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.

Molecular Markers of Telomerase Complex for Patients with Pituitary Adenoma

“…It should be noted that genetic variants that affect telomere length, telomerase activation, and telomeric protein configuration may cause functional changes responsible for cancer development and further tumor growth. Cancer Genome Association Studies have shown that single-nucleotide polymorphisms (SNPs) in telomere-associated genes are associated with a risk of developing various tumors [ 20 ]. In the literature on the selected polymorphisms, only a possible association with tumors of other localizations has been described [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

Genetic variants in telomere‐maintenance genes are associated with ovarian cancer risk and outcome

“…TEP1 (telomerase‐associated protein 1, 14q11.2) gene product is a component of the telomerase enzyme complex . TEP1 SNPs have been associated with the risks of bladder , stomach , prostate , and breast cancer , the prognosis of liver and prostate cancer , and the risk of type 2 diabetes . Although TEP1 is a telomerase‐binding protein, previously it was shown that TEP1 is not essential for telomerase activity or telomere length maintenance in a mouse model .…”

Association of PINX1 but not TEP1 Polymorphisms with Progression to Hepatocellular Carcinoma in Thai Patients with Chronic Hepatitis B Virus Infection

“…Irregular function of this protein resulting from unbalanced gene expression or genetic variation may affect genome and chromosomal stability and promote cancer development. Previous findings of TEP1 polymorphisms were reported in many cancers such as prostate cancer (Gu et al, 2015), breast cancer (Varadi et al, 2009) and bladder cancer (Chang et al, 2012) as well as in male infertility (Yan et al, 2014). Recent study in Korea cohorts demonstrated that TEP1 polymorphisms were associated with risk of HCC, especially in rs1713449 by using high-throughput SNPs genotyping assay (Jung et al, 2014).…”