Original Article | Published:

Basic Research

Genetic variants in the TEP1 gene are associated with prostate cancer risk and recurrence

Prostate Cancer and Prostatic Diseases volume 18, pages 310316 (2015) | Download Citation

Subjects

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.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (grant number 81272837) and Shanghai municipal hospital emerging advanced technology joint research project (grant number SHDC12013122). This study was supported by National Natural Science Foundation of China (grant number 81272837) and Shanghai municipal hospital emerging advanced technology joint research project (grant number SHDC12013122).

Author information

Author notes

    • C Gu
    • , Q Li
    •  & Y Zhu

    These authors contributed equally to this work.

Affiliations

  1. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China

    • C Gu
    • , Y Zhu
    • , Y Qu
    • , G Zhang
    •  & D Ye
  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    • C Gu
    • , Q Li
    • , Y Zhu
    • , Y Qu
    • , G Zhang
    • , M Wang
    •  & D Ye
  3. Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China

    • Q Li
    • , M Wang
    •  & Q Wei
  4. Department of Pathology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, China

    • Q Li
  5. Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China

    • Y Yang
    • , J Wang
    •  & L Jin
  6. Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China

    • Y Yang
    • , J Wang
    •  & L Jin
  7. Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA

    • Q Wei

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Competing interests

The authors declare no conflicts of interest.

Corresponding authors

Correspondence to Q Wei or D Ye.

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DOI

https://doi.org/10.1038/pcan.2015.27

Supplementary Information accompanies the paper on the Prostate Cancer and Prostatic Diseases website (http://www.nature.com/pcan)

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