Polymorphisms in xenobiotic-metabolizing genes and the risk of chronic lymphocytic leukemia and non-Hodgkin's lymphoma in adult Russian patients
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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DOI：
10.1002/ajh.21113
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发表时间：
2008-04-01
影响因子：
12.8
通讯作者：
Nasedkina, Tatyana V.
中科院分区：
文献类型：
--
作者：
Gra, Olga A.;Glotov, Andrey S.;Nasedkina, Tatyana V.
编码异源代谢酶的基因的多态被认为是改变癌症易感性的危险因素。我们建立了一种芯片，用于分析代谢系统10个基因的18个突变：CYP1A1、CYP2D6、GSTT1、GSTM1、MTHFR、MTRR、NQO1、CYP2C9、CYP2C19和Nat2。应用血芯片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例健康献血员进行了检测。与正常对照组相比，B-CLL患者的CYP1A1等位基因频率更高，如4887C>；A、4889A>；G和6235T>；C等位基因组合(OR=1.76，95%CI=1.0~3.1)。NHL组GSTM1缺失型频率明显高于对照组(OR=1.82，95%CI=1.1~3.1)。B-CLL患者中存在CYP1A1基因突变和GSTM1缺失型的频率明显高于对照组(OR=2.52，95%CI=1.3~4.9)。此外，男性B-CLL患者的CYP2C9基因*2杂合子和纯合子的发生率显著增加(OR=2.38，95%CI=1.1~5.2)，以及该基因的*2和*3等位基因组合的发生率显著增加(OR=2.09，95%CI=1.1~3.9)。因此，我们的研究结果表明，CYP1A1、GSTM1和CYP2C9基因的多态等位基因与NHL或B-CLL的发病风险有关。所开发的生物芯片可被认为是肿瘤血液学研究和预测分析的便捷分析工具。
Polymorphisms in genes coding xenobiotic-metabolizing enzymes are considered as risk factors modifying susceptibility to cancer. We developed a blochip 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 blochip 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% Cl = 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.