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Higher frequency of glutathione S-transferase deletions in black children
with acute lymphoblastic leukemia
CL Chen, Q Liu, CH Pui, GK Rivera, JT Sandlund, R Ribeiro, WE Evans and MV Relling
Department of Pharmaceutical Sciences, St Jude Children's Research
Hospital, Memphis, TN 38101, USA.
The genetic polymorphisms in human glutathione S-transferases (GST) M1 and
T1 have been associated with race, disease risk, and outcome of some 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 in 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 patients were GSTM1
null, frequencies not significantly different (P = .19) than healthy
controls (53.5% in whites and 27.6% in blacks), although there was a trend
toward more null genotypes in black ALL patients. 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 case in white patients with ALL (10 of 163
or 6.1%) compared to white controls (8.0%) (P = .68). In stratified
analyses, the GST double-null genotype was not associated with other
characteristics that might differ between whites and blacks with ALL, such
as age, T-lineage immunophenotype, presenting white blood cell count, DNA
index, or insurance status. The null genotype for GSTM1, GSTT1, or both was
not found to be a prognostic factor for disease-free survival or
probability of hematologic remission; central nervous system relapse tended
to be less common in those with the GSTM1 null genotype (P = .054). The
double-null genotype 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 childhood ALL in American blacks.
Volume 89,
Issue 5,
pp. 1701-1707,
03/01/1997
Copyright © 1997 by The American Society of Hematology
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