Short rare hTERT-VNTR2-2nd alleles are associated with prostate cancer susceptibility and influence gene expression.
Short rare hTERT-VNTR2-2nd alleles are associated with prostate cancer susceptibility and influence gene expression.
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DOI：
10.1186/1471-2407-10-393
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发表时间：
2010-07-26
期刊：
影响因子：
3.8
通讯作者：
Leem SH
中科院分区：
文献类型：
--
作者：
Yoon SL;Jung SI;Do EJ;Lee SR;Lee SY;Chu IS;Kim WJ;Jung J;Kim CS;Cheon SH;Leem SH
人端粒酶逆转录酶（human telomerase reverse transcriptase，hTERT）基因含有5个可变数目串联重复序列（variable number tandem repeats，VNTR），以前的研究已经描述了hTERT-VNTR 2 -2nd的多态性。我们研究了hTERT-VNTR 2 -2nd的等位基因变异如何影响前列腺癌的易感性。使用来自421名无癌症男性对照和329名前列腺癌患者的DNA进行病例对照研究。此外，为了确定VNTR多态性是否具有功能性后果，我们检查了与这些VNTR连接并由细胞系中的hTERT启动子驱动的报告基因的转录水平。从这项研究中检测到三个新的罕见等位基因，其中两个仅在癌症受试者中发现。罕见hTERT-VNTR 2 -2nd等位基因与前列腺癌风险之间存在统计学显著相关性[OR，5.17; 95%置信区间（CI），1.09-24.43; P = 0.021]。此外，这些插入增强子区域的VNTR可以影响前列腺癌细胞系中hTERT的表达。这是第一项研究报告罕见的hTERT VNTR与前列腺癌易感性相关，并且VNTR可以诱导前列腺癌细胞系中hTERT启动子活性水平的提高。因此，hTERT-VNTR 2 -2nd基因座可能通过影响基因表达而作为前列腺癌风险的调节剂。
The hTERT (human telomerase reverse transcriptase) gene contains five variable number tandem repeats (VNTR) and previous studies have described polymorphisms for hTERT-VNTR2-2nd. We investigated how allelic variation in hTERT-VNTR2-2nd may affect susceptibility to prostate cancer. A case-control study was performed using DNA from 421 cancer-free male controls and 329 patients with prostate cancer. In addition, to determine whether the VNTR polymorphisms have a functional consequence, we examined the transcriptional levels of a reporter gene linked to these VNTRs and driven by the hTERT promoter in cell lines. Three new rare alleles were detected from this study, two of which were identified only in cancer subjects. A statistically significant association between rare hTERT-VNTR2-2nd alleles and risk of prostate cancer was observed [OR, 5.17; 95% confidence interval (CI), 1.09-24.43; P = 0.021]. Furthermore, the results indicated that these VNTRs inserted in the enhancer region could influence the expression of hTERT in prostate cancer cell lines. This is the first study to report that rare hTERT VNTRs are associated with prostate cancer predisposition and that the VNTRs can induce enhanced levels of hTERT promoter activity in prostate cancer cell lines. Thus, the hTERT-VNTR2-2nd locus may function as a modifier of prostate cancer risk by affecting gene expression.
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影响因子：
11.5
作者：
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