Skip to main content

Genetic polymorphism in ornithine decarboxylase and risk of breast cancer

Familial Cancer volume 8, pages 307–311 (2009)Cite this article

Abstract

Ornithine decarboxylase (ODC), the first enzyme in the biosynthesis of polyamines, has increased activity in breast cancer tissue compared with benign and normal tissues. The ODC gene contains a single nucleotide polymorphism in which a guanine is substituted for an adenine. This study investigated whether the ODC +316 G > A polymorphism (rs2302615) was associated with the risk of developing breast cancer. A case–control study involving 121 controls, without breast cancer, 46 patients with breast cancer but without a family history, and 130 breast cancer cases with a family history of breast cancer was conducted. A nested PCR-restriction fragment length polymorphism procedure and the TaqMan 5′ nuclease assay was used to genotype individuals. Risk was significantly lower for heterozygote (GA genotype) individuals [odds ratio (OR) = 0.39, 95% confidence interval (CI) 0.17–0.86, P = 0.018], or individuals with at least one A allele (OR = 0.44, 95% CI 0.21–0.92, P = 0.027), without family history. This protective effect of having at least one copy of the variant A allele was not as strong, however, in those with a family history of the disease. In sporadic breast cancer, the presence of at least one A allele is protective against the disease. The influence of this polymorphism may be less important in individuals with an inherited breast cancer predisposition.

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

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Wallace HM, Fraser AV, Hughes A (2003) A perspective of polyamine metabolism. Biochem J 376:1–14. doi:10.1042/BJ20031327

    Article  CAS  PubMed  Google Scholar 

  2. Fair WR, Wehner N, Brorsson U (1975) Urinary polyamine levels in the diagnosis of carcinoma of the prostate. J Urol 114:88–92

    CAS  PubMed  Google Scholar 

  3. Kingsnorth AN, Wallace HM, Bundred NJ, Dixon JM (1984) Polyamines in breast cancer. Br J Surg 71:352–356. doi:10.1002/bjs.1800710513

    Article  CAS  PubMed  Google Scholar 

  4. Kingsnorth AN, Lumsden AB, Wallace HM (1984) Polyamines in colorectal cancer. Br J Surg 71:791–794. doi:10.1002/bjs.1800711019

    Article  CAS  PubMed  Google Scholar 

  5. Loser C, Folsch UR, Paprotny C, Creutzfeldt W (1990) Polyamine concentrations in pancreatic tissue, serum, and urine of patients with pancreatic cancer. Pancreas 5:119–127

    CAS  PubMed  Google Scholar 

  6. Tabib A, Bachrach U (1998) Polyamines induce malignant transformation in cultured NIH 3T3 fibroblasts. Int J Biochem Cell Biol 30:135–146. doi:10.1016/S1357-2725(97)00073-3

    Article  CAS  PubMed  Google Scholar 

  7. Takigawa M, Enomoto M, Nishida Y et al (1990) Tumor angiogenesis and polyamines: alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, inhibits B16 melanoma-induced angiogenesis in ovo and the proliferation of vascular endothelial cells in vitro. Cancer Res 50:4131–4138

    CAS  PubMed  Google Scholar 

  8. Jasnis MA, Klein S, Monte M et al (1994) Polyamines prevent DFMO-mediated inhibition of angiogenesis. Cancer Lett 79:39–43. doi:10.1016/0304-3835(94)90060-4

    Article  CAS  PubMed  Google Scholar 

  9. Canizares F, Salinas J, de las Heras M et al (1999) Prognostic value of ornithine decarboxylase and polyamines in human breast cancer: correlation with clinicopathologic parameters. Clin Cancer Res 5:2035–2041

    CAS  PubMed  Google Scholar 

  10. Kingsnorth AN, Wallace HM (1985) Elevation of monoacetylated polyamines in human breast cancers. Eur J Cancer Clin Oncol 21:1057–1062. doi:10.1016/0277-5379(85)90291-3

    Article  CAS  PubMed  Google Scholar 

  11. Manni A, Washington S, Griffith JW et al (2002) Influence of polyamines on in vitro and in vivo features of aggressive and metastatic behavior by human breast cancer cells. Clin Exp Metastasis 19:95–105. doi:10.1023/A:1014536909007

    Article  CAS  PubMed  Google Scholar 

  12. Kubota S, Yamada T, Kamei S, Seyama Y (1995) Ornithine decarboxylase is directly involved in mouse mammary carcinoma cell invasion in vitro. Biochem Biophys Res Commun 208:1106–1115. doi:10.1006/bbrc.1995.1448

    Article  CAS  PubMed  Google Scholar 

  13. Manni A, Mauger D, Gimotty P, Badger B (1996) Prognostic influence on survival of increased ornithine decarboxylase activity in human breast cancer. Clin Cancer Res 2:1901–1906

    CAS  PubMed  Google Scholar 

  14. Manni A, Grove R, Kunselman S, Aldaz M (1995) Involvement of the polyamine pathway in breast cancer progression. Cancer Lett 92:49–57. doi:10.1016/0304-3835(95)03763-M

    Article  CAS  PubMed  Google Scholar 

  15. Radford DM, Nakai H, Eddy RL et al (1990) Two chromosomal locations for human ornithine decarboxylase gene sequences and elevated expression in colorectal neoplasia. Cancer Res 50:6146–6153

    CAS  PubMed  Google Scholar 

  16. Guo Y, Harris RB, Rosson D et al (2000) Functional analysis of human ornithine decarboxylase alleles. Cancer Res 60:6314–6317

    CAS  PubMed  Google Scholar 

  17. Sharp L, Little J, Schofield AC et al (2002) Folate and breast cancer: the role of polymorphisms in methylenetetrahydrofolate reductase (MTHFR). Cancer Lett 181:65–71. doi:10.1016/S0304-3835(02)00030-7

    Article  CAS  PubMed  Google Scholar 

  18. Visvanathan K, Helzlsouer KJ, Boorman DW et al (2004) Association among an ornithine decarboxylase polymorphism, androgen receptor gene (CAG) repeat length and prostate cancer risk. J Urol 171:652–655. doi:10.1097/01.ju.0000108384.74718.73

    Article  PubMed  Google Scholar 

  19. Martinez ME, O’Brien TG, Fultz KE et al (2003) Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene. Proc Natl Acad Sci USA 100:7859–7864. doi:10.1073/pnas.1332465100

    Article  CAS  PubMed  Google Scholar 

  20. Barry ELR, Baron JA, Bhat S et al (2006) Ornithine decarboxylase modification of response to aspirin treatment for colorectal adenoma prevention. J Natl Cancer Inst 98:1494–1500. doi:10.1571/cs4-6-06cc

    CAS  PubMed  Article  Google Scholar 

  21. Pegg AE (2006) Regulation of ornithine decarboxylase. J Biol Chem 281:14529–14532. doi:10.1074/jbc.R500031200

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Professor Thomas O’Brien for providing us with positive control DNA for the polymorphic alleles and also the Department of Medical Genetics, NHS Grampian, for providing DNA samples from breast cancer patients with a known family history of the disease. We also thank Dr Linda Sharp and Jonathan Baird for collecting and extracting DNA from mouthwash samples. We are grateful to NHS Grampian Endowments for financial assistance.

Author information

Affiliations

  1. School of Medicine & Dentistry, College of Life Sciences and Medicine, University of Aberdeen, Medical School, Foresterhill, Aberdeen, AB25 2ZD, UK

    Iain Brown, Susan Halliday, Heather Greig, Steven D. Heys, Heather M. Wallace & Andrew C. Schofield

Authors
  1. Iain Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan Halliday
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heather Greig
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steven D. Heys
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Heather M. Wallace
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrew C. Schofield
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Iain Brown.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Brown, I., Halliday, S., Greig, H. et al. Genetic polymorphism in ornithine decarboxylase and risk of breast cancer. Familial Cancer 8, 307–311 (2009). https://doi.org/10.1007/s10689-009-9237-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-009-9237-9

Keywords

  • Breast cancer
  • Case–control study
  • ODC
  • Polyamine
  • Gene polymorphism