ATM-BRCA2-CHEK2轴上的变异易引发慢性淋巴细胞白血病。
Variants in the ATM-BRCA2-CHEK2 axis predispose to chronic lymphocytic leukemia.
作者信息
Rudd Matthew F, Sellick Gabrielle S, Webb Emily L, Catovsky Daniel, Houlston Richard S
机构信息
Sections of Cancer Genetics and Haemato-Oncology, Institute of Cancer Research, Sutton, Surrey, UK.
出版信息
Blood. 2006 Jul 15;108(2):638-44. doi: 10.1182/blood-2005-12-5022. Epub 2006 Mar 30.
We conducted a large-scale association study to identify low-penetrance susceptibility alleles for chronic lymphocytic leukemia (CLL), analyzing 992 patients and 2707 healthy controls. To increase the likelihood of identifying disease-causing alleles we genotyped 1467 coding nonsynonymous single nucleotide polymorphisms (nsSNPs) in 865 candidate cancer genes, biasing nsSNP selection toward those predicted to be deleterious. Preeminent associations were identified in SNPs mapping to genes pivotal in the DNA damage-response and cell-cycle pathways, including ATM F858L (odds ratio [OR] = 2.28, P < .0001) and P1054R (OR = 1.68, P = .0006), CHEK2 I157T (OR = 14.83, P = .0008), BRCA2 N372H (OR = 1.45, P = .0032), and BUB1B Q349R (OR = 1.42, P = .0038). Our findings implicate variants in the ATM-BRCA2-CHEK2 DNA damage-response axis with risk of CLL.
我们开展了一项大规模关联研究，以确定慢性淋巴细胞白血病（CLL）的低 penetrance 易感性等位基因，分析了 992 例患者和 2707 名健康对照。为了增加识别致病等位基因的可能性，我们对 865 个候选癌症基因中的 1467 个编码非同义单核苷酸多态性（nsSNP）进行了基因分型，将 nsSNP 选择偏向于那些预测为有害的基因。在映射到 DNA 损伤反应和细胞周期途径中关键基因的 SNPs 中发现了显著关联，包括 ATM F858L（优势比 [OR] = 2.28，P <.0001）和 P1054R（OR = 1.68，P =.0006）、CHEK2 I157T（OR = 14.83，P =.0008）、BRCA2 N372H（OR = 1.45，P =.0032）和 BUB1B Q349R（OR = 1.42，P =.0038）。我们的研究结果表明，ATM-BRCA2-CHEK2 DNA 损伤反应轴中的变异与 CLL 风险有关。
Zotero 插件