Genetic polymorphisms of metabolic enzymes CYP1A1, CYP2D6, GSTM1 and GSTT1 and leukemia susceptibility.
The genetic polymorphisms of biotransformation phase I enzymes, cytochrome P450 (CYP1A1 and CYP2D6), and phase II enzymes, glutathione S-transferase (GSTM1 and GSTT1), were analyzed in 204 healthy persons and 348 leukemia patients, who suffered from also acute lymphoblastic leukemia (ALL), acute nonlymphoblastic leukemia (ANLL) chronic myelogenous leukemia (CML), from the Han ethnic group in Changsha City of Hunan Province of China. Our results showed that the frequencies of polymorphisms of CYP1A1, CYP2D6 and GSTT1 among the groups including acute lymphoblastic leukemia, ANLL, chronic myelogenous leukemia and healthy control have no significant differences. The variation of GSTM1-null genotype alone correlated with the development of ANLL. The combined genotypes of GSTM1-null with GSTT1-null, or GSTM1-null with CYP1A1 heterozygous mutant, or GSTM1-null with CYP1A1 heterozygous mutant and CYP2D6 heterozygous mutant, or GSTM1-null with CYP1A1 heterozygous mutant, CYP2D6 heterozygous mutant and GSTT1-null were found in individuals with high risk of ANLL. All these findings suggest that GSTM1-null genotype alone or in coordination with the relevant genotypes of other metabolic enzymes might be susceptibility factors in the etiology of ANLL.
Chen
Han-Chun
HC
Department of Biochemistry, School of Biological Science and Technology, Central South University, Changsha, Hunan, China. chenhanchun@hotmail.com
Hu
Wei-Xin
WX
Liu
Qing-Xia
QX
Li
Wen-Kai
WK
Chen
Fang-Zhi
FZ
Rao
Zhou-Zhou
ZZ
Liu
Xin-Fa
XF
Luo
Ya-Ping
YP
Cao
Yan-Fei
YF
D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1