{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:52:28Z","timestamp":1789426348086,"version":"build-2803163510"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T00:00:00Z","timestamp":1605484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients with PTEN hamartoma tumor syndrome (PHTS, comprising Cowden, Bannayan\u2010Riley\u2010Ruvalcaba, and Proteus\u2010like syndromes) are at increased risk of developing cancer due to pathogenic <jats:italic>PTEN<\/jats:italic> germline variants. This review summarizes age\u2010, sex\u2010, and type\u2010specific malignant cancer risks for PHTS patients, which is urgently needed for clinical management. A PubMed literature search for Standardized Incidence Ratios or Cumulative Lifetime cancer risks (CLTRs) resulted in nine cohort studies comprising four independent PHTS cohorts, including mainly index cases and prevalent cancer cases. The median age at diagnosis was 36\u2009years. Reported CLTRs for any cancer varied from 81% to 90%. The tumor spectrum included female breast cancer (CLTRs including sex\u2010specific estimates at age 60\u201070: 67% to 85%), endometrium cancer (19% to 28%), thyroid cancer (6% to 38%), renal cancer (2% to 24%), colorectal cancer (9% to 32%), and melanoma (0% to 6%). Although these estimates provide guidance for clinical care, discrepancies between studies, sample sizes, retrospective designs, strongly ascertained cases, and lack of pediatric research emphasizes that data should be interpreted with great caution. Therefore, more accurate and more personalized age\u2010, sex\u2010, and cancer\u2010specific risk estimates are needed to enable counseling of all PHTS patients irrespective of ascertainment, and improvement of cancer surveillance guidelines.<\/jats:p>","DOI":"10.1111\/cge.13875","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T05:35:42Z","timestamp":1604381742000},"page":"219-225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["A review on age\u2010related cancer risks in <scp>PTEN<\/scp> hamartoma tumor syndrome"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1008-0265","authenticated-orcid":false,"given":"Linda A.J.","family":"Hendricks","sequence":"first","affiliation":[{"name":"Department of Human Genetics Radboud university medical center  Nijmegen The Netherlands"},{"name":"Radboud university medical center Radboud Institute for Health Sciences  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2393-8141","authenticated-orcid":false,"given":"Nicoline","family":"Hoogerbrugge","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud university medical center  Nijmegen The Netherlands"},{"name":"Radboud university medical center Radboud Institute for Molecular Life Sciences  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke H.M.","family":"Schuurs\u2010Hoeijmakers","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud university medical center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8802-7002","authenticated-orcid":false,"given":"Janet R.","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Radboud university medical center  Nijmegen The Netherlands"},{"name":"Radboud university medical center Radboud Institute for Health Sciences  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11060844"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200289"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2014.10.011"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-013-9674-3"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2283"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-020-0651-7"},{"key":"e_1_2_8_9_1","unstructured":"National Comprehensive Cancer Network. Genetic\/Familial High\u2010Risk Assessment: Breast Ovarian and Pancreatic (Version 1.2020). Cowden Syndrome\/PHTS Management (COWD\u2010A) Website. Accessed July 1 2020"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-018-0071-6"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.0463"},{"key":"e_1_2_8_12_1","unstructured":"Netherlands Cancer Registry. Age\u2010 and type\u2010specific cancer incidence general population in 2012. 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