{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T11:36:38Z","timestamp":1758281798016,"version":"3.44.0"},"reference-count":65,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>Survivors of childhood cancers are at risk of second malignant neoplasms (SMNs). Exposure to radiation therapy and different chemotherapy agents are known risk factors for SMN development. However, there remains interindividual variability that could be attributed to genetic variations. Our study aims to identify rare genetic variants associated with SMN risk and assess the influence of treatment on the associated risk of these variants.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>MATERIALS AND METHODS<\/jats:title>\n            <jats:p>We conducted a whole-exome sequencing in a nested case-control study within the French Childhood Cancer Survivors Study for 450 survivors including 163 cases and 287 controls. Rare variants in genes within replication, recombination, and repair pathways were selected. Gene-based association tests were conducted and a logistic regression analysis was used to estimate the effect of selected genes on SMN risk, adjusting for relevant clinical variables. Specific analysis restricted to breast and thyroid SMNs were also performed. Stratified analyses on the basis of the radiation doses received by the bone marrow and specific organs were also conducted.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              We have identified several genetic associations: the\n              <jats:italic toggle=\"yes\">RNASEL<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">APOBEC3F<\/jats:italic>\n              genes (odds ratio [OR], 5.43 [95% CI, 1.76 to 20.44];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .0055 and OR, 4.8 [95% CI, 1.28 to 22.95];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .027, respectively) are associated with the risk of SMN, while the\n              <jats:italic toggle=\"yes\">FANCM<\/jats:italic>\n              gene (OR, 4.65 [95% CI, 1.06 to 21.56];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .041) is associated with the risk of developing breast SMN.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>This study provides new evidence regarding the involvement of genetics in the development of SMN. Additional research is needed to confirm these results and uncover the underlying mechanisms behind these associations. If replicated, these findings will help identify survivors at higher risk of developing SMN, enabling tailored treatment and follow-up strategies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po-24-00668","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T19:59:13Z","timestamp":1758139153000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Rare Variants Associated With Pediatric Cancer Treatment\u2013Related Second Malignant Neoplasm Risk"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9485-8056","authenticated-orcid":true,"given":"Claire","family":"Ducos","sequence":"first","affiliation":[{"name":"Radiation Epidemiology Team, Center for Research in Epidemiology and Population Health, INSERM Unit 1018, Villejuif, France"},{"name":"Research Department, Gustave Roussy, Villejuif, France"},{"name":"University Paris Saclay, Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7603-7828","authenticated-orcid":true,"given":"Brice","family":"Fresneau","sequence":"additional","affiliation":[{"name":"Radiation Epidemiology Team, Center for Research in Epidemiology and Population Health, INSERM Unit 1018, Villejuif, France"},{"name":"Research Department, Gustave Roussy, Villejuif, France"},{"name":"University Paris Saclay, Villejuif, France"},{"name":"Department of Children and Adolescents Oncology, Gustave Roussy Cancer Campus, Universit\u00e9 Paris-Saclay, Villejuif, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippo","family":"Rosselli","sequence":"additional","affiliation":[{"name":"CNRS UMR9019, Gustave Roussy Cancer Campus, Universit\u00e9 Paris-Saclay, Equipe Labellis\u00e9e Ligue Nationale Contre le Cancer, Villejuif, 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