{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:43:52Z","timestamp":1753868632322,"version":"3.41.2"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T00:00:00Z","timestamp":1660089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["DRO 00064203"],"award-info":[{"award-number":["DRO 00064203"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Nijmegen breakage syndrome (NBS) is an autosomal\u2010recessive chromosome instability disorder characterized by, among others, hypersensitivity to X\u2010irradiation and an exceptionally high risk for lymphoid malignancy. The vast majority of NBS patients is homozygous for a common Slavic founder mutation, c.657del5, of the <jats:italic>NBN<\/jats:italic> gene, which is involved in the repair of DNA double\u2010strand breaks (DSBs). The founder mutation also predisposes heterozygous carriers to cancer, apparently however, with a higher risk in the Czech Republic\/Slovakia (CS) than in Poland.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To examine whether the age of cancer manifestation and cancer death of <jats:italic>NBN<\/jats:italic> homozygotes is different between probands from CS and Poland.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study is restricted to probands born until 1989, before replacement of the communist regime by a democratic system in CS and Poland, and a substantial transition of the health care systems. Moreover, all patients were recruited without knowledge of their genetic status since the <jats:italic>NBN<\/jats:italic> gene was not identified until 1998.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we show that cancer manifestation of <jats:italic>NBN<\/jats:italic> homozygotes is at a significantly earlier age in probands from CS than from Poland. This is explained by the difference in natural and medical radiation exposure, though within the permissible dosage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>It is reasonable to assume that this finding also sheds light on the higher cancer risk of <jats:italic>NBN<\/jats:italic> heterozygotes in CS than in Poland. This has implications for genetic counseling and individualized medicine also of probands with other DNA repair defects.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cnr2.1700","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:24:30Z","timestamp":1660177470000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The <i>NBN<\/i> founder mutation\u2014Evidence for a country specific difference in age at cancer manifestation"],"prefix":"10.1002","volume":"6","author":[{"given":"Krystyna H.","family":"Chrzanowska","sequence":"first","affiliation":[{"name":"Department of Medical Genetics The Children's Memorial Health Institute  Warsaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Seemanova","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Institute of Biology and Medical Genetics, 2nd Medical School Charles University  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymonda","family":"Varon","sequence":"additional","affiliation":[{"name":"Institute of Medical and Human Genetics Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Digweed","sequence":"additional","affiliation":[{"name":"Institute of Medical and Human Genetics Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorota","family":"Piekutowska\u2010Abramczuk","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics The Children's Memorial Health Institute  Warsaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2305-4370","authenticated-orcid":false,"given":"Karl","family":"Sperling","sequence":"additional","affiliation":[{"name":"Institute of Medical and Human Genetics Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel","family":"Seeman","sequence":"additional","affiliation":[{"name":"DNA Laboratory, Department of Pediatric Neurology, 2nd Medical School Charles University, University Hospital Motol  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-13"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81174-5"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2004.03.004"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.07.029"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jrr\/rrw031"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-062917-012415"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/get048"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djm251"},{"key":"e_1_2_9_10_1","first-page":"IX","article-title":"Cancer risk and fertility of NBS heterozygotes in Poland. 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