Sellick Gabrielle S, Catovsky Daniel, Houlston Richard S
Section of Cancer Genetics, Brooks Lawley Building, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
Leuk Res. 2006 Dec;30(12):1573-6. doi: 10.1016/j.leukres.2006.02.021. Epub 2006 Apr 3.
ARLTS1, a member of the Ras superfamily and putative tumor-suppressor gene resides at chromosome 13q14, a region commonly deleted in hematopoietic and solid tumors. Previously, the truncating single nucleotide polymorphism (SNP) of ARLTS, G446A (W149X) has been reported to act as a multi-site tumor susceptibility allele. To explore the relationship between polymorphic variation in ARTLS1 and risk of chronic lymphocytic leukemia (CLL) we analyzed germline DNA from 413 cases and 471 healthy controls for W149X and five additional coding SNPs, S99S, P131L, L132L, C148R, and E164K. A high proportion of the cases were familial, thereby empowering detection of an association. None of the SNPs were individually significantly associated with risk of CLL and there was no evidence for epistatic interaction between loci. Our study does not support the postulate that variants of ARLTS1 influence the risk of CLL.
ARLTS1是Ras超家族的成员，也是假定的肿瘤抑制基因，位于13号染色体q14区域，该区域在造血系统肿瘤和实体瘤中常发生缺失。此前，据报道ARLTS的截短型单核苷酸多态性（SNP），即G446A（W149X）可作为多位点肿瘤易感性等位基因。为了探究ARTLS1基因多态性变异与慢性淋巴细胞白血病（CLL）风险之间的关系，我们分析了413例CLL患者和471名健康对照者的生殖系DNA，检测其中的W149X以及另外五个编码SNP，即S99S、P131L、L132L、C148R和E164K。大部分病例为家族性病例，因此有利于检测两者之间的关联。没有一个SNP与CLL风险存在显著的个体相关性，并且没有证据表明这些位点之间存在上位性相互作用。我们的研究不支持ARLTS1基因变异会影响CLL风险这一假设。
