The MLH1 promoter contains a common single nucleotide polymorphism (−93 guanine > adenine) located in an essential region for maximum transcriptional activity. This has been associated with an increased risk of microsatellite instability (MSI) colorectal cancer. The aim of the study was to compare the distribution of MLH1 −93G>A genotypes between patients with familial colon cancer, sporadic colon cancer and healthy subjects.
We genotyped 200 familial colon samples, 183 cases of sporadic colon cancer and 236 control subjects. MSI was analysed.
The GA genotype was under-represented in patients with familial colon cancer, whereas the AA genotype was over-represented in cases of sporadic colon cancer. A greater frequency of the MLH1 GA genotype was found in the cancer cases with MLH1 focal immunohistochemistry (IHC) for anti-MLH1 antibody. When we compared genotype distribution in the familial colorectal cancer cases with and without MSI, we failed to detect any correlation, although the GA genotype is more frequent in cases with MSI.
There is a relationship between the MLH1 −93G>A polymorphism in the homozygous state and the risk of sporadic colorectal cancer. The variant MLH1 −93G>A appears to be related to cases with focal IHC activity more than to complete absence of the MLH1 protein in the tumour tissue.