Polymorphisms of CYP1A1 and glutathione S-transferase and susceptibility to adult acute myeloid leukemia.
OBJECTIVE
The origin of acute myeloid leukemia (AML) may be explained by a combination of genetic susceptibility factors and environmental exposure. We studied the polymorphisms of cytochrome P450 CYP1A1 and glutathione S-transferase (GST), enzymes involved in the metabolism of carcinogens and anti-cancer drugs, as risk factors for adult AML.


METHODS
The prevalence of CYP1A1*2A, *2B and *4 alleles and of GSTM1 and GSTT1 homozygous deletions was examined in 193 patients with AML and 273 normal individuals using polymerase chain reaction (PCR)-based methods.


RESULTS
A higher prevalence of the CYP1A1*4 allele was found in AML patients than in controls (19.1% vs 9.9%, OR =2.2, 95% C.I. 1.3-3.7, p=0.006). GSTT1 homozygous deletions were also more frequent in AML patients (29% vs 19%, OR = 1.7, 95% CI 1.1-2.7, p=0.02). The combination of GSTT1 null genotype and CYP1A1 *2B and *4 alleles further increased the risk of AML (OR =10.2, 95% CI 1.2-83.9, p=0.01, and OR =7.0, 95% CI 2.0-24.8, p=0.001, respectively).


CONCLUSIONS
Polymorphic variants in xenobiotic-metabolism genes, including CYP1A1 and GSTT1, may increase the risk of adult AML, particularly when present together.
D'Alò
Francesco
F
Istituto di Ematologia, Universita' Cattolica S. Cuore, Rome, Italy.
Voso
Maria Teresa
MT
Guidi
Francesco
F
Massini
Giuseppina
G
Scardocci
Alessandra
A
Sica
Simona
S
Pagano
Livio
L
Hohaus
Stefan
S
Leone
Giuseppe
G
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors
D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase