{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T13:24:05Z","timestamp":1740144245694,"version":"3.37.3"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T00:00:00Z","timestamp":1720828800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T00:00:00Z","timestamp":1720828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP16cm0106503","JP17cm0106503","JP18cm0106503","JP19cm0106503","JP20cm0106503","JP21cm0106503"],"award-info":[{"award-number":["JP16cm0106503","JP17cm0106503","JP18cm0106503","JP19cm0106503","JP20cm0106503","JP21cm0106503"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Tailored, preventive cancer care requires the identification of pathogenic germline variants (PGVs) among potentially at-risk blood relatives (BRs). Cascade testing is carried out for BRs of probands who are positive for PGVs of an inherited cancer but not for negative probands. This study was conducted to examine the prevalence of PGVs for BRs of PGV-negative probands.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>PGV prevalence was assessed for 682 BRs of 281 probands with <jats:italic>BRCA1\/BRCA2<\/jats:italic> wild-type hereditary breast and ovarian cancer (HBOC) syndrome.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>PGVs were discovered in 22 (45.8%) of the 48 BRs of the PGV-positive probands and in 14 (2.2%) of 634 BRs of the PGV-negative probands. Eleven PGVs on high-risk <jats:italic>BRCA1<\/jats:italic>, <jats:italic>BRCA2<\/jats:italic>, and <jats:italic>TP53<\/jats:italic> genes were present only in BRs and not in the probands (probands vs BRs in Fisher exact test; <jats:italic>p<\/jats:italic>\u2009=\u20090.0104; odds ratio [OR]\u2009=\u20090.000 [0.000\u20130.5489 of 95% confidence interval]), partly due to the nature of the selection criteria. The enrichment of high-risk PGVs among BRs was also significant as compared with a non-cancer East Asian population (<jats:italic>p<\/jats:italic>\u2009=\u20090.0016; OR\u2009=\u20093.0791 [1.5521\u20135.6694]). PGV prevalence, risk class of gene, and genotype concordance were unaffected by the cancer history among BRs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>These findings imply the necessity to construct a novel testing scheme to complement cascade testing.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12282-024-01615-0","type":"journal-article","created":{"date-parts":[[2024,7,13]],"date-time":"2024-07-13T17:01:49Z","timestamp":1720890109000},"page":"1028-1036","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High-risk pathogenic germline variants in blood relatives of BRCA1\/2 negative probands"],"prefix":"10.1007","volume":"31","author":[{"given":"Reiko","family":"Yoshida","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Kaneyasu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arisa","family":"Ueki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideko","family":"Yamauchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shozo","family":"Ohsumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Ohno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichi","family":"Baba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Kawano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomichi","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masao","family":"Nagasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Ueno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Inari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusuke","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Takei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Gotoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuyo","family":"Nishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miki","family":"Okamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keika","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megumi","family":"Okawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Misato","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayuri","family":"Amino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayuko","family":"Inuzuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuo","family":"Noda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8569-4504","authenticated-orcid":false,"given":"Seiichi","family":"Mori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seigo","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,7,13]]},"reference":[{"key":"1615_CR1","unstructured":"National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology for genetic\/familial high-risk assessment: breast, ovarian, and pancreatic (version 3.2023)."},{"key":"1615_CR2","doi-asserted-by":"crossref","unstructured":"Committee on Gynecologic P. ACOG Committee Opinion No. 727: cascade testing: testing women for known hereditary genetic mutations associated with cancer. Obstet Gynecol. 2018;131:e31\u2013e4.","DOI":"10.1097\/AOG.0000000000002457"},{"key":"1615_CR3","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1200\/PO.21.00163","volume":"5","author":"KD Whitaker","year":"2021","unstructured":"Whitaker KD, Obeid E, Daly MB, Hall MJ. Cascade genetic testing for hereditary cancer risk: an underutilized tool for cancer prevention. JCO Precis Oncol. 2021;5:1387\u201396.","journal-title":"JCO Precis Oncol"},{"key":"1615_CR4","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1093\/jnci\/djy147","volume":"111","author":"JL Caswell-Jin","year":"2019","unstructured":"Caswell-Jin JL, Zimmer AD, Stedden W, Kingham KE, Zhou AY, Kurian AW. Cascade genetic testing of relatives for hereditary cancer risk: results of an online initiative. J Natl Cancer Inst. 2019;111:95\u20138.","journal-title":"J Natl Cancer Inst"},{"key":"1615_CR5","doi-asserted-by":"publisher","first-page":"4241","DOI":"10.1002\/cncr.34482","volume":"128","author":"MK Frey","year":"2022","unstructured":"Frey MK, Ahsan MD, Badiner N, Lin J, Narayan P, Nitecki R, et al. What happens in the long term: uptake of cancer surveillance and prevention strategies among at-risk relatives with pathogenic variants detected via cascade testing. 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Other authors have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Approval of the research protocol by an Institutional Reviewer Board: This study was approved by the internal review board (IRB) at each of 6 institutions. The main IRB was Showa University IRB.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statement"}},{"value":"Written informed consent was obtained from all participants (probands, BRs, and spouses).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}