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Polymorphisms in xenobiotic-metabolizing genes and the risk of chronic lymphocytic leukemia and non-Hodgkin's lymphoma in adult Russian patients.
- Source :
-
American journal of hematology [Am J Hematol] 2008 Apr; Vol. 83 (4), pp. 279-87. - Publication Year :
- 2008
-
Abstract
- 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.<br /> ((c) 2007 Wiley-Liss, Inc.)
- Subjects :
- Adult
Alleles
Arylamine N-Acetyltransferase genetics
Carcinogens, Environmental pharmacokinetics
Cytochrome P-450 Enzyme System genetics
Female
Ferredoxin-NADP Reductase genetics
Genetic Predisposition to Disease
Glutathione Transferase genetics
Humans
Leukemia, Lymphocytic, Chronic, B-Cell epidemiology
Lymphoma, T-Cell epidemiology
Male
Methylenetetrahydrofolate Reductase (NADPH2) genetics
NAD(P)H Dehydrogenase (Quinone) genetics
Nucleic Acid Hybridization
Risk Factors
Russia epidemiology
Biotransformation genetics
Leukemia, Lymphocytic, Chronic, B-Cell genetics
Lymphoma, T-Cell genetics
Oligonucleotide Array Sequence Analysis
Xenobiotics pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1096-8652
- Volume :
- 83
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 18061941
- Full Text :
- https://doi.org/10.1002/ajh.21113