{
  "abstract": "Purpose Germline shelterin variants were linked to sarcoma in a case-enriched cohort. Whether shelterin loss of function predisposes to mesenchymal neoplasia in the general population is unknown. Methods We analyzed rare-variant collapsing associations for five shelterin genes across neoplasm phenotypes in UK Biobank exomes, with Genebass as a second pipeline. Prespecified shelterin and centrosome gene sets were tested by permutation-calibrated statistics against a TP53/RB1/NF1 positive control. Carrier risks were compared with telomere-lengthening predictions. Results Lipoma risk was increased in TERF1 (odds ratio [OR], 3.32; P = 8.4 x10-), POT1, and TERF2IP carriers, and uterine leiomyoma risk in all four core shelterin genes, most strongly POT1 (OR, 2.23; P = 4.0 x 10-); POT1 and TINF2 reproduced in Genebass. TERF1 was also associated with thyroid cancer and monoclonal gammopathy. Neither gene set nor the positive control was associated with self-reported sarcoma. Telomere lengthening accounted for POT1-associated chronic lymphocytic leukemia risk but not myeloma or TINF2-associated thyroid cancer, where observed risk exceeded prediction five- to seven-fold. Conclusion Shelterin loss of function is a population-level risk factor for lipoma and uterine leiomyoma, the benign counterparts of liposarcoma and leiomyosarcoma. TERF1 joins POT1 and TINF2 as long-telomere cancer genes. Sarcoma-specific penetrance remains untested.",
  "abstract_shown": true,
  "affiliations": [
    "Stanford University School of Medicine"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "B. D. Lin"
    },
    {
      "name": "K. H.-L. Chan"
    },
    {
      "name": "Z. Zhang"
    },
    {
      "name": "L. Zhi"
    },
    {
      "name": "A. Y. Leow"
    },
    {
      "name": "J. C. Chi"
    },
    {
      "name": "M. Y. Zhou"
    },
    {
      "name": "N. Bui"
    },
    {
      "name": "K. Ganjoo"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Pan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/725z80xbh1e97.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.03.26367209",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.11.03.26367209v1.full",
  "id": "725z80xbh1e97",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.11.03.26367209v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "oncology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.11.03.26367209v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/725z80xbh1e97.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T00:21:02Z",
      "native_id": "10.64898/2026.11.03.26367209",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.11.03.26367209v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:oncology",
      "subfield": "oncology"
    }
  ],
  "title": "Germline Shelterin Loss of Function Predisposes to Lipoma and Uterine Leiomyoma: Population Evidence Bearing on Shelterin-Associated Sarcoma Risk",
  "title_text": "Germline Shelterin Loss of Function Predisposes to Lipoma and Uterine Leiomyoma: Population Evidence Bearing on Shelterin-Associated Sarcoma Risk",
  "type": "preprint",
  "updated_at": "2026-11-07T00:20:51Z",
  "url": "https://research.draconitic.com/paper/725z80xbh1e97",
  "venue": "medRxiv",
  "versions": []
}