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MUTYH: Not just polyposis.

Maria Cristina Curia1, Teresa Catalano2, Gitana Maria Aceto3

  • 1Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Via dei Vestini 66100, Italy. mc.curia@unich.it.

World Journal of Clinical Oncology
|August 22, 2020
PubMed
Summary

MUTYH is a DNA repair enzyme crucial for correcting oxidative damage. Its mutations are linked to colorectal polyposis, but this review explores its broader role in various cancers and diseases, suggesting new therapeutic targets.

Keywords:
Base excision repairColorectal cancerMUTYHMutationsPolyposisSingle nucleotide polymorphism

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Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • MUTYH is a base excision repair enzyme vital for DNA integrity, correcting errors from guanine oxidation.
  • It functions as an adenine DNA glycosylase, cooperating with OGG1 to mitigate oxidative stress.
  • Mutations in MUTYH are associated with MUTYH-associated polyposis (MAP), increasing gastrointestinal cancer risk.

Purpose of the Study:

  • To review the multifaceted role of MUTYH beyond colorectal cancer.
  • To investigate the association of MUTYH single nucleotide polymorphisms (SNPs) with various neoplastic and non-neoplastic diseases.
  • To explore MUTYH as a potential therapeutic target for diverse pathologies.

Main Methods:

  • Literature review of current studies on MUTYH in human diseases.
  • Analysis of the association between MUTYH mutations/SNPs and cancer/non-cancer diseases.
  • Evaluation of recent advances in understanding MUTYH's molecular pathogenesis.

Main Results:

  • MUTYH pathogenic variants are linked to increased risk of extraintestinal cancers (duodenum, ovary, bladder) and endocrine tumors.
  • MUTYH variants predict poor prognosis in sporadic gastric cancer and salivary gland secretory carcinoma.
  • MUTYH SNPs are associated with lung, hepatocellular, and cervical cancer risks, and potentially neurological/ocular diseases.

Conclusions:

  • MUTYH plays a significant role in preventing various diseases, including those linked to oxidative stress.
  • Understanding MUTYH's diverse functions offers insights into novel therapeutic strategies.
  • Further research on MUTYH is essential for identifying new therapeutic targets and improving cancer treatment.