摘要
MUTYH is a base excision repair enzyme,it plays a crucial role in the correction of DNA errors from guanine oxidation and may be considered a cell protective factor.In humans it is an adenine DNA glycosylase that removes adenine misincorporated in 7,8-dihydro-8-oxoguanine(8-oxoG)pairs,inducing G:C to T:A transversions.MUTYH functionally cooperates with OGG1 that eliminates 8-oxodG derived from excessive reactive oxygen species production.MUTYH mutations have been linked to MUTYH associated polyposis syndrome(MAP),an autosomal recessive disorder characterized by multiple colorectal adenomas.MAP patients show a greatly increased lifetime risk for gastrointestinal cancers.The cancer risk in mono-allelic carriers associated with one MUTYH mutant allele is controversial and it remains to be clarified whether the altered functions of this protein may have a pathophysiological involvement in other diseases besides familial gastrointestinal diseases.This review evaluates the role of MUTYH,focusing on current studies of human neoplastic and non-neoplastic diseases different to colon polyposis and colorectal cancer.This will provide novel insights into the understanding of the molecular basis underlying MUTYH-related pathogenesis.Furthermore,we describe the association between MUTYH single nucleotide polymorphisms(SNPs)and different cancer and non-cancer diseases.We address the utility to increase our knowledge regarding MUTYH in the light of recent advances in the literature with the aim of a better understanding of the potential for identifying new therapeutic targets.Considering the multiple functions and interactions of MUTYH protein,its involvement in pathologies based on oxidative stress damage could be hypothesized.Although the development of extraintestinal cancer in MUTYH heterozygotes is not completely defined,the risk for malignancies of the duodenum,ovary,and bladder is also increased as well as the onset of benign and malignant endocrine tumors.The presence of MUTYH pathogenic variants is an independent predic
基金
the Italian Ministry of University and Research,with funds AT-Ricerca2019Curia,FFABRUNIME2019Catalano and AT-Ricerca2019Aceto.
