A functional promoter polymorphism in the TERT gene does not affect inherited susceptibility to breast cancer
A functional promoter polymorphism in the TERT gene does not affect inherited susceptibility to breast cancer
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DOI：
10.1016/j.cancergencyto.2008.12.006
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发表时间：
2009-04-15
影响因子：
--
通讯作者：
Forsti, Asta
中科院分区：
文献类型：
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作者：
Varadi, Verena;Brendle, Annika;Forsti, Asta
端粒功能障碍是癌症发展的关键机制。人类端粒酶逆转录酶 (TERT) 是端粒酶的限速催化亚基，对于维持端粒 DNA 长度、染色体稳定性和细胞永生至关重要。在我们试图鉴定 TERT 基因的功能多态性及其对乳腺癌风险的影响时，我们对该基因的启动子进行了测序，并鉴定了三个频率至少为 10% 的单核苷酸多态性 (SNP)。其中一个 SNP，rs2853669 (-244 T > C)，已被证明会影响端粒酶活性和端粒长度。最近，该 SNP 被认为会影响家族性乳腺癌风险。在我们的病例对照研究中，使用了两个大型乳腺癌样本系列，其中一个包含 841 例具有乳腺癌遗传易感性的病例。我们没有发现与家族性或散发性乳腺癌风险有任何关联。这项强有力的研究排除了功能性 -244 T > C SNP 和其他两个相关 SNP 对乳腺癌风险的影响。 (c) 2009 Elsevier Inc. 保留所有权利。
Telomere dysfunction is a key mechanism in cancer development. The human telomerase reverse transcriptase (TERT) is the rate-limiting catalytic subunit of the telomerase enzyme, which is necessary for the maintenance of telomere DNA length, chromosomal stability, and cellular immortality In our attempt to identify functional polymorphisms in the TERT gene and their effect oil breast cancer risk, we sequenced the promoter of the gene and identified three single nucleotide polymorphisms (SNPs) with a frequency of at least 10%. One of these SNPs, rs2853669 (-244 T > C), has been shown to affect telomerase activity and telomere length. Recently, this SNP has been suggested to affect familial breast cancer risk. In our case-control study using two large breast cancer sample series, including one with 841 cases with inherited susceptibility to breast cancer. we did not find any association with familial or sporadic breast cancer risk. This well-powered study excludes an effect of the functional -244 T > C SNP and two other correlated SNPs on breast cancer risk. (c) 2009 Elsevier Inc. All rights reserved.