MLH1 -93G>A promoter polymorphism and risk of mismatch repair deficient colorectal cancer (2008)

Author(s): Allan JM , Shorto J, Adlard J, Bury J, Coggins R, George R, Katory M, Quirke P, Richman S, Scott D, Scott K, Seymour M, Travis LB, Worrillow LJ, Bishop DT, Cox A

    Abstract: Rare inherited mutations in the mutL homolog 1 (MLH1) DNA mismatch repair gene can confer an increased susceptibility to colorectal cancer (CRC) with high penetrance where disease frequently develops in the proximal colon. The core promoter of MLH1 contains a common single nucleotide polymorphism (SNP) (-93G>A, dbSNP ID:rs1800734) located in a region essential for maximum transcriptional activity. We used logistic regression analysis to examine the association between this variant and risk of CRC in patients in the United Kingdom. All statistical tests were 2 sided. In an analysis of 1,518 patients with CRC, homozygosity for the MLH1 -93A variant was associated with a significantly increased 3-fold risk of CRC negative for MLH1 protein by immunohistochemistry (odds ratio (OR): AA vs GG = 3.30, 95% CI 1.46-7.47, n = 1392, p = 0.004, MLH1 negative vs MLH1 positive CRC) and with a 68% excess of proximal CRC (OR: AA vs GG=1.68, 95% confidence interval (CI) 1.00-2.83, n = 1,518, p = 0.05, proximal vs distal CRC). These findings suggest that the MLH1 -93G>A polymorphism defines a low penetrance risk allele for CRC. © 2008 Wiley-Liss, Inc.

      • Date: 19-08-2008
      • Journal: International Journal of Cancer
      • Volume: 123
      • Issue: 10
      • Pages: 2456-2459
      • Publisher: John Wiley & Sons, Inc.
      • Publication type: Article
      • Bibliographic status: Published

      Keywords: MLH1 mismatch repair colorectal polymorphism proximal promoter dna repair cancer


      Professor James Allan
      Professor of Cancer Genetics