ALLELISM AT THE GLUTATHIONE-S-TRANSFERASE GSTM3 LOCUS - INTERACTIONS WITH GSTM1 AND GSTT1 AS RISK-FACTORS FOR ASTROCYTOMA

We describe studies to assess the influence of polymorphism in the hum an glutathione S-transferase GSTM3 gene on susceptibility to high grad e astrocytoma, Immunohistochemical studies using a GSTM3-specific anti serum identified expression of the GSTM3 subunit in astrocytes, The re lative levels of expression of GSTM1 and GSTM3 in brain cytosols were determined after resolution of these enzymes using chromatofocusing, W e found no differences in the level of GSTM3 activity in individuals w ith GSTM1 null and those with GSTM1-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 susceptib ility to high grade astrocytoma, After correction for differences in a ge and gender, GSTM3 AA was not significantly different in cases compa red with controls, No significant interactions between GSTM3 AA and GS TM1 null were identified, The significant interaction between GSTM3 AA and GSTT1 null appeared to result from the strength of the main effec t (GSTT1 null), The data show that while GSTM3 is expressed in astrocy tes and contributes significantly to total GST activity in human brain , it does not appear to influence susceptibility to high grade astrocy toma, Further, unlike lung, there appears to be no relationship betwee n the level of GSTM3 activity in brain and GSTM1 genotype.