Association of genetic polymorphisms in the telomerase reverse transcriptase gene with prostate cancer aggressiveness.
Telomerase reverse transcriptase (TERT), encoded by the TERT gene, is an essential component of telomerase, essential for the maintenance of telomere DNA length, chromosomal stability and cellular immortality. The aim of the present study was to evaluate the association between common genetic variations across the TERT gene region and prostate cancer (PCa) aggressiveness in a Chinese population. A total of 12 TERT tagging single-nucleotide polymorphisms (SNPs) were genotyped on the Sequenom Mass-ARRAY iPLEX® platform in a case-case study with 1,210 Chinese patients with PCa. Unconditional logistic regression was used to investigate the association of genotypes with PCa aggressiveness, Gleason grade and risk of developing early-onset PCa. It was observed that the C allele of the TERT intron 2 SNP (rs2736100) was significantly associated with reduced risk of PCa aggressiveness [odds ratio (OR)=0.81; 95% confidence interval (CI): 0.66-0.99; P=0.037]. This allele was also significantly correlated with a reduced risk of developing a tumor with a high Gleason score (>7; OR=0.83; 95% CI: 0.70-0.99; P=0.039). The T allele of the intron 4 SNP (rs10069690) was found to be significantly associated with a decreased risk for an aggressive form of PCa (OR=0.76; 95% CI: 0.59-0.97; P=0.030). In addition, the A allele of rs10078761 located at the 3' end of the TERT gene exhibited a statistically significant association with the reduced risk of developing a higher grade disease (OR=0.48; 95% CI: 0.28-0.81; P=0.006). However, no association between TERT polymorphisms and age at diagnosis was observed in the present study. The present findings demonstrated for the first time, to the best of our knowledge, that genetic variations across the TERT gene are associated with PCa aggressiveness in a Chinese Han population.
Department of Urology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
Dapeng
D
Wu
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China.
Hongjie
H
Yu
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston‑Salem, NC 27157, USA.
Jielin
J
Sun
Department of Urology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
Jun
J
Qi
Department of Urology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
Qiang
Q
Liu
Department of Urology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
Ruipeng
R
Li
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston‑Salem, NC 27157, USA.
Siqun Lily
SL
Zheng
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China.
Jianfeng
J
Xu
Department of Urology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
Jian
J
Kang
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics*
D019098:Telomerase