Tooth agenesis: What do we know and is there a connection to cancer?

Clin Genet. 2021 Apr;99(4):493-502. doi: 10.1111/cge.13892. Epub 2021 Feb 16.


Like all developmental processes, odontogenesis is highly complex and dynamically regulated, with hundreds of genes co-expressed in reciprocal networks. Tooth agenesis (missing one or more/all teeth) is a common human craniofacial anomaly and may be caused by genetic variations and/or environmental factors. Variants in PAX9, MSX1, AXIN2, EDA, EDAR, and WNT10A genes are associated with tooth agenesis. Currently, variants in ATF1, DUSP10, CASC8, IRF6, KDF1, GREM2, LTBP3, and components and regulators of WNT signaling WNT10B, LRP6, DKK, and KREMEN1 are at the forefront of interest. Due to the interconnectedness of the signaling pathways of carcinogenesis and odontogenesis, tooth agenesis could be a suitable marker for early detection of cancer predisposition. Variants in genes associated with tooth agenesis could serve as prognostic or therapeutic targets in cancer. This review aims to summarize existing knowledge of development and clinical genetics of teeth. Concurrently, the review proposes possible approaches for future research in this area, with particular attention to roles in monitoring, early diagnosis and therapy of tumors associated with defective tooth development.

Keywords: WNT pathway; cancer; genetic variants; hypodontia; odontogenesis; oligodontia; predictive marker.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anodontia / epidemiology
  • Anodontia / genetics*
  • Biomarkers, Tumor
  • Carcinogenesis
  • Carcinoma / epidemiology
  • Carcinoma / genetics
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics
  • Early Detection of Cancer
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • MSX1 Transcription Factor / genetics
  • Neoplasms / epidemiology
  • Neoplasms / genetics*
  • Neoplastic Syndromes, Hereditary / epidemiology
  • Neoplastic Syndromes, Hereditary / genetics
  • Odontogenesis
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / genetics
  • PAX9 Transcription Factor / genetics
  • Signal Transduction / genetics
  • Stomach Neoplasms / epidemiology
  • Stomach Neoplasms / genetics
  • Tooth Discoloration
  • Wnt Signaling Pathway / genetics


  • Biomarkers, Tumor
  • MSX1 Transcription Factor
  • MSX1 protein, human
  • PAX9 Transcription Factor
  • PAX9 protein, human