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© 1996 Oxford University Press

research-article

Allelism at the glutathione S-transferase GSTM3 locus: interactions with GSTM1 and GSTT1 as risk factors for astrocytoma

Philip A. Hand, Avis Inskip, Janice Gilford, Julie Alldersea, Jose Elexpuru-Camiruaga 1, John D. Hayes 2, Peter W. Jones 3, Richard C. Strange and Anthony A. Fryer 4

Clinical Biochemistry Research Group, School of Postgraduate Medicine, Keele University Central Pathology Laboratory
1Department of Neurosurgery, North Staffordshire Hospital Stoke-on-Trent
2Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee Dundee, UK
3Department of Mathematics, University of Keele Keele, UK

4To whom correspondence should be addressed

We describe studies to assess the influence of polymorphism in the human glutathione S-transferase GSTM3 gene on susceptibility to high grade astrocytoma. Immunohisto-chemical studies using a GSTM3-specific antiserum identified expression of the GSTM3 subunit in astrocytes. The relative levels of expression of GSTM1 and GSTM3 in brain cytosols were determined after resolution of these enzymes using chromatofocusing. We found no differences in the level of GSTM3 activity in individuals with GSTM1 null and those with GSTMl-positive genotypes (GSTM1 A, GSTM1 B and GSTM1 A/B). A case-control study was performed to determine if GSTM3 alone or in combination with GSTM1 or GSTT1 influenced susceptibility to high grade astrocytoma. After correction for differences in age and gender, GSTM3 AA was not significantly different in cases compared with controls. No significant interactions between GSTM3 AA and GSTM1 null were identified. The significant interaction between GSTM3 AA and GSTT1 null appeared to result from the strength of the main effect (GSTT1 null). The data show that while GSTM3 is expressed in astrocytes and contributes significantly to total GST activity in human brain, it does not appear to influence susceptibility to high grade astrocytoma. Further, unlike lung, there appears to be no relationship between the level of GSTM3 activity in brain and GSTM1 genotype.


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