Glutathione S-transferase theta 1 gene deletion and risk of acute myeloid leukemia.
Individuals with a homozygous deletion of the glutathione S-transferase theta 1 (GSTT1) gene lack GSTT1 enzymatic detoxification of environmental carcinogens by conjugation with glutathione. The GSTT1 gene deletion has been associated with carcinogen-induced chromosomal changes in lymphocytes, and some but not all epidemiological evidence has suggested that the GSTT1 gene deletion may increase susceptibility to myelodysplasia. We conducted a case-control study to test whether individuals with an inherited homozygous deletion of the GSTT1 gene are at increased risk of acute myeloid leukemia (AML). The GSTT1 and GST mu 1 (GSTM1) genotypes were determined by PCR using lymphocyte or bone marrow DNA from 297 AML patients and 152 controls. AML patients were selected from Southwest Oncology Group clinical studies, and controls were identified by random digit dialing in Washington state. No association was observed between the GSTT1 gene deletion and AML [race-adjusted odds ratio (OR), 0.94; 95% confidence interval (CI), 0.55-1.60] or between the GSTM1 gene deletion and AML (race-adjusted OR, 1.26; 95% CI, 0.85-1.88). Patients with secondary AML had a slightly higher prevalence of the GSTT1 and GSTM1 gene deletions compared with de novo AML patients or controls, but this was consistent with chance. Exploratory analyses of AML cytogenetics suggested a few associations, i.e., between the GSTT1 gene deletion and trisomy 8, and between the GSTM1 gene deletion and non-8 trisomies or inv(16). These results do not support the hypothesis that the GSTT1 gene deletion is related to the incidence of AML.
Crump
C
C
Department of Epidemiology, University of Washington, Seattle 98195, USA. kccrump@u.washington.edu
Chen
C
C
Appelbaum
F R
FR
Kopecky
K J
KJ
Schwartz
S M
SM
Willman
C L
CL
Slovak
M L
ML
Weiss
N S
NS
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
C413545:glutathione S-transferase T1; D005982:Glutathione Transferase