Mismatch repair gene MSH3 polymorphism is associated with the risk of sporadic prostate cancer

J Urol. 2008 May;179(5):2020-4. doi: 10.1016/j.juro.2008.01.009. Epub 2008 Mar 20.


Purpose: The mismatch repair system is a DNA repair mechanism that corrects mispaired bases during DNA replication errors. Cancer cells deficient in MMR proteins have a 10(2) to 10(3)-fold increase in the mutation rate. Single nucleotide polymorphisms of mismatch repair genes have been shown to cause a decrease in DNA repair activity. We hypothesized that mismatch repair gene polymorphism could be a risk factor for prostate cancer and p53 Pro/Pro genotype carriers could influence MSH3 and MSH6 polymorphisms.

Materials and methods: DNA samples from 110 patients with prostate cancer and 110 healthy controls were analyzed by single strand conformational polymorphism and polymerase chain reaction-restriction fragment length polymorphism to determine the genotypic frequency of 5 polymorphic loci on 2 MMR genes (MSH3 and MSH6) and p53 codon72. The chi-square test was applied to compare genotype frequency between patients and controls.

Results: A significant increase in the G/A+A/A genotype of MSH3 Pro222Pro was observed in patients compared to controls (OR 1.87, 95% CI 1.0-3.5). The frequency of A/G + G/G genotypes of MSH3 exon23 Thr1036Ala also tended to increase in patients (OR 1.57, 95% CI 0.92-2.72). In p53 codon72 Arg/Pro + Pro/Pro carriers the frequency of the AG + GG genotype of MSH3 exon23 was significantly increased in patients compared to controls (OR 2.1, 95% CI 1.05-4.34).

Conclusions: To our knowledge this is the first report of the association of MSH3 gene polymorphisms in prostate cancer. These results suggest that the MSH3 polymorphism may be a risk factor for prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Base Pair Mismatch*
  • DNA Mismatch Repair*
  • DNA-Binding Proteins / genetics*
  • Genes, p53 / genetics
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • MutS Homolog 3 Protein
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single-Stranded Conformational
  • Prostatic Neoplasms / genetics*


  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • Genetic Markers
  • MSH3 protein, human
  • MutS Homolog 3 Protein