Gra Olga A, Glotov Andrey S, Nikitin Eugene A, Glotov Oleg S, Kuznetsova Viktoria E, Chudinov Alexander V, Sudarikov Andrey B, Nasedkina Tatyana V
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Am J Hematol. 2008 Apr;83(4):279-87. doi: 10.1002/ajh.21113.
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.
编码异生物质代谢酶的基因多态性被视为改变癌症易感性的风险因素。我们开发了一种生物芯片，用于分析代谢系统10个基因中的18种突变：CYP1A1、CYP2D6、GSTT1、GSTM1、MTHFR、MTRR、NQO1、CYP2C9、CYP2C19和NAT2。利用生物芯片上的等位基因特异性杂交技术，对76例T细胞非霍奇金淋巴瘤（NHL）患者、83例B细胞慢性淋巴细胞白血病（B-CLL）患者和177名健康供者进行了检测。与正常对照相比，B-CLL患者中多态性CYP1A1等位基因更为常见，例如，多态性变体4887C>A、4889A>G和6235T>C的组合（OR=1.76，95%CI=1.0-3.1）。与对照相比，NHL患者中GSTM1无效基因型更为常见（OR=1.82，95%CI=1.1-3.1）。与对照相比，B-CLL患者中不利的多态性CYP1A1变体和GSTM1无效基因型的组合更为常见（OR=2.52，95%CI=1.3-4.9）。此外，男性B-CLL患者中CYP2C9基因杂合子和纯合子等位基因2的发生率显著增加（OR=2.38，95%CI=1.1-5.2），以及该基因等位基因2和*3的组合（OR=2.09，95%CI=1.1-3.9）。因此，我们的研究结果表明CYP1A1、GSTM1和CYP2C9基因的多态性等位基因与发生NHL或B-CLL的风险之间存在关联。所开发的生物芯片可被视为肿瘤血液学研究和预测分析的便捷分析工具。
