POLYMORPHISM OF DNA MISMATCH REPAIR GENES IN ENDOMETRIAL CANCER

Endometrial cancer (EC) is the second most common malignancy associated with hereditary non-polyposis colorectal cancer (HNPCC) family. The development of HNPCC is associated with defects in DNA mismatch repair (MMR) pathway resulting in microsatellite instability (MSI). MSI is present in a greater number of EC than can be accounted for by inherited MMR mutations, therefore alternative mechanisms may underline defective MMR in EC, including polymorphic variation. Aim: We checked the association between EC occurrence and two polymorphisms of MMR genes: a 1032G>A (rs4987188) transition in the hMSH2 gene resulting in a Gly22Asp substitution and a –93G>A (rs1800734) transition in the promoter of the hMLH1 gene. Material and methods: These polymorphisms were genotyped in DNA from peripheral blood lymphocytes of 100 EC patients and 100 age-matched women by restriction fragment length polymorphism PCR. Results: A positive association (OR 4.18; 95% CI 2.23–7.84) was found for the G/A genotype of the –93G>A polymorphism of the hMLH1 gene and EC occurrence. On the other hand, the A allele of this polymorphism was associated with decreased EC occurrence. The Gly/Gly genotype slightly increased the effect of the –93G>A-G/A genotype (OR 4.52; CI 2.41–8.49). Our results suggest that the –93G>A polymorphism of the hMLH1 gene singly and in combination with the Gly322Asp polymorphism of the hMSH2 gene may increase the risk of EC.

The relationship between human muth homolog 1 gene mutation at site 415 and sporadic colon cancers in Chinese Han population

Background: The genetic factors of colon cancer play an important role in the tumor development and growth. The incidence of colon cancers has greatly increased in China. However, few data is available for the relationship between human muth homolog 1 (hMLH1) gene mutation at site 415 and sporadic colon cancers in Chinese population. Objective: Investigate the relationship between G→C mutation in hMLH1 gene at site 415 and sporadic colon cancers in Chinese Han population. Methods: Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing techniques, the genotype of the hMLH1 gene was analyzed at site 415 in 97 cases of sporadic colon cancer patients and 138 controls. Reverse-transcription (RT)-PCR was used to determine the level of hMLH1 mRNA expression in normal colonic mucosa of patients with different genotype. Results: The frequency of genotype C/C at the 415 site of the hMLH1 gene was significantly higher in colon cancer patients than in controls. The expression levels of hMLH1 mRNA in normal colonic mucosa were similar in colon cancer patients with different genotypes. Conclusion: G’!C mutation in hMLH1 gene at site 415 may represent a genetic factor that is associated with sporadic colon cancer in a small group of Chinese Han population.