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Kravis Center for Molecular Oncology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017556","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MSK Precision and Interception Program"},{"name":"MSK Robert and Kate Niehaus Center for Inherited Genomics"}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Age at diagnosis among patients with cancer is a predictor of pathogenic germline variant prevalence, yet age thresholds often misclassify genetic risk. We performed germline sequencing of 39,184 unselected patients with solid malignancies spanning 32 tumor types, interrogating &amp;gt;90 cancer predisposition genes independent of clinical suspicion. Patients were stratified into early-, average-, and late-onset groups based on standard deviations from tumor-specific mean age at diagnosis. Pathogenic variant prevalence inversely correlated with age at diagnosis: 18.4% in early-onset tumors, 15.6% in average-onset tumors, and 12.3% in late-onset tumors (P &amp;lt; 0.001). Variants in high\/moderate-penetrance genes accounted for the enrichment in early-onset cases (12.4%, early-onset; 8.9%, average-onset; 5.1%, late-onset; P &amp;lt; 0.001). Restricting hereditary cancer testing to patients diagnosed before age 50, as is typically done, would miss 4,601 pathogenic variant carriers, 72% of all variants detected. These findings support broad-based germline testing beyond conventional age-based criteria, reflecting the burden of hereditary risk even among late-onset cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>Across 32 solid tumor types in a pan-cancer cohort, we found enrichment of germline pathogenic variants among patients with subtype-specific early-onset cancer. Using age 50 as a testing cutoff misses most patients with inherited predisposition, supporting universal germline genetic testing for all individuals diagnosed with cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-26-0971","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:03:03Z","timestamp":1791432183000},"page":"OF1-OF9","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Universal Germline Genetic Testing after a Diagnosis of Cancer"],"prefix":"10.1158","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6985-2864","authenticated-orcid":false,"given":"Zsofia K.","family":"Stadler","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02yrq0923","id-type":"ROR","asserted-by":"publisher"}],"name":"Memorial Sloan Kettering Cancer Center 1 Precision and Interception Program, , New York, New York."},{"id":[{"id":"https:\/\/ror.org\/02yrq0923","id-type":"ROR","asserted-by":"publisher"}],"name":"Memorial Sloan Kettering Cancer Center 2 Division of Solid Tumor Oncology, , New York, New York."},{"id":[{"id":"https:\/\/ror.org\/02yrq0923","id-type":"ROR","asserted-by":"publisher"}],"name":"Memorial Sloan Kettering Cancer Center 3 Robert and Kate Niehaus Center for Inherited Cancer Genomics, , New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4605-9684","authenticated-orcid":false,"given":"Anna","family":"Maio","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02yrq0923","id-type":"ROR","asserted-by":"publisher"}],"name":"Memorial Sloan Kettering Cancer Center 1 Precision and Interception Program, , New York, New York."},{"id":[{"id":"https:\/\/ror.org\/02yrq0923","id-type":"ROR","asserted-by":"publisher"}],"name":"Memorial Sloan Kettering Cancer Center 4 Department of Nursing, , New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3726-6382","authenticated-orcid":false,"given":"Aliya","family":"Khurram","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02yrq0923","id-type":"ROR","asserted-by":"publisher"}],"name":"Memorial Sloan Kettering Cancer Center 1 Precision and Interception Program, , New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9537-8708","authenticated-orcid":false,"given":"Kanika","family":"Arora","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02yrq0923","id-type":"ROR","asserted-by":"publisher"}],"name":"Memorial Sloan Kettering Cancer Center 5 Department of Pathology and Laboratory Medicine, , New York, New York."},{"id":[{"id":"https:\/\/ror.org\/02yrq0923","id-type":"ROR","asserted-by":"publisher"}],"name":"Memorial Sloan Kettering Cancer Center 6 Marie-Jos\u00e9e and Henry R. 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