A promoter polymorphism in the hMLH1 gene (-93G/A) associated with sporadic colorectal cancer.

Colorectal cancer (CRC) is a worldwide problem for public health. mutL homolog 1 (MLH1) is a key component of the mismatch repair system, and the MLH1-93G/A polymorphism (rs1800734) is predicted to affect MLH1 protein expression, suggesting that the polymorphism may be associated with the cancer risk; however, the results concerning this have been inconsistent. In order to investigate the possible correlation between human (h)MLH1-93G/A polymorphism and the development and progression of sporadic CRC (SCRC) in China, the genotypes of hMLH1-93G/A were detected by the TaqMan MGB probe method in 312 SCRC patients and 300 healthy controls, and immunohistochemical staining was also performed to measure the expression of hMLH1 in cases with different alleles among the SCRC patients and normal controls. It was observed that the A/A genotype and A allele significantly increased the risk of developing Duke's stage C+D CRC and lymphatic metastasis. hMLH1 expression of the A allele was lower than that of the G allele in CRC. By contrast, there was no statistically significant difference in hMLH1 expression for the A allele and the G allele in the normal controls. These results suggested that hMLH1-93G/A polymorphism may not be associated with the overall risk of CRC, but that the hMLH1-93A/A genotype and A allele are associated with the progression of CRC.