{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:50:35Z","timestamp":1785333035594,"version":"3.55.0"},"reference-count":39,"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":[[2025,6]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>The prevalence of pathogenic\/likely pathogenic germline variants (PGVs) in gastric cancer (GC) predisposition genes is not well understood. We aimed to determine this in patients with GC undergoing germline genetic testing at a large commercial laboratory.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>This was a cross-sectional study. Retrospective review of genetic testing in patients with GC at a commercial laboratory (Invitae Corp) from March 2015 to July 2023 was performed. Prevalence of PGVs was determined and compared with a control cohort of 20,139 individuals unaffected by cancer. Data were abstracted from test requisition forms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              In total, 3,706 patients with GC underwent genetic testing, of which 494 (13.3%) patients carried PGVs, 1,200 (32.4%) had variants of uncertain significance, and 1,890 (51%) had negative testing. PGVs were identified in 38 genes, of which 385 of 494 (77.9%) were in a gene previously associated with GC, including 35% in homologous recombination repair genes (\n              <jats:italic toggle=\"yes\">BRCA1<\/jats:italic>\n              ,\n              <jats:italic toggle=\"yes\">BRCA2<\/jats:italic>\n              ,\n              <jats:italic toggle=\"yes\">PALB2<\/jats:italic>\n              , and\n              <jats:italic toggle=\"yes\">ATM<\/jats:italic>\n              ), 19.5% in Hereditary Diffuse GC genes (\n              <jats:italic toggle=\"yes\">CDH1<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">CTNNA1<\/jats:italic>\n              ), and 17.4% in Lynch syndrome genes (\n              <jats:italic toggle=\"yes\">MLH1<\/jats:italic>\n              ,\n              <jats:italic toggle=\"yes\">MSH2<\/jats:italic>\n              ,\n              <jats:italic toggle=\"yes\">MSH6<\/jats:italic>\n              ,\n              <jats:italic toggle=\"yes\">PMS2<\/jats:italic>\n              , and\n              <jats:italic toggle=\"yes\">EPCAM<\/jats:italic>\n              ). Comparing the GC cohort with the unaffected cohort, it was found that there was significant enrichment of PGVs in most GC-associated genes, except for\n              <jats:italic toggle=\"yes\">APC<\/jats:italic>\n              ,\n              <jats:italic toggle=\"yes\">EPCAM<\/jats:italic>\n              ,\n              <jats:italic toggle=\"yes\">MUTYH<\/jats:italic>\n              , and\n              <jats:italic toggle=\"yes\">PMS2<\/jats:italic>\n              . Odds of carrying a PGV was increased significantly in males and patients with a personal history of another cancer with odds ratio (OR) of 1.3 (95% CI, 1.1 to 1.6) and OR, 1.4 (95% CI, 1.1 to 1.7), respectively.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>In this large study of genetic testing in patients with GC, more than one in eight patients referred for germline testing was found to harbor a PGV in a cancer predisposition gene, which is higher than previous estimates. Most PGVs were identified in genes previously associated with GC.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po-24-00620","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T19:59:18Z","timestamp":1749067158000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Prevalence of Pathogenic Germline Variants in Patients With Gastric Cancer Ascertained Through Multigene Panel Testing"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1724-2164","authenticated-orcid":true,"given":"Ophir","family":"Gilad","sequence":"first","affiliation":[{"name":"Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6163-4168","authenticated-orcid":true,"given":"Emma","family":"Keel","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9151-0310","authenticated-orcid":true,"given":"Emily M.","family":"Russell","sequence":"additional","affiliation":[{"name":"Invitae Corporation, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5916-6393","authenticated-orcid":true,"given":"Sarah M.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Invitae Corporation, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4227-3675","authenticated-orcid":true,"given":"Brandie","family":"Heald","sequence":"additional","affiliation":[{"name":"Invitae Corporation, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9205-3756","authenticated-orcid":true,"given":"Edward D.","family":"Esplin","sequence":"additional","affiliation":[{"name":"Invitae Corporation, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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