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

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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.

Olga A Gra, Andrey S Glotov, Eugene A Nikitin, Oleg S Glotov, Viktoria E

Kuznetsova, V Chudinov, Andrey B Sudarikov, and Tatyana V Nasedkina

Am J Hematol, December 5, 2007; .

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow,

Russia.

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. Am. J. Hematol.,

2008. © 2007 Wiley-Liss, Inc.

PMID: 18061941