Role of DNA repair systems in malignant tumor development in the elderly

The increased incidence of malignant neoplasms in the elderly is related to the accumulation of damaged DNA. We focused on the molecular mechanisms of the DNA repair system and examined its relationship to malignant neoplasms in the elderly. Hypermethylation of the promoter region of a mismatch repair gene is strongly associated with gastric and colorectal carcinomas occurring in the elderly. These tumors have characteristic features such as the absence of hMLH1 expression, microsatellite instability, poorly differentiated histology, low incidence of lymph node metastasis and favorable prognosis. On the other hand, we analyzed single nucleotide polymorphism (SNP) of the genes in the DNA repair system such as hOGG1, p53, XRCC1 and hMLH1 in autopsy cases. Although no significant associations were found between the SNP and the number of malignant neoplasms, a few SNP were associated with specific tumors. These findings suggest that epigenetic changes in the DNA mismatch repair genes play important roles in the development of gastric and colorectal carcinomas and that the SNP of DNA repair genes have little influence on the occurrence of carcinoma in the elderly.