{
  "abstract": "Epidemiological data demonstrate a marked male bias in incidence and mortality across most non-reproductive cancers. Beyond behavioral and hormonal factors, recent genomic insights highlight the critical role of X-chromosome genetics and epigenetics. Specifically, genes that escape X-chromosome inactivation (XCI)-termed Escape from X-Inactivation Tumor Suppressors (EXITS)-provide a female-specific \"dosage protection\" mechanism against oncogenesis. This review analyzes seven X-linked tumor suppressor genes associated with sex-biased cancer phenotypes (KDM6A, KDM5C, DDX3X, ATRX, PHF6, MAGEC3, and CNKSR2) and their roles in cancer etiology and tumor suppression. Under the two-hit hypothesis, female cells-with two X chromosomes-can offset a loss-of-function mutation on the active X chromosome through normal allele expression from the inactive X chromosome (Xi), lowering susceptibility. Conversely, males with only one X chromosome face a \"single-hit vulnerability,\" in which a single loss-of-function mutation disrupts the tumor-suppressor network. We further note persistent knowledge gaps regarding the remaining X-linked tumor suppressors annotated in the TSGene 2.0 database, reflecting the facultative nature of XCI escape, limited statistical power in existing cohorts, and the underuse of single-cell multi-omic approaches. Elucidating XCI escape and X-linked gene dosage imbalances offers a framework for sex-specific precision oncology. For high-risk male populations, identifying EXITS gene mutations warrants more intensive, shorter-interval screening. In female patients, epigenetic modulators that induce X-reactivation of Xi may offer unique therapeutic benefits. Incorporating X-linked gene dosage parameters into clinical trials and drug development will be essential to overcome sex disparities in cancer prevention and therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, College of Science and Technology, Duksung Women's University Seoul Korea."
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sori Han",
      "orcid": "0009-0000-6816-8641"
    },
    {
      "affs": [
        0
      ],
      "name": "Sun Young Kim",
      "orcid": "0000-0002-5994-8889"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5wtqjjgymfymf.bib",
  "cited_by": 0,
  "doi": "10.15430/jcp.26.041",
  "fulltext_url": "https://europepmc.org/articles/PMC13739628",
  "id": "5wtqjjgymfymf",
  "issns": [
    "2288-3649",
    "2288-3657"
  ],
  "landing_url": "https://europepmc.org/article/MED/42996556",
  "language": "eng",
  "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": [
    [
      "openalex",
      "1311|Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities"
    ]
  ],
  "openalex": "W7213953921",
  "pdf_url": "https://europepmc.org/articles/PMC13739628?pdf=render",
  "pmcid": "PMC13739628",
  "pmid": "42996556",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5wtqjjgymfymf.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:41Z",
      "native_id": "MED:42996556",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42996556"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "X-linked Tumor Suppressor Escape and Sex Dimorphism in Cancer: Implications for Risk Stratification and Prevention.",
  "title_text": "X-linked Tumor Suppressor Escape and Sex Dimorphism in Cancer: Implications for Risk Stratification and Prevention.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:41Z",
  "url": "https://research.draconitic.com/paper/5wtqjjgymfymf",
  "venue": "Journal of cancer prevention",
  "versions": []
}