Polymorphisms in xenobiotic-metabolizing genes and the risk of chronic lymphocytic leukemia and non-Hodgkin's lymphoma in adult Russian patients.
Polymorphisms in genes coding xenobiotic-metabolizing enzymes are considered as risk factors modifying susceptibility to cancer. We developed a biochip for the analysis of 18 mutations in 10 genes of metabolizing system: CYP1A1, CYP2D6, GSTT1, GSTM1, MTHFR, MTRR, NQO1, CYP2C9, CYP2C19, and NAT2. Using allele-specific hybridization on the biochip 76 T-cell non-Hodgkin's lymphoma (NHL) patients, 83 B-cell chronic lymphocytic leukemia (B-CLL) patients, and 177 healthy donors were tested. Polymorphic CYP1A1 alleles were more frequent in B-CLL patients relative to normal controls, for example, a combination of polymorphic variants 4887C > A, 4889A > G, and 6235T > C (OR = 1.76, 95% CI = 1.0-3.1). The GSTM1 null genotype was more frequent in NHL patients relative to controls (OR = 1.82, 95% CI = 1.1-3.1). The combination of unfavorable polymorphic CYP1A1 variants and GSTM1 null genotype was found more frequently in B-CLL patients relative to controls (OR = 2.52, 95% CI = 1.3-4.9). In addition, male B-CLL patients demonstrated a significantly increased occurrence of heterozygous and homozygous allele *2 of CYP2C9 gene (OR = 2.38, 95% CI = 1.1-5.2) as well as a combination of alleles *2 and *3 of the gene (OR = 2.09, 95% CI = 1.1-3.9). Thus, our findings show the association between polymorphic alleles of CYP1A1, GSTM1, and CYP2C9 genes and the risk to develop NHL or B-CLL. The developed biochip can be considered as a convenient analytical tool for research studies and predictive analysis in oncohematology.
Gra
Olga A
OA
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Glotov
Andrey S
AS
Nikitin
Eugene A
EA
Glotov
Oleg S
OS
Kuznetsova
Viktoria E
VE
Chudinov
Alexander V
AV
Sudarikov
Andrey B
AB
Nasedkina
Tatyana V
TV
D000328:Adult; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D001711:Biotransformation / Q000235:genetics*; D002274:Carcinogens, Environmental / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000453:epidemiology / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D012307:Risk Factors; D012426:Russia / Q000453:epidemiology; D015262:Xenobiotics / Q000493:pharmacokinetics*
D002274:Carcinogens, Environmental; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase