Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network

Nat Commun. 2019 Nov 26;10(1):5385. doi: 10.1038/s41467-019-13266-3.


The disproportionately high prevalence of male cancer is poorly understood. We tested for sex-disparity in the functional integrity of the major tumor suppressor p53 in sporadic cancers. Our bioinformatics analyses expose three novel levels of p53 impact on sex-disparity in 12 non-reproductive cancer types. First, TP53 mutation is more frequent in these cancers among US males than females, with poorest survival correlating with its mutation. Second, numerous X-linked genes are associated with p53, including vital genomic regulators. Males are at unique risk from alterations of their single copies of these genes. High expression of X-linked negative regulators of p53 in wild-type TP53 cancers corresponds with reduced survival. Third, females exhibit an exceptional incidence of non-expressed mutations among p53-associated X-linked genes. Our data indicate that poor survival in males is contributed by high frequencies of TP53 mutations and an inability to shield against deregulated X-linked genes that engage in p53 networks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, X*
  • Exome
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, X-Linked
  • Humans
  • Male
  • Mutation Rate*
  • Neoplasms / genetics*
  • Neoplasms / mortality
  • Protein Interaction Maps
  • SEER Program
  • Sex Factors
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • United States / epidemiology


  • TP53 protein, human
  • Tumor Suppressor Protein p53