Occurrence and Specific Type of p53 and H-ras Mutations Based on Polymorphisms of NAT2 and GSTM1 in Human Bladder Cancer

Kim, Wun Jae; Lee, Sang Cheol; Woo, Seung Hyo; Kim, Heon

Abstract

PURPOSE: Cancer development depends on not only activation of oncogene or inactivation of tumor suppressor gene but also activities of enzymes involved in the metabolism of various carcinogenic xenobiotics, such as arylamine N-acetyltrasferase 2(NAT 2) and glutathione S-transferase (GSTM1). We analyzed whether genetic polymorphisms of NAT2 and GSTM1 were correlated with the mutation patterns of p53 and H-ras genes in bladder tumor tissues.
MATERIALS AND METHODS
In 49 bladder cancer patients, we performed direct DNA sequencing for the detection of mutations of p53 and H-ras gene in bladder tumor tissues, and adopted PCR and PCR-RFLP techniques for the analysis of genetic polymorphisms of NAT2 and GSTM1 using patients` blood samples, respectively.
RESULTS
In 18 cases, mutations in p53 were detected whereas 1 case carried two mutations; thus total of 19 mutations were detected. Sixteen of these were point mutations including 13 of transversions and 3 of transitions, and others were 1 of frameshift and 2 of microdeletions-insertions. Among 33 patients, H-ras mutations were detected in 5 cases with 2 of transitions and 3 of transversions. The frequencies of slow, intermediate, and rapid acetylator in NAT2 genotyping analysis, were 10.2%, 40.8%, and 49.0%, respectively, and GSTM1 deletions were observed in 73.5%. We could not find any significant correlations between NAT2 or GSTM1 polymorphisms and the occurence of p53(p=0.614, p=0.310) or H-ras(p=0.500, p=0.582) mutations. Also, no apparent associations were seen for specific type of p53 and H-ras mutations according to polymorphisms of NAT2(p=0.456, p=0.600) and GSTM1(p=0.378, p=0.400).
CONCLUSIONS
The polymorphisms of NAT2 and GSTM1, conjugating enzymes of foreign compound metabolism, were not considered to influence occurrence and type of mutations in p53 and H-ras in human bladder cancer.