancer Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang\u2010He","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Urology Peking University First Hospital  Beijing China"},{"name":"Institute of Urology Peking University  Beijing China"},{"name":"National Urological Cancer Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang\u2010Hui","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Urology Peking University First Hospital  Beijing China"},{"name":"Institute of Urology Peking University  Beijing China"},{"name":"National Urological Cancer Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology Peking University First Hospital  Beijing China"},{"name":"Institute of Urology Peking University  Beijing China"},{"name":"National Urological Cancer Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng\u2010Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology Peking University First Hospital  Beijing China"},{"name":"Institute of Urology Peking University  Beijing China"},{"name":"National Urological Cancer Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia\u2010Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology Peking University First Hospital  Beijing China"},{"name":"Institute of Urology Peking University  Beijing China"},{"name":"National Urological Cancer Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao\u2010An","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Urology Peking University First Hospital  Beijing China"},{"name":"Institute of Urology Peking University  Beijing China"},{"name":"National Urological Cancer Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nie\u2010Nie","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Urology Peking University First Hospital  Beijing China"},{"name":"Institute of Urology Peking University  Beijing China"},{"name":"National Urological Cancer Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Urology Peking University First Hospital  Beijing China"},{"name":"Institute of Urology Peking University  Beijing China"},{"name":"National Urological Cancer Center  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo\u2010Wen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Urology 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