Genetic variants in the TEP1 gene are associated with prostate cancer risk and recurrence.
Abstract
BACKGROUND: Telomere-related genes play an important role in carcinogenesis and progression
of prostate cancer (PCa). It is not fully understood whether genetic variations in
telomere-related genes are associated with development and progression in PCa patients.
METHODS: Six potentially functional single-nucleotide polymorphisms (SNPs) of three
key telomere-related genes were evaluated in 1015 PCa cases and 1052 cancer-free controls,
to test their associations with risk of PCa. Among 426 PCa patients who underwent
radical prostatectomy (RP), the prognostic significance of the studied SNPs on biochemical
recurrence (BCR) was also assessed using the Kaplan-Meier analysis and Cox proportional
hazards regression model. The relative telomere lengths (RTLs) were measured in peripheral
blood leukocytes using real-time PCR in the RP patients. RESULTS: TEP1 rs1760904 AG/AA
genotypes were significantly associated with a decreased risk of PCa (odds ratio (OR):
0.77, 95% confidence interval (CI): 0.64-0.93, P=0.005) compared with the GG genotype.
By using median RTL as a cutoff level, RP patients with TEP1 rs1760904 AG/AA genotypes
tended to have a longer RTL than those with the GG genotype (OR: 1.55, 95% CI: 1.04-2.30,
P=0.031). A significant interaction between TEP1 rs1713418 and age in modifying PCa
risk was observed (P=0.005). After adjustment for clinicopathologic risk factors,
the presence of heterozygotes or rare homozygotes of TEP1 rs1760904 and TNKS2 rs1539042
were associated with BCR in the RP cohorts (hazard ratio: 0.53, 95% CI: 0.36-0.79,
P=0.002 and hazard ratio: 1.67, 95% CI: 1.07-2.48, P=0.017, respectively). CONCLUSIONS:
These data suggest that genetic variations in the TEP1 gene may be biomarkers for
risk of PCa and BCR after RP.
Type
Journal articleSubject
AdultAged
Aged, 80 and over
Alleles
Carrier Proteins
Case-Control Studies
Gene Expression Regulation, Neoplastic
Gene Frequency
Genetic Predisposition to Disease
Genetic Variation
Genotype
Humans
Male
Middle Aged
Neoplasm Grading
Neoplasm Recurrence, Local
Neoplasm Staging
Polymorphism, Single Nucleotide
Prognosis
Prostatic Neoplasms
Risk
Risk Factors
Tankyrases
Telomere
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https://hdl.handle.net/10161/10664Published Version (Please cite this version)
10.1038/pcan.2015.27Publication Info
Gu, C; Li, Q; Zhu, Y; Qu, Y; Zhang, G; Wang, M; ... Ye, D (2015). Genetic variants in the TEP1 gene are associated with prostate cancer risk and recurrence.
Prostate Cancer Prostatic Dis, 18(4). pp. 310-316. 10.1038/pcan.2015.27. Retrieved from https://hdl.handle.net/10161/10664.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Qingyi Wei
Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director
for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology
and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally
recognized epidemiologist focused on the molecular and genetic epidemiology of head
and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and
genetic determinants for the DNA repair deficient phenotype and

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