SNPs in ultraconserved elements and familial breast cancer risk
SNPs in ultraconserved elements and familial breast cancer risk
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DOI：
10.1093/carcin/bgm290
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发表时间：
2008-02-01
期刊：
影响因子：
4.7
通讯作者：
Burwinkel, Barbara
中科院分区：
文献类型：
--
作者：
Yang, Rongxi;Frank, Bernd;Burwinkel, Barbara
超保守元件 (UCE) 是长度 >200 bp 的片段，显示人类、大鼠和小鼠基因组的直系同源区域之间的绝对序列同一性。影响这些 UCE 的选择因素仍然未知。最近的研究表明，UCE 充当侧翼基因的远程增强子，或者在与外显子重叠时参与剪接。 UCE 拷贝数变异的减少以及 UCE 内单核苷酸多态性 (SNP) 的显着不足也揭示了它们的进化和功能重要性，表明它们对癌症等疾病的潜在影响。在本研究中，我们研究了 UCE 中的 6 个 SNP 对家族性乳腺癌风险的影响。六个 SNP 中的两个显示与家族性乳腺癌风险相关。虽然 rs9572903 仅显示出临界显着关联，但病例中 rs2056116 的罕见 [G] 等位基因的频率高于对照组，表明家族性乳腺癌风险增加（[G] 与 [A]：比值比 (OR) = 1.18，95% 置信区间 (CI) 1.06-1.30，P = 0.0020；[GG] 与 [AA]：OR = 1.41，95% CI 1.15-1.74，P = 0.0011）。有趣的是，与较大年龄组相比，50 岁以下女性的 OR 有所增加（[G] 与 [A]：OR = 1.27，95% CI 1.11-1.45，P = 0.0005；[GG] 与 [AA]：OR = 1.60，95% CI 1.22-2.10，P = 0.0007），表明年龄-或激素相关的作用。这是第一项表明 UCE 中的 SNP 可能与癌症风险相关的研究。
Ultraconserved elements (UCEs) are segments of >200 bp length showing absolute sequence identity between orthologous regions of human, rat and mouse genomes. The selection factors acting on these UCEs are still unknown. Recent studies have shown that UCEs function as long-range enhancers of flanking genes or are involved in splicing when overlapping with exons. The depletion of UCEs among copy number variation as well as the significant under-representation of single-nucleotide polymorphisms (SNPs) within UCEs have also revealed their evolutional and functional importance indicating their potential impact on disease, such as cancer. In the present study, we investigated the influence of six SNPs within UCEs on familial breast cancer risk. Two out of six SNPs showed an association with familial breast cancer risk. Whereas rs9572903 showed only a borderline significant association, the frequency of the rare [G] allele of rs2056116 was higher in cases than in controls indicating an increased familial breast cancer risk ([G] versus [A]: odds ratio (OR) = 1.18, 95% confidence interval (CI) 1.06-1.30, P = 0.0020; [GG] versus [AA]: OR = 1.41, 95% CI 1.15-1.74, P = 0.0011). Interestingly, comparing with the older age group, the ORs were increased in woman younger than 50 years of age ([G] versus [A]: OR = 1.27, 95% CI 1.11-1.45, P = 0.0005; [GG] versus [AA]: OR = 1.60, 95% CI 1.22-2.10, P = 0.0007) pointing to an age- or hormone-related effect. This is the first study indicating that SNPs in UCEs might be associated with cancer risk.