Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Basic Research

Association between lncrna PCGEM1 polymorphisms and prostate cancer risk

Abstract

Background:

Prostate cancer (PCa) gene expression marker 1 (PCGEM1), a long noncoding RNA, has drawn increasing attention for its important role in PCa. However, the association between genetic variations in the PCGEM1 gene and risk of PCa has not been investigated yet.

Methods:

We investigated the effect of two tagging single-nucleotide polymorphism (tSNPs; rs6434568 and rs16834898) in PCGEM1 gene on PCa risk in the Chinese men. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association.

Results:

We found a significantly decreased risk of PCa for rs6434568 AC and AC/AA genotype (adjusted OR=0.76, 95% CI=0.60–0.97 for AC; adjusted OR=0.76, 95% CI=0.61–0.96 for AC/AA), as well as rs16834898 AC and AC/CC genotype (adjusted OR=0.76, 95% CI=0.59–0.97 for AC; adjusted OR=0.79, 95% CI=0.62–0.99 for AC/CC), compared with the CC and AA genotypes, respectively. When we evaluated these two tSNPs together based on the risk alleles (that is, rs6434568 C and rs16834898 A), we found that the combined genotypes with four risk alleles were associated with an increased risk of PCa compared with those carrying 0–3 risk alleles (1.53, 1.19–1.97), and this increased risk was more pronounced among subjects of70 years (1.80, 1.24–2.62), Gleason score7 (1.68, 1.28–2.22) and PSA level20 (1.64, 1.24–2.18).

Conclusions:

Our results indicated that PCGEM1 polymorphisms may contribute to PCa risk in Chinese men. Additional functional analyses are required to detect the detailed mechanism underlying the observed association.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Siegel R, Naishadham D, Jemal A . Cancer statistics, 2012. CA Cancer J Clin 2012; 62: 10–29.

    Article  PubMed  Google Scholar 

  2. Jian L, Xie LP, Lee AH, Binns CW . Protective effect of green tea against prostate cancer: a case-control study in southeast China. Int J Cancer 2004; 108: 130–135.

    Article  CAS  PubMed  Google Scholar 

  3. Shao Q, Ouyang J, Fan Y, Xie J, Zhou J, Wu J et al. Prostate cancer in the senior men from rural areas in east district of China: contemporary management and 5-year outcomes at multi-institutional collaboration. Cancer Lett 2012; 315: 170–177.

    Article  CAS  PubMed  Google Scholar 

  4. Isaacs W, De Marzo A, Nelson WG . Focus on prostate cancer. Cancer Cell 2002; 2: 113–116.

    Article  CAS  PubMed  Google Scholar 

  5. Dianat SS, Margreiter M, Eckersberger E, Finkelstein J, Kuehas F, Herwig R et al. Gene polymorphisms and prostate cancer: the evidence. BJU Int 2009; 104: 1560–1572.

    Article  CAS  PubMed  Google Scholar 

  6. Moran VA, Perera RJ, Khalil AM . Emerging functional and mechanistic paradigms of mammalian long non-coding RNAs. Nucleic Acids Res 2012; 40: 6391–6400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mercer TR, Dinger ME, Mattick JS . Long non-coding RNAs: insights into functions. Nat Rev Genet 2009; 10: 155–159.

    Article  CAS  PubMed  Google Scholar 

  8. Costa FF . Non-coding RNAs: Meet thy masters. Bioessays 2010; 32: 599–608.

    Article  CAS  PubMed  Google Scholar 

  9. Wilusz JE, Sunwoo H, Spector DL . Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 2009; 23: 1494–1504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Huarte M, Rinn JL . Large non-coding RNAs: missing links in cancer? Hum Mol Genet 19: R152–R161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ifere GO, Ananaba GA . Prostate cancer gene expression marker 1 (PCGEM1): a patented prostate- specific non-coding gene and regulator of prostate cancer progression. Recent Pat DNA Gene Seq 2009; 3: 151–163.

    Article  CAS  PubMed  Google Scholar 

  12. Petrovics G, Zhang W, Makarem M, Street JP, Connelly R, Sun L et al. Elevated expression of PCGEM1, a prostate-specific gene with cell growth-promoting function, is associated with high-risk prostate cancer patients. Oncogene 2004; 23: 605–611.

    Article  CAS  PubMed  Google Scholar 

  13. Fu X, Ravindranath L, Tran N, Petrovics G, Srivastava S . Regulation of apoptosis by a prostate-specific and prostate cancer-associated noncoding gene, PCGEM1. DNA Cell Biol 2006; 25: 135–141.

    Article  PubMed  Google Scholar 

  14. Srikantan V, Zou Z, Petrovics G, Xu L, Augustus M, Davis L et al. PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer. Proc Natl Acad Sci USA 2000; 97: 12216–12221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Jin G, Sun J, Isaacs SD, Wiley KE, Kim ST, Chu LW et al. Human polymorphisms at long non-coding RNAs (lncRNAs) and association with prostate cancer risk. Carcinogenesis 2011; 32: 1655–1659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chen J, Wu Y, Shao P, Cao Q, Qin C, Li P et al. Association between VHL single nucleotide polymorphism (rs779805) and the susceptibility to prostate cancer in Chinese. DNA Cell Biol 2011; 31: 790–796.

    Article  PubMed  Google Scholar 

  17. Wang M, Liu F, Hsing AW, Wang X, Shao Q, Qi J et al. Replication and cumulative effects of GWAS-identified genetic variations for prostate cancer in Asians: a case-control study in the ChinaPCa consortium. Carcinogenesis 2012; 33: 356–360.

    Article  PubMed  Google Scholar 

  18. Heidenreich A, Aus G, Bolla M, Joniau S, Matveev VB, Schmid HP et al. EAU guidelines on prostate cancer. Eur Urol 2008; 53: 68–80.

    Article  PubMed  Google Scholar 

  19. Rohrmann S, Linseisen J, Allen N, Bueno-de-Mesquita HB, Johnsen NF, Tjonneland A et al. Smoking and the risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition. Br J Cancer 2012; 108: 708–714.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Zuccolo L, Lewis SJ, Donovan JL, Hamdy FC, Neal DE, Smith GD . Alcohol consumption and PSA-detected prostate cancer risk-A case-control nested in the ProtecT study. Int J Cancer 2012; 132: 2176–2185.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Barrett JC, Fry B, Maller J, Daly MJ . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21: 263–265.

    Article  CAS  PubMed  Google Scholar 

  22. Bialkowska-Hobrzanska H, Driman DK, Fletcher R, Harry V, Razvi H . Expression of human telomerase reverse transcriptase, Survivin, DD3 and PCGEM1 messenger RNA in archival prostate carcinoma tissue. Can J Urol 2006; 13: 2967–2974.

    PubMed  Google Scholar 

  23. Verhaegh GW, Verkleij L, Vermeulen SH, den Heijer M, Witjes JA, Kiemeney LA . Polymorphisms in the H19 gene and the risk of bladder cancer. Eur Urol 2008; 54: 1118–1126.

    Article  CAS  PubMed  Google Scholar 

  24. Liu Y, Pan S, Liu L, Zhai X, Liu J, Wen J et al. A genetic variant in long non-coding RNA HULC contributes to risk of HBV-related hepatocellular carcinoma in a Chinese population. PLoS ONE 2012; 7: e35145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ishii N, Ozaki K, Sato H, Mizuno H, Saito S, Takahashi A et al. Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction. J Hum Genet 2006; 51: 1087–1099.

    Article  CAS  PubMed  Google Scholar 

  26. Schulz WA, Burchardt M, Cronauer MV . Molecular biology of prostate cancer. Mol Hum Reprod 2003; 9: 437–448.

    Article  CAS  PubMed  Google Scholar 

  27. Amanatullah DF, Reutens AT, Zafonte BT, Fu M, Mani S, Pestell RG . Cell-cycle dysregulation and the molecular mechanisms of prostate cancer. Front Biosci 2000; 5: D372–D390.

    Article  CAS  PubMed  Google Scholar 

  28. Chin L, Artandi SE, Shen Q, Tam A, Lee SL, Gottlieb GJ et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 1999; 97: 527–538.

    Article  CAS  PubMed  Google Scholar 

  29. Young CY, Montgomery BT, Andrews PE, Qui SD, Bilhartz DL, Tindall DJ . Hormonal regulation of prostate-specific antigen messenger RNA in human prostatic adenocarcinoma cell line LNCaP. Cancer Res 1991; 51: 3748–3752.

    CAS  PubMed  Google Scholar 

  30. Huang CL, Yang CH, Yeh KH, Hu FC, Chen KY, Shih JY et al. EGFR intron 1 dinucleotide repeat polymorphism is associated with the occurrence of skin rash with gefitinib treatment. Lung Cancer 2009; 64: 346–351.

    Article  PubMed  Google Scholar 

  31. Wu D, Tian Y, Gong W, Zhu H, Zhang Z, Wang M et al. Genetic variants in the Runt-related transcription factor 3 gene contribute to gastric cancer risk in a Chinese population. Cancer Sci 2009; 100: 1688–1694.

    Article  CAS  PubMed  Google Scholar 

  32. Nasiri M, Saadat I, Omidvari S, Saadat M . Genetic variation in DNA repair gene XRCC7 (G6721T) and susceptibility to breast cancer. Gene 2012; 505: 195–197.

    Article  CAS  PubMed  Google Scholar 

  33. Ban Y, Tozaki T, Taniyama M, Skrabanek L, Nakano Y, Ban Y et al. Multiple SNPs in intron 41 of thyroglobulin gene are associated with autoimmune thyroid disease in the Japanese population. PLoS ONE 2012; 7: e37501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kereszturi E, Kiraly O, Sahin-Toth M . Minigene analysis of intronic variants in common SPINK1 haplotypes associated with chronic pancreatitis. Gut 2009; 58: 545–549.

    Article  CAS  PubMed  Google Scholar 

  35. Choi JW, Park CS, Hwang M, Nam HY, Chang HS, Park SG et al. A common intronic variant of CXCR3 is functionally associated with gene expression levels and the polymorphic immune cell responses to stimuli. J Allergy Clin Immunol 2008; 122: 1119–1126 e1117.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was partly supported by the National Natural Science Foundation of China (81230068, 30972444 and 81102089), the Key Program of Natural Science Foundation of Jiangsu Province (BK2010080), Natural Science Foundation of Jiangsu Province (BK2011773 and BK2012842), the Program for Basic Research of Jiangsu Provincial Department of Education (11KJB330002 and 12KJA330002), the Qing-Lan Project of Jiangsu Provincial Department of Education and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Z Zhang or D Wu.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Prostate Cancer and Prostatic Diseases website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xue, Y., Wang, M., Kang, M. et al. Association between lncrna PCGEM1 polymorphisms and prostate cancer risk. Prostate Cancer Prostatic Dis 16, 139–144 (2013). https://doi.org/10.1038/pcan.2013.6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/pcan.2013.6

Keywords

This article is cited by

Search

Quick links