title: 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.
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: C
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Pathology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.|Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
authors.forename: L
authors.initials: L
authors.lastname: Jin
authors.affiliation: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.|Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: D
authors.initials: D
authors.lastname: Ye
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D016601:RNA-Binding Proteins; D012306:Risk; D012307:Risk Factors; D038501:Tankyrases / Q000235:genetics; D016615:Telomere / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D016601:RNA-Binding Proteins; D038501:Tankyrases; C104342:TEP1 protein, human; C437334:TNKS2 protein, human; C418109:TNKS protein, human