Short rare hTERT-VNTR2-2nd alleles are associated with prostate cancer susceptibility and influence gene expression
1 Department of Biology and Biomedical Science, Dong-A University, Busan, South Korea
2 Department of Urology, College of Medicine, Dong-A University, Busan, South Korea
3 Korean BioInformation Center, KRIBB, Daejeon, South Korea
4 Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea
5 Department of Urology, College of Medicine, Busan Paik Hospital, Inje University, Busan, South Korea
6 Department of Urology, College of Medicine, Asan Medical Center, Ulsan University, Seoul, Korea
7 Department of Urology, College of Medicine, Ulsan University Hospital, Ulsan University, Ulsan, South Korea
BMC Cancer 2010, 10:393 doi:10.1186/1471-2407-10-393Published: 26 July 2010
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.