{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:42:41Z","timestamp":1792453361652,"version":"4.5.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R21 CA261833"],"award-info":[{"award-number":["R21 CA261833"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"C. Im and Y. Yuan, principal investigators","award":["R01 CA283333"],"award-info":[{"award-number":["R01 CA283333"]}]},{"name":"C. Im and Z. Wang, principal investigators","award":["R01 CA216354"],"award-info":[{"award-number":["R01 CA216354"]}]},{"name":"Y. Yasui and J. Zhang, principal investigators","award":["U24 CA55727"],"award-info":[{"award-number":["U24 CA55727"]}]},{"name":"G.T. Armstrong, principal investigator","award":["U01 CA195547"],"award-info":[{"award-number":["U01 CA195547"]}]},{"name":"M.M. Hudson and K.K. Ness, principal investigators"},{"name":"Cancer Center Support","award":["CA21765"],"award-info":[{"award-number":["CA21765"]}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL173881"],"award-info":[{"award-number":["R01 HL173881"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Children\u2019s Cancer Research Fund"},{"name":"University of Minnesota Foundation Pediatric Scholar"},{"DOI":"10.13039\/100012524","name":"American Lebanese Syrian Associated Charities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012524","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Female survivors of childhood cancer are at high risk for developing breast cancer. The contributions of most general population primary breast cancer genetic predictors to this risk have not been explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Analyses included females who survived at least 5\u2009years after their childhood cancer diagnosis with available array (n\u2009=\u20092096; subsequent breast cancer: n = 218) or whole-genome sequencing (n\u2009=\u20093292; subsequent breast cancer: n\u2009=\u2009101) data from the Childhood Cancer Survivor Study and St. Jude Lifetime Cohort. We computed 99 externally validated primary breast cancer polygenic risk scores. Using deep-coverage whole-genome sequencing, ClinVar-annotated pathogenic or likely pathogenic variants in breast cancer susceptibility genes were identified. Cox proportional hazards models assessed associations with subsequent breast cancer risk, adjusting for treatments and genetic ancestry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 5388 female survivors (genetic ancestry, European: n\u2009=\u20094752; African: n\u2009=\u2009444; East Asian: n\u2009=\u2009192), 319 developed subsequent breast cancer. Most (90.9%) polygenic risk scores were nominally associated with subsequent breast cancer risk (P\u2009&amp;lt;\u2009.05), but effect sizes varied substantially. Polygenic risk scores with superior discriminatory ability had greater genome-wide coverage (eg, 6.4 million-variant polygenic risk score, hazard ratio [HR] per SD = 1.71, 95% CI = 1.43 to 2.05; P\u2009=\u20094.2 x 10\u22129) and 7.7-fold higher odds (P\u2009=\u20097.0 x 10\u22124) of including variants in multiple DNA damage repair pathways compared with polygenic risk scores with weaker risk associations. Among survivors with whole-genome sequencing, 1.6% carried pathogenic or likely pathogenic variants in clinical testing panel genes, which was associated with a 7.4-fold greater risk (95% CI = 3.16 to 17.19). Including genetic factors improved subsequent breast cancer risk prediction by age 40 years (P\u2009&amp;lt;\u2009.001) compared with treatment exposures alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Externally validated primary breast cancer genetic susceptibility predictors are relevant for subsequent breast cancer risk prediction and should be prioritized for risk stratification in survivors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djag306","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:50:46Z","timestamp":1788954646000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrating genetic predictors into subsequent breast cancer risk prediction in survivors of childhood 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J","family":"Mills","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota , Minneapolis, MN,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5943-9454","authenticated-orcid":false,"given":"Yadav","family":"Sapkota","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Cancer Control, St. Jude Children\u2019s Research Hospital , Memphis, TN,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoming","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Medicine and College of Artificial Intelligence, Cybersecurity and Computing, University of South Florida , Tampa, FL,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0162-7740","authenticated-orcid":false,"given":"Tianzhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Biostatistics and Health Data Science, School of Public Health, University of Minnesota , Minneapolis, MN,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P","family":"Neglia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota , Minneapolis, MN,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie M","family":"Turcotte","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota , Minneapolis, MN,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6984-2407","authenticated-orcid":false,"given":"Melissa M","family":"Hudson","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Cancer Control, St. Jude Children\u2019s Research Hospital , Memphis, TN,","place":["USA"]},{"name":"Department of Oncology, St. Jude Children\u2019s Research Hospital , Memphis, TN,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten K","family":"Ness","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Cancer Control, St. Jude Children\u2019s Research Hospital , Memphis, TN,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8722-4207","authenticated-orcid":false,"given":"Gregory T","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Cancer Control, St. Jude Children\u2019s Research Hospital , Memphis, TN,","place":["USA"]},{"name":"Department of Oncology, St. Jude Children\u2019s Research Hospital , Memphis, 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