Short rare hTERT-VNTR2-2nd alleles are associated with prostate cancer susceptibility and influence gene expression

BMC Cancer

Research Article

Se-Lyun Yoon¹  Se-Ra Lee¹  Eun-Ju Do¹  Sun-Hee Leem¹  Sang-Yeop Lee²  Choung Soo Kim³  Jaeil Jung⁴  Wun-Jae Kim⁵  Se-Il Jung⁶  Sang-Hyeon Cheon⁷  In-Sun Chu⁸ 

[1] Department of Biology and Biomedical Science, Dong-A University, Busan, South Korea;Department of Biology and Biomedical Science, Dong-A University, Busan, South Korea;Korean BioInformation Center, KRIBB, Daejeon, South Korea;Department of Urology, College of Medicine, Asan Medical Center, Ulsan University, Seoul, South Korea;Department of Urology, College of Medicine, Busan Paik Hospital, Inje University, Busan, South Korea;Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea;Department of Urology, College of Medicine, Dong-A University, Busan, South Korea;Department of Urology, College of Medicine, Ulsan University Hospital, Ulsan University, Ulsan, South Korea;Korean BioInformation Center, KRIBB, Daejeon, South Korea;

关键词: Prostate Cancer;    Prostate Cancer Patient;    LNCap Cell;    Rare Allele;    Prostate Cancer Cell Line;   

DOI  :  10.1186/1471-2407-10-393

 received in 2010-03-04, accepted in 2010-07-26,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsA 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.ResultsThree 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.ConclusionsThis 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.

【 授权许可】

Unknown   
© Yoon et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.