Polymorphisms in xenobiotic-metabolizing genes and the risk of chronic lymphocytic leukemia and non-Hodgkin's lymphoma in adult Russian patients

Am J Hematol. 2008 Apr;83(4):279-87. doi: 10.1002/ajh.21113.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Arylamine N-Acetyltransferase / genetics
  • Biotransformation / 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
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Lymphoma, T-Cell / epidemiology
  • Lymphoma, T-Cell / genetics*
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • Nucleic Acid Hybridization
  • Oligonucleotide Array Sequence Analysis*
  • Risk Factors
  • Russia / epidemiology
  • Xenobiotics / pharmacokinetics*

Substances

  • Carcinogens, Environmental
  • Xenobiotics
  • Cytochrome P-450 Enzyme System
  • methionine synthase reductase
  • Ferredoxin-NADP Reductase
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human
  • glutathione S-transferase T1
  • Glutathione Transferase