{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T17:43:38Z","timestamp":1788716618796,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["K08CA234394"],"award-info":[{"award-number":["K08CA234394"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA33572"],"award-info":[{"award-number":["P30CA33572"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA242218"],"award-info":[{"award-number":["R01CA242218"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["RC4CA153828"],"award-info":[{"award-number":["RC4CA153828"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001006","name":"Breast Cancer Research Foundation","doi-asserted-by":"publisher","award":["BCRF\u201019\u2010172"],"award-info":[{"award-number":["BCRF\u201019\u2010172"]}],"id":[{"id":"10.13039\/100001006","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To identify additional at\u2010risk groups for lung cancer screening, which targets persons with a long history of smoking and thereby misses younger or nonsmoking cases, the authors evaluated germline pathogenic variants (PVs) in patients with lung adenocarcinoma for an association with an accelerated onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The authors assembled a retrospective cohort (1999\u20102018) of oncogenetic clinic patients with lung adenocarcinoma. Eligibility required a family history of cancer, data on smoking, and a germline biospecimen to screen via a multigene panel. Germline PVs (\n                      <jats:italic>TP53\/EGFR<\/jats:italic>\n                      ,\n                      <jats:italic>BRCA2<\/jats:italic>\n                      , other Fanconi anemia [FA] pathway genes, and non\u2010FA DNA repair genes) were interrogated for associations with the age at diagnosis via an accelerated failure time model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Subjects (n = 187; age, 28\u201089 years; female, 72.7%; Hispanic, 11.8%) included smokers (minimum of 5 pack\u2010years; n = 65) and nonsmokers (lighter ever smokers [n = 18] and never smokers [n = 104]). Overall, 26.7% of the subjects carried 1 to 2 germline PVs:\n                      <jats:italic>TP53<\/jats:italic>\n                      (n = 5),\n                      <jats:italic>EGFR<\/jats:italic>\n                      (n = 2),\n                      <jats:italic>BRCA2<\/jats:italic>\n                      (n = 6), another FA gene (n = 11), or another DNA repair gene (n = 28). After adjustment for smoking, sex, and ethnicity, the diagnosis of lung adenocarcinoma was accelerated 12.2 years (95% confidence interval [CI], 2.5\u201020.6 years) by\n                      <jats:italic>BRCA2<\/jats:italic>\n                      PVs, 9.0 years (95% CI, 0.5\u201016.5 years) by\n                      <jats:italic>TP53\/EGFR<\/jats:italic>\n                      PVs, and 6.1 years (95% CI, \u20131.0 to 12.6 years) by PVs in other FA genes. PVs in other DNA repair genes showed no association. Germline associations did not vary by smoking.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Among lung adenocarcinoma cases, germline PVs (\n                      <jats:italic>TP53<\/jats:italic>\n                      ,\n                      <jats:italic>EGFR<\/jats:italic>\n                      ,\n                      <jats:italic>BRCA2<\/jats:italic>\n                      , and possibly other FA genes) may be associated with an earlier onset. With further study, the criteria for lung cancer screening may need to include carriers of high\u2010risk PVs, and findings could influence precision therapy and reduce lung cancer mortality by earlier stage diagnosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.33573","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T15:25:16Z","timestamp":1618586716000},"page":"2801-2806","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Germline mutations and age at onset of lung adenocarcinoma"],"prefix":"10.1002","volume":"127","author":[{"given":"Karen L.","family":"Reckamp","sequence":"first","affiliation":[{"name":"City of Hope Comprehensive Cancer Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn E.","family":"Behrendt","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P.","family":"Slavin","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy W.","family":"Gray","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle K.","family":"Castillo","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Koczywas","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela C.","family":"Cristea","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten M.","family":"Babski","sequence":"additional","affiliation":[{"name":"Sutter Roseville Medical Center Roseville California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Stearns","sequence":"additional","affiliation":[{"name":"Waukesha\u2010Pro Health Waukesha Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Marcum","sequence":"additional","affiliation":[{"name":"Catholic Health Initiatives Chattanooga Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yenni P.","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Clinica del Country, Centro de Oncologia Bogota Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amie J.","family":"Hass","sequence":"additional","affiliation":[{"name":"Mercy Medical Center Cedar Rapids Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Vecchio","sequence":"additional","affiliation":[{"name":"Hunterdon Cancer Center Flemington New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Mora","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Enfermedades Neoplasicas Lima Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleck E.","family":"Cervantes","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon R.","family":"Sand","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa M.","family":"Mejia","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8821-3921","authenticated-orcid":false,"given":"Terrence C.","family":"Tsou","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Salgia","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6714-092X","authenticated-orcid":false,"given":"Jeffrey N.","family":"Weitzel","sequence":"additional","affiliation":[{"name":"City of Hope Comprehensive Cancer Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21442"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21228"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djw295"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602769"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-017-3287-4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2017.08.011"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2016-0030"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1671"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000052"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0000000000000130"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1978757"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-003-0968-7"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.6959"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3002"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2018.06.016"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1196-253"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.15.1310"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.028829"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20128"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2017.08.001"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-017-0019-5"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_24_1","unstructured":"KanehisaM.Fanconi anemia pathway. KEGG PATHWAY Database. Accessed October 28 2020.https:\/\/www.genome.jp\/kegg\u2010bin\/show_pathway?ko03460"},{"key":"e_1_2_8_25_1","unstructured":"Molecular Signatures Database v7.3 Gene Set: GOBP_DNA_REPAIR.Gene Set Enrichment Analysis. Published 2020. Accessed April 1 2021.http:\/\/www.gsea\u2010msigdb.org\/gsea\/msigdb\/cards\/GOBP_DNA_REPAIR.html"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.00328"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.42.1586"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.33573","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncr.33573","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.33573","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:49:45Z","timestamp":1760266185000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.33573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,15]]},"references-count":26,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1002\/cncr.33573"],"URL":"https:\/\/doi.org\/10.1002\/cncr.33573","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,15]]},"assertion":[{"value":"2020-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}