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MLH1 −93G>A promoter polymorphism and risk of mismatch repair deficient colorectal cancer

✍ Scribed by James M. Allan; Jennifer Shorto; Julian Adlard; Jonathan Bury; Ron Coggins; Rina George; Mark Katory; Philip Quirke; Susan Richman; Daniel Scott; Kathryn Scott; Matthew Seymour; Lois B. Travis; Lisa J. Worrillow; D. Timothy Bishop; Angela Cox; on behalf of the UK NCRI Colorectal Clinical Studies Group; the Colorectal Cancer Study Group

Publisher
John Wiley and Sons
Year
2008
Tongue
French
Weight
83 KB
Volume
123
Category
Article
ISSN
0020-7136

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✦ Synopsis

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.

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