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Blood, Vol. 95 No. 4 (February 15), 2000:
pp. 1222-1228
Polymorphisms within glutathione S-transferase genes
(GSTM1, GSTT1, GSTP1) and risk of relapse in
childhood B-cell precursor acute lymphoblastic leukemia: a
case-control study
Martin Stanulla,
Martin Schrappe,
Annette
Müller Brechlin,
Martin Zimmermann, and
Karl Welte
From the Department of Pediatric Hematology and Oncology,
Children's Hospital, Hannover Medical School, Hannover, Germany.
Glutathione S-transferases (GSTs) have been associated with outcome
in human cancers treated with cytotoxic chemotherapy. In a case-control
study, we investigated the association between polymorphisms within the
GSTM1, GSTT1, and GSTP1 genes and risk of
relapse in childhood acute lymphoblastic leukemia (ALL). Cases were
relapsed patients. Controls were successfully treated patients with a
minimum follow-up of 5 years. The null genotype (absence of both
alleles) for GSTM1 or GSTT1 conferred a 2-fold
(OR = 0.5, 95% CI = 0.23-1.07, P = .078) and
2.8-fold (OR = 0.36, 95% CI = 0.13-0.99, P = .048)
reduction in risk of relapse, respectively, relative to the presence of
the GSTM1 or GSTT1 gene. The GSTP1 Val105/Val105 genotype showed a 3-fold decrease
in risk of relapse (OR = 0.33, 95% CI = 0.09-1.23,
P = .099) in comparison to the combined category of
Ile105/Val105 and
Ile105/Ile105 genotypes. No particular
associations with relapse were observed for the GSTP1
polymorphism at codon 114. The risk of relapse when having 1 of the
low-risk genotypes (GSTM1 null, GSTT1 null,
GSTP1 Val105/Val105) decreased 1.9-fold
(OR = 0.53, 95% CI = 0.24-1.19, P = .123), and the
risk when having 2 or 3 low-risk genotypes 3.5-fold (OR = 0.29,
95% CI = 0.06-1.37, P = .118), compared with
individuals having no low-risk genotype (P for
trend = .005). Our results suggest that polymorphisms within genes
of the GST superfamily may be associated with risk of relapse in
childhood ALL.
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