Mar. 22, 2007 Patients with a variant of a DNA repair gene, known as MLH1, may have an increased risk of a subtype of colorectal cancer, according to a study in the March 21 issue of the Journal of the National Cancer Institute.
Mismatch repair genes fix problems that arise during DNA replication when bases are incorrectly paired. Mutations in these repair genes are associated with increased risks of cancer.
Stavroula Raptis and Miralem Mrkonjic, graduate students at the University of Toronto, and colleagues analyzed two DNA mismatch repair genes, MLH1 and MSH2, in 1,359 colorectal cancer patients and 1,373 controls from Ontario and Newfoundland.
One particular variant in the MLH1 gene, -93G>A, was strongly associated with colorectal cancer. Patients with two copies of this version of the gene had a greater risk of colorectal cancer than patients with only one.
"Decreased levels of MLH1 expression associated with [MLH1 -93G>A] may lead to impaired cell cycle control, allowing cells to proceed with cell division before proper DNA repair can be accomplished. This impaired control would overwhelm the mismatch repair mechanism, leading to the accumulation of mutations," the authors write.
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