Raskin Leon, Rennert Gad, Gruber Stephen B
Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Cancer Genet Cytogenet. 2009 Apr 1;190(1):40-2. doi: 10.1016/j.cancergencyto.2008.12.005.
Recent studies have characterized X-linked transcriptional regulator FOXP3 as a tumor suppressor gene involved in the pathogenesis of breast cancer. A high rate of somatic FOXP3 mutations in breast tumors and the consequent upregulation of ERBB2 (alias HER-2) make FOXP3 a good candidate gene for breast cancer susceptibility. By taking advantage of a highly conserved FOXP3 sequence, we genotyped three haplotype-tagging single-nucleotide polymorphisms (htSNPs) that cover 40kb around the FOXP3 gene region in 1,529 cases and 1,528 controls from the large population-based Genetic Epidemiology Breast Cancer (GEBC) study in northern Israel. None of the FOXP3 htSNPs showed strong association with breast cancer risk. There was no evidence for significant heterogeneity by ethnicity (Ashkenazi Jews, Sephardic Jews, Arabs), first-degree family history of breast cancer, or age at diagnosis in stratified analysis. The analysis of reconstructed haplotypes based on the three FOXP3 htSNPs did not identify any haplotypes associated with breast cancer. Although FOXP3 is a biologically relevant gene in the pathogenesis of breast cancer, germline variation was not meaningfully associated with risk of the disease.
近期研究已将X连锁转录调节因子FOXP3鉴定为一种参与乳腺癌发病机制的肿瘤抑制基因。乳腺肿瘤中体细胞FOXP3突变率较高，以及由此导致的ERBB2（别名HER-2）上调，使FOXP3成为乳腺癌易感性的一个良好候选基因。利用高度保守的FOXP3序列，我们对来自以色列北部基于人群的大型遗传流行病学乳腺癌（GEBC）研究中的1529例病例和1528例对照，对覆盖FOXP3基因区域周围40kb的三个单倍型标签单核苷酸多态性（htSNP）进行了基因分型。FOXP3的htSNP均未显示与乳腺癌风险有强关联。在分层分析中，没有证据表明按种族（阿什肯纳兹犹太人、西班牙裔犹太人、阿拉伯人）、乳腺癌一级家族史或诊断年龄存在显著异质性。基于三个FOXP3 htSNP对重建单倍型的分析未发现与乳腺癌相关的任何单倍型。虽然FOXP3在乳腺癌发病机制中是一个生物学相关基因，但种系变异与该疾病风险无显著关联。
