Polymorphisms in xenobiotic-metabolizing genes and the risk of chronic lymphocytic leukemia and non-Hodgkin's lymphoma in adult Russian patients
| Autor: | V. E. Kuznetsova, Eugene Nikitin, Tatyana V. Nasedkina, Alexander V. Chudinov, Oleg S. Glotov, Andrey Sudarikov, O. A. Gra, Andrey S. Glotov |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male medicine.medical_specialty Arylamine N-Acetyltransferase Chronic lymphocytic leukemia Lymphoma T-Cell Russia Xenobiotics Cytochrome P-450 Enzyme System Risk Factors hemic and lymphatic diseases Internal medicine Genotype NAD(P)H Dehydrogenase (Quinone) medicine Humans Genetic Predisposition to Disease Allele Alleles Biotransformation Methylenetetrahydrofolate Reductase (NADPH2) Glutathione Transferase Oligonucleotide Array Sequence Analysis Hematology biology Nucleic Acid Hybridization medicine.disease Leukemia Lymphocytic Chronic B-Cell MTRR Carcinogens Environmental Non-Hodgkin's lymphoma Lymphoma Ferredoxin-NADP Reductase Methylenetetrahydrofolate reductase Immunology biology.protein Female |
| Zdroj: | American Journal of Hematology. 83:279-287 |
| ISSN: | 1096-8652 0361-8609 |
| Popis: | 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 5 1.76, 95% CI 5 1.0‐3.1). The GSTM1 null genotype was more frequent in NHL patients relative to controls (OR 5 1.82, 95% CI 5 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 5 2.52, 95% CI 5 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 5 2.38, 95% CI 5 1.1‐5.2) as well as a combination of alleles *2 and *3 of the gene (OR 5 2.09, 95% CI 5 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. Am. J. Hematol. 00:000‐000, 2007. V C 2007 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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