Biologia, Bratislava 54/Suppl. 6: 157-162, 1999.

ISSN 0006-3088 (Biologia). ISSN 1335-6399 (Biologia. Section Cellular and Molecular Biology).

 

Full paper

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

 

Jan Salagovic1*, Ivan Kalina1, Viera Habalova1, Jan Stubna2, Anton Kohut3 & Erik Biros1

1 Department of Medical Biology, School of Medicine, P. J. Safarik University, Tr. SNP 1, SK-04066 Kosice, Slovakia; tel.: ++421 95 640 4376, fax: ++421 95 642 8151, e-mail: salagov@central.medic.upjs.sk

2 Department of Tuberculosis and Respiratory Diseases, University Hospital, Rastislavova 43, SK-04190 Kosice, Slovakia

3 Department of Pharmacology, School of Medicine, P. J. Safarik University, Tr. SNP 1, SK-04066 Kosice, Slovakia

* corresponding author

Received: September 14, 1998 / Accepted: October 5, 1999

 

Abstract

The incidence of cancer varies markedly by ethnicity and geographic location. Epidemiological studies suggest that ethnic differences in cancer occurrence can result from differences in inherited susceptibility. Since the majority 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 between 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 population and an association has been found between environmentally induced cancer and the polymorphism of these genes. The m (GSTM1) and q (GSTT1) members of the glutathione S-transferase multigene family are candidates as cancer susceptibility genes because of their ability to regulate the conjugation of carcinogenic compounds to excretable hydrophilic metabolites. Individuals who are carriers of homozygous deletions in the GSTM1 or GSTT1 genes may have an impaired ability to metabolically eliminate carcinogenic compounds and, therefore, may be at increased cancer risk. In our study, we identified GSTM1 and GSTT1 genotypes in a community-based sample of 248 healthy, unrelated individuals from Slovakia. Our study was based on molecular genetic testing (polymerase chain reaction (PCR) - based method), in contrast to most earlier studies which were based on phenotypical measurements of enzyme activity. We used the simultaneous amplification of GSTM1 and GSTT1 genomic fragments in the same reaction. On the basis of the results from 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. The fact that deletion polymorphisms in GSTM1 or GSTT1 are common implies that the population attributable risk associated with these genotypes may be quite high. These findings will be of importance in the determination of cancer risk in the population.

 

Key words: cancer risk, individual susceptibility, genetic polymorphism, glutathione S-transferase M1 and T1, ethnicity.