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TBD patients are at increased risk of certain types of squamous cell carcinomas and hematological malignancies. However, most studies on cancer incidence in TBDs involved relatively young cohorts in which patients with pulmonary fibrosis were underrepresented or absent. Therefore, we investigated cancer incidence in patients with pulmonary fibrosis as major manifestation of TBD (TBD-PF) with a pathogenic (P), likely pathogenic (LP), and variant of unknown significance (VUS) TRG-variant and compared it to the general population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      TBD-PF patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009177) were retrospectively included and cancer history was collected. For each cancer type the observed number of cancers was compared with the expected number adjusted for age and sex based on data of the Netherlands Cancer Registry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The TBD-PF cohort (median age 62.8 years, 63% male), consisted of 114 P\/LP and 63 VUS carriers. Restricting the analyses to P\/LP variant carriers we observed 14 patients with cancer (solid cancer\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098 (7.0%); hematological cancer\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096 (5.3%)). The observed all-cancer incidence (12.3%) was comparable to expected (18.9%) in the general population, Observed\/Expected incidence 0.6 (95%CI 0.4-1.0). Regarding cancer types, only myelodysplastic syndrome was significantly more frequently observed than expected (Observed\/Expected\u2009=\u200956 (95%CI 21\u2013117)). There were no significant differences in clinical characteristics and transplant-free survival between TBD-PF patients with and without cancer. Comparable results were obtained when patients with TRG variants classified as VUS were included.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>All-cancer risk for TBD-PF patients was comparable to the general population. However, TBD-PF patients have an increased risk of developing myelodysplastic syndrome, underlining the importance of tailored genetic counselling and hematological surveillance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12931-025-03469-2","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T13:35:05Z","timestamp":1768829705000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cancer risk in patients with pulmonary fibrosis and a rare telomere related gene variant"],"prefix":"10.1186","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6727-8416","authenticated-orcid":false,"given":"Joanne J.","family":"van der Vis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn T. 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The Medical Research Ethics Committees United of the St. Antonius Hospital approved the ILD Biobank study (R05-08\u00a0A), and written informed consent was obtained from all participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Charlotte I. de Bie, Jasper, J. van der Smagt, Laura G. M. Daenen, Matthijs F.M. van Oosterhout and Jan C. Grutters has nothing to disclose; J.J. van der Vis received, via her institution a lecture fee from Chiesi Pharmaceuticals BV., Coline H.M. van Moorsel received, via her institution, grants from the pulmonary fibrosis foundation, Boehringer Ingelheim BV and TZO grant ZonMW and a lecture fee from Boehringer Ingelheim. Martijn T.K. Maus received a personal lecture fee from Chiesi Pharmaceuticals BV.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"61"}}