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The\n                    <jats:italic>TP53<\/jats:italic>\n                    variant p.R181H is enriched in the Swedish germline\n                    <jats:italic>TP53<\/jats:italic>\n                    cohort and has distinct phenotypical characteristics. Using our nationwide Swedish germline\n                    <jats:italic>TP53<\/jats:italic>\n                    database (SWEP53, 189 individuals, 86 families), p.R181H was identified in 22% of families (19\/86), compared to just 0.6% in the National Cancer Institute (NCI)\n                    <jats:italic>TP53<\/jats:italic>\n                    database (8\/1360). Notably, p.R181H carriers had lower cancer incidence and better survival than carriers of other\n                    <jats:italic>TP53<\/jats:italic>\n                    variants (both p\u2009&lt;\u20090.0001). Female carriers primarily developed breast cancer (earliest onset 29\u00a0years), males mainly prostate cancer (earliest onset 45\u00a0years), and no cancers were observed in children. The results were confirmed using the NCI\n                    <jats:italic>TP53<\/jats:italic>\n                    database. Tumor sequencing confirmed loss of heterozygosity. Additionally, haplotype analysis suggests that p.R181H is a potential Swedish founder variant, estimated to be ~\u2009550\u00a0years old. These findings indicate that, for p.R181H carriers, tailored surveillance could focus on adults by omitting children from testing and surveillance, and by targeting prevention and detection to breast cancer in females and prostate cancer in males. Validation in independent cohorts is warranted.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-22407-2","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T19:41:23Z","timestamp":1759866083000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["TP53 p.R181H is enriched in the Swedish cohort (SWEP53) and associated with a distinct breast and prostate phenotype"],"prefix":"10.1038","volume":"15","author":[{"given":"Alexander","family":"Sun Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meis","family":"Omran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Arthur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Malmgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Barbosa-Matos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Seixas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Tham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Bajalica-Lagercrantz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"22407_CR1","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1038\/s41431-020-0638-4","volume":"28","author":"T Frebourg","year":"2020","unstructured":"Frebourg, T. et al. 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