Skip to main content

Advertisement

Log in

Polymorphisms of Caspase 8 and Caspase 9 gene and colorectal cancer susceptibility and prognosis

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

Caspase-8 (CASP8) and caspase-9 (CASP9) play crucial roles in regulating apoptosis, and their functional polymorphisms may alter cancer risk. Our aim was to investigate the association between CASP8 and CASP9 gene polymorphisms and colorectal cancer (CRC) susceptibility.

Methods

A case–control study at 402 CRC patients and 480 healthy controls was undertaken in order to investigate the association between the genotype and allelic frequencies of CASP8 −652 6N ins/del and CASP9 −1263 A>G polymorphisms and the CRC susceptibility. The polymerase chain reaction (PCR) restriction fragment length polymorphism method was used and the incidence of polymorphisms on messenger RNA (mRNA) expression levels was detected by quantitative reverse-transcriptase PCR in CRC tissues.

Results

No statistical significant association was observed between CASP8 −652 6N ins/del polymorphism frequencies and CRC susceptibility. CASP9 −1263 G allele was observed to be significant associated with reduced risk of CRC. Homozygotes for the −1263 GG CASP9 genotype, and hetrozygotes for the −1263 AG genotype expressed 6.64- and 3.69-fold higher mRNA levels of Caspase-9, respectively compared to the −1263 AA genotype cases. No significant association was observed between CASP9 −1263 A>G polymorphism and tumor characteristics. The CASP9 −1263 GG genotype was associated with increased overall survival in CRC patients.

Conclusion

The CASP9 −1263 A>G polymorphism was observed to play a protective role in CRC predisposition, while the CASP9 −1263 GG genotype may confer a better prognosis at CRC patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Savas S, Younghusband HB (2010) dbCPCO: a database of genetic markers tested for their predictive and prognostic value in colorectal cancer. Hum Mutat 31:901–907

    Article  PubMed  CAS  Google Scholar 

  2. Kinzler KW, Vogelstein B (1996) Lessons from hereditary colorectal carcinoma. Cell 87:159–170

    Article  PubMed  CAS  Google Scholar 

  3. Wang W, Spitz MR, Yang H, Lu C, Stewart DJ, Wu X (2007) Genetic variants in cell cycle control pathway confer susceptibility to lung cancer. Clin Cancer Res 13:5974–5981

    Article  PubMed  CAS  Google Scholar 

  4. Ye Y, Yang H, Grossman HB, Dinney C, Wu X, Gu J (2008) Genetic variants in cell cycle control pathway confer susceptibility to bladder cancer. Cancer 112:2467–2474

    Article  PubMed  CAS  Google Scholar 

  5. Hajra KM, Liu JR (2004) Apoptosome dysfunction in human cancer. Apoptosis 9:691–704

    Article  PubMed  CAS  Google Scholar 

  6. Nicholson DW, Thornberry NA (1997) Caspases: killer proteases. Trends Biochem Sci 22:299–306

    Article  PubMed  CAS  Google Scholar 

  7. Cox A, Dunning AM, Garcia-Closas M et al (2007) A common coding variant in CASP8 is associated with breast cancer risk. Nat Genet 39:352–358

    Article  PubMed  CAS  Google Scholar 

  8. Sun T, Gao Y, Tan W et al (2007) A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancers. Nat Genet 39:605–613

    Article  PubMed  CAS  Google Scholar 

  9. Haiman CA, Garcia RR, Kolonel LN, Henderson BE, Wu AH, Le Marchand L (2008) A promoter polymorphism in the CASP8 gene is not associated with cancer risk. Nat Genet 40:259–260

    Article  PubMed  CAS  Google Scholar 

  10. Gangwar R, Mandhani A, Mittal RD (2009) Caspase 9 and caspase 8 gene polymorphisms and susceptibility to bladder cancer in north Indian population. Ann Surg Oncol 16:2028–2034

    Article  PubMed  Google Scholar 

  11. Shivapurkar N, Reddy J, Chaudhary PM, Gazdar AF (2003) Apoptosis and lung cancer: a review. J Cell Biochem 88:885–898

    Article  PubMed  CAS  Google Scholar 

  12. Theodoropoulos GE, Michalopoulos NV, Panoussopoulos SG, Taka S, Gazouli M (2010) Effects of caspase-9 and survivin gene polymorphisms in pancreatic cancer risk and tumor characteristics. Pancreas 39:976–980

    Article  PubMed  CAS  Google Scholar 

  13. Morson BC, Sobin LH (1976) Histologic typing of intestinal tumours: WHO technical report. WHO, Geneva

    Google Scholar 

  14. Sobin LH, Wittekind C (1997) UICC TNM classification of malignant tumours, 5th edn. Wiley, New York

    Google Scholar 

  15. Pittman AH, Broderick P, Sullivan K et al (2008) CASP8 variants D302H and −652 6N ins/del do not influence the risk of colorectal cancer in the United Kingdom population. Br J Cancer 98:1434–1436

    Article  PubMed  CAS  Google Scholar 

  16. Liu B, ZhangY JM et al (2010) Association of selected polymorphisms of CCND1, p21, and caspase8 with colorectal cancer risk. Mol Carcinog 49:75–84

    Article  PubMed  CAS  Google Scholar 

  17. Twiddy D, Cain K. (2007) Caspase-9 cleavage, do you need it? J Biochem 405.

  18. Park JY, Park JM, Jang JS et al (2006) Caspase 9 promoter polymorphisms and risk of primary lung cancer. Hum Mol Genet 1:1963–1971

    Article  Google Scholar 

  19. Chua W, Goldstein D, Lee CK et al (2009) Molecular markers of response and toxicity to FOLFOX chemotherapy in metastatic colorectal cancer. Br J Cancer 101:998–1004

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The study was supported by National Resources “KAPODISTRIAS” 70/4/9923 to GE Theodoropoulos.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to George E. Theodoropoulos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Theodoropoulos, G.E., Gazouli, M., Vaiopoulou, A. et al. Polymorphisms of Caspase 8 and Caspase 9 gene and colorectal cancer susceptibility and prognosis. Int J Colorectal Dis 26, 1113–1118 (2011). https://doi.org/10.1007/s00384-011-1217-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-011-1217-5

Keywords

Navigation