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MLH1 −93G>A promoter polymorphism and risk of mismatch repair deficient colorectal cancer
Author(s) -
Allan James M.,
Shorto Jennifer,
Adlard Julian,
Bury Jonathan,
Coggins Ron,
George Rina,
Katory Mark,
Quirke Philip,
Richman Susan,
Scott Daniel,
Scott Kathryn,
Seymour Matthew,
Travis Lois B.,
Worrillow Lisa J.,
Bishop D. Timothy,
Cox Angela
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23770
Subject(s) - mlh1 , colorectal cancer , oncology , dna mismatch repair , medicine , biology , cancer research , cancer , genetics
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.