MSH2 and cancer: While the cancer risk associated with pathogenic MLH1 variants is significant, studies have shown that the MMR mechanism is not as sensitive to expression decrease in the MLH1 gene as it is to those in MSH2 and MSH6 genes (31) This could imply that the cancer risk associated to MLH1 is more sensitive to other cellular activities, such as DNA damage signaling shown to be more sensitive to decreases in MLH1 expression than the MMR mechanism (59).