Exploring the association between genetic variation in the SUMO isopeptidase gene USPL1 and breast cancer through integration of data from the population-based GENICA study and external genetic databases
Exploring the association between genetic variation in the SUMO isopeptidase gene USPL1 and breast cancer through integration of data from the population-based GENICA study and external genetic databases
复制标题
DOI：
10.1002/ijc.28040
复制
发表时间：
2013-07-15
影响因子：
6.4
通讯作者：
Hamann, Ute
中科院分区：
文献类型：
--
作者：
Bermejo, Justo Lorenzo;Kabisch, Maria;Hamann, Ute
小泛素样修饰物（SUMO）蛋白共价连接到靶蛋白以修饰其功能。SUMO结合参与与肿瘤发生密切相关的过程。最近USPL 1（泛素特异性肽酶样（1））被鉴定为SUMO异肽酶。我们在这里报告了第一个探索性研究，调查USPL 1遗传变异与乳腺癌之间的关系。在基于人群的GENICA研究的1,021例乳腺癌病例和1,015例对照中，对三种潜在功能性非同义编码SNP（rs3742303、rs 17609459、rs7984952）进行了基因分型。我们利用基于HapMap和千人基因组计划数据的多基因型插补来改进所调查地区的关联筛选。公共遗传数据库还用于研究USPL 1在淋巴母细胞系和乳腺组织中表达的关系。与TT纯合子相比，rs7984952次要C等位基因纯合子女性发生3级乳腺肿瘤的风险较低（OR 0.50，95% CI 0.30-0.81）。仅病例分析证实了rs7984952与肿瘤分级之间的相关性（OR 0.60，95% CI 0.39-0.93）。基于HapMap和1000 Genomes Project数据的rs7984952周围238 kb区域的插补结果相似。没有插补变异显示出比rs7984952更强的关联信号。USPL 1在乳腺癌组织中的表达随着C等位基因数目的增加而增加。本研究说明了使用公共数据库对标准基因分型实验室进行基因型多重插补的贡献。所提供的信息可能有助于设计独立研究，以验证USPL 1 rs7984952与3级乳腺肿瘤风险之间的相关性。
Small ubiquitin-like modifier (SUMO) proteins are covalently attached to target proteins to modify their function. SUMO conjugation participates in processes tightly linked to tumorigenesis. Recently USPL1 (ubiquitin-specific peptidase-like (1) was identified as a SUMO isopeptidase. We report here on the first exploratory study investigating the relationship between genetic variability in USPL1 and breast cancer. Three potentially functional nonsynonymous coding SNPs (rs3742303, rs17609459, rs7984952) were genotyped in 1,021 breast cancer cases and 1,015 controls from the population-based GENICA study. We took advantage of multiple genotype imputation based on HapMap and the 1000 Genomes Project data to refine the association screening in the investigated region. Public genetic databases were also used to investigate the relationship with USPL1 expression in lymphoblastoid cell lines and breast tissue. Women homozygous for the minor C allele of rs7984952 showed a lower risk of Grade 3 breast tumors compared to TT homozygotes (OR 0.50, 95% CI 0.30-0.81). Case-only analyses confirmed the association between rs7984952 and tumor grade (OR 0.60, 95% CI 0.39-0.93). Imputation results in a 238 kb region around rs7984952 based on HapMap and the 1000 Genomes Project data were similar. No imputed variant showed an association signal stronger than rs7984952. USPL1 expression in tumor breast tissue increased with the number of C alleles. The present study illustrates the contribution of multiple imputation of genotypes using public data repositories to standard genotyping laboratory. The provided information may facilitate the design of independent studies to validate the association between USPL1 rs7984952 and risk of Grade 3 breast tumors.