HIGHER FREQUENCY OF GLUTATHIONE-S-TRANSFERASE DELETIONS IN BLACK-CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA

The genetic polymorphisms in human glutathione S-transferases (GST) M1 and T1 have been associated with race, disease risk, and outcome of s ome adult cancers. Also, there are racial differences in the incidence and characteristics of childhood acute lymphoblastic leukemia (ALL). Our objectives were to compare the frequency of the null genotype for GSTM1, GSTT1, or both in children with ALL to that in healthy controls , and to determine whether GST genotype was associated with treatment outcome and prognostic factors. We studied GSTM1 and GSTT1 genotypes i n somatic cell DNA from black children and white children with ALL and in 416 healthy controls, using a polymerase chain reaction technique. Ninety of 163 (55.2%) white ALL patients and 14 of 34 (41.2%) black p atients were GSTM1 null, frequencies not significantly different (P = .19) than healthy controls (53.5% in whites and 27.6% in blacks), alth ough there was a trend toward more null genotypes in black ALL patient s. Twenty-three of 163 (14.1%) white ALL patients and 12 of 34 (35.3%) black ALL patients were GSTT1 null, not different (P = .34) than the frequencies in healthy controls (15.0% in whites and 24.1% in blacks). However, the frequency of the ''double-null'' genotype, lacking both GSTM1 and GSTT1, was higher in black patients with ALL (8 of 34 or 23. 5%) than in black controls (3.9%) (P = .0005), but this was not the ca se in white patients with ALL (10 of 163 or 6.1%) compared to white co ntrols (8.0%) (P = .68). In stratified analyses, the GST double-null g enotype was not associated with other characteristics that might diffe r between whites and blacks with ALL, such as age, T-lineage immunophe notype, presenting white blood cell count, DNA index, or insurance sta tus. The null genotype for GSTM1, GSTT1, or both was not found to be a prognostic factor for disease-free survival or probability of hematol ogic remission; central nervous system relapse tended to be less commo n in those with the GSTM1 null genotype (P = .054). The double-null ge notype for GSTM1 and GSTT1 is more common among blacks but not whites with childhood ALL. These data suggest that GST genotype, coupled with unidentified additional risk factors, may play a role in risk of chil dhood ALL in American blacks. (C) 1997 by The American Society of Hema tology.