Polymorphism at the glutathione S-transferase M1 and T1 gene loci: a studyof the frequencies of the genotypes in a Slovak population

The incidence of cancer varies markedly by ethnicity and geographic locatio n. Epidemiological studies suggest that ethnic differences in cancer occurr ence can result from differences in inherited susceptibility. Since the maj ority of chemical carcinogens are not capable of causing hazardous effects per se, the metabolism of these compounds is a crucial part of the initial host response to the environmental exposure. Disturbances in the balance be tween activation and detoxification may, therefore, explain the individual variations in responses to exposures to carcinogens. Many of the metabolic enzymes have recently been shown to express genetic polymorphisms in the po pulation and an association has been found between environmentally induced cancer and the polymorphism of these genes. The mu (GSTM1) and theta (GSTT1 ) members of the glutathione S-transferase multigene family are candidates as cancer susceptibility genes because of their ability to regulate the con jugation of carcinogenic compounds to excretable hydrophilic metabolites. I ndividuals who are carriers of homozygous deletions in the GSTM1 or GSTT1 g enes may have an impaired ability to metabolically eliminate carcinogenic c ompounds and, therefore, may be at increased cancer risk. In our study, rye identified GSTM1 and GSTT1 genotypes in a community-based sample of 248 he althy, unrelated individuals from Slovakia. Our study was based on molecula r genetic testing (polymerase chain reaction (PCR) - based method). in cont rast to most earlier studies which were based on phenotypical measurements of enzyme activity. Mie used the simultaneous amplification of GSTM1 and GS TT1 genomic fragments in the same reaction. On the basis of the results fro m our pooled control samples, we estimate that, in the geographic region of our study (Slovakia), 49.6 % of individuals are carriers of the GSTM1 0/0 genotype and 16.9% of individuals are homozygous GSTT1 deletion carriers. T he fact that deletion polymorphisms in GSTM1 or GSTT1 are common implies th at the population attributable risk associated with these genotypes may be quite high. These findings will be of importance in the determination of ca ncer risk in the population.