Specific variants in the MLH1 gene region may drive DNA methylation, loss of protein expression, and MSI-H colorectal cancer.

Publication Type:

Journal Article


PloS one, Volume 5, Issue 10, p.e13314 (2010)


2010, Adaptor Proteins, Signal Transducing, Aged, Center-Authored Paper, Colorectal Neoplasms, DNA Methylation, Epidemiology Core Facility, Female, GENOMIC INSTABILITY, Humans, Logistic Models, Male, Microsatellite Repeats, Middle Aged, Nuclear Proteins, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Public Health Sciences Division, Shared Resources, Specimen Processing Core Facility


We previously identified an association between a mismatch repair gene, MLH1, promoter SNP (rs1800734) and microsatellite unstable (MSI-H) colorectal cancers (CRCs) in two samples. The current study expanded on this finding as we explored the genetic basis of DNA methylation in this region of chromosome 3. We hypothesized that specific polymorphisms in the MLH1 gene region predispose it to DNA methylation, resulting in the loss of MLH1 gene expression, mismatch-repair function, and consequently to genome-wide microsatellite instability.