{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:31:19Z","timestamp":1789428679808,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Wide\u2010spread use of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators has resulted in a dramatic increase in life expectancy of people with CF. Historically,\n                      <jats:italic>CFTR<\/jats:italic>\n                      carrier status has been thought to be benign; however, data are emerging that dysfunction of\n                      <jats:italic>CFTR<\/jats:italic>\n                      may play a role in cancer risk. The aims of this study were to (1) determine the frequency of germline pathogenic\n                      <jats:italic>CFTR<\/jats:italic>\n                      gene variations in a cohort of patients with cancer, and (2) investigate associations between germline pathogenic\n                      <jats:italic>CFTR<\/jats:italic>\n                      variants and established germline somatic oncogenic driver mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The Indiana University Adult Precision Genomics (APG) clinical database was queried for all subjects having a germline\n                      <jats:italic>CFTR<\/jats:italic>\n                      pathogenic variant (PV). The\n                      <jats:italic>CFTR<\/jats:italic>\n                      PVs observed in our cohort were compared to published population minor allele frequencies from the Allele Frequency Aggregator (ALFA) Project then scaled to reflect our APG population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Data were available for 2141 patients. Based on known minor allele frequencies and the racial distribution of our cohort, we expected 33 subjects (1.5%) to have\n                      <jats:italic>CFTR<\/jats:italic>\n                      PVs. However,\n                      <jats:italic>CFTR<\/jats:italic>\n                      PVs were present in 71 subjects (3.3%), 2.1\u2010fold higher than expected (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The observed enrichment of\n                      <jats:italic>CFTR<\/jats:italic>\n                      PVs varied by cancer type, with\n                      <jats:italic>CFTR<\/jats:italic>\n                      PVs being overrepresented in patients with skin and gastrointestinal cancers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The overall prevalence of\n                      <jats:italic>CFTR<\/jats:italic>\n                      PVs in people with solid tumors was higher than expected. These results suggest that carriers of\n                      <jats:italic>CFTR<\/jats:italic>\n                      PV may benefit from enhanced cancer screening.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ppul.71360","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T13:53:18Z","timestamp":1761659598000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Enrichment of Germline Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Pathogenic Variants in Patients With Solid Tumors: Evidence for Increased Cancer Risk"],"prefix":"10.1002","volume":"60","author":[{"given":"Tyler","family":"Shugg","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Gallaway","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Powell","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd C.","family":"Skaar","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Bray","sequence":"additional","affiliation":[{"name":"Fountain Life Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh Anne","family":"Stout","sequence":"additional","affiliation":[{"name":"Division of Medical and Molecular Genetics, Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Indiana University Health Precision Genomics Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3804-9267","authenticated-orcid":false,"given":"Abi","family":"Colwell","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia D.","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Sleep, and Occupational Medicine Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Slaven","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8019-9811","authenticated-orcid":false,"given":"Emma M.","family":"Tillman","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Cystic Fibrosis Foundation Cystic Fibrosis Foundation Patient Registry 2023 Annual Data Report. 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