The MLH1 polymorphism rs1800734 and risk of endometrial cancer with microsatellite instability

Clin Epigenetics. 2020 Jul 8;12(1):102. doi: 10.1186/s13148-020-00889-3.


Both colorectal (CRC, 15%) and endometrial cancers (EC, 30%) exhibit microsatellite instability (MSI) due to MLH1 hypermethylation and silencing. The MLH1 promoter polymorphism, rs1800734 is associated with MSI CRC risk, increased methylation and reduced MLH1 expression. In EC samples, we investigated rs1800734 risk using MSI and MSS cases and controls. We found no evidence that rs1800734 or other MLH1 SNPs were associated with the risk of MSI EC. We found the rs1800734 risk allele had no effect on MLH1 methylation or expression in ECs. We propose that MLH1 hypermethylation occurs by different mechanisms in CRC and EC.

Keywords: Endometrial cancer; MLH1; Microsatellite instability; Mismatch repair pathway; Single nucleotide polymorphism; rs1800734.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • DNA Methylation
  • Endometrial Neoplasms / diagnosis
  • Endometrial Neoplasms / genetics*
  • Epigenomics / methods*
  • Female
  • Gene Silencing
  • Humans
  • Meta-Analysis as Topic
  • Microsatellite Instability
  • MutL Protein Homolog 1 / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / genetics
  • Risk Assessment


  • MLH1 protein, human
  • RNA, Messenger
  • MutL Protein Homolog 1