Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
2014-January Volume 31 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
2014-January Volume 31 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Association between single nucleotide polymorphisms in the p53 pathway and response to radiotherapy in patients with nasopharyngeal carcinoma

  • Authors:
    • Xiaoxue Xie
    • Hekun Jin
    • Jun Hu
    • Yong Zeng
    • Jumei Zhou
    • Shuyu Ouyang
    • Wenjuan Yang
    • Bingqiang Hu
    • Hui Wang
  • View Affiliations / Copyright

    Affiliations: Department of Radiation Oncology, Hunan Provincial Tumor Hospital and Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, P.R. China, Department of Pathology, Hunan Provincial Tumor Hospital and Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, P.R. China, Department of Clinical Pharmacology Research Base, Hunan Provincial Tumor Hospital and Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013, P.R. China
  • Pages: 223-231
    |
    Published online on: October 24, 2013
       https://doi.org/10.3892/or.2013.2808
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Single nucleotide polymorphisms (SNPs) in the p53, MDM2 and p21 genes of the p53 pathway have been extensively studied. The main aim of the current retrospective study was to evaluate the possible predictive value of SNPs in the p53 pathway in locoregionally advanced nasopharyngeal carcinoma (NPC) in response to radiotherapy. In total, 75 consecutive patients with locoregionally advanced NPC were enrolled. Three SNPs in the p53 pathway were identified using the Sanger sequencing method from retrospectively collected paraffin-embedded biopsy specimens. The effects of genetic polymorphisms on patient progression‑free survival (PFS) were analyzed using the Cox proportional hazards model, Kaplan-Meier method and log-rank test. All of the selected subjects completed questionnaires on smoking habits prior to treatment. Multivariate analysis showed that the p53 codon 72 Pro/Pro genotype [hazard ratio (HR), 0.300; 95% confidence interval (CI), 0.092-0.983; P=0.047] and heavy smoking (≥30 pack-years) (HR, 2.899; 95% CI, 1.349-6.229; P=0.006) are independent significant prognostic factors for PFS in patients with locoregionally advanced NPC. Moreover, mean times to disease progression for heavy smokers (≥20 pack-years) carrying p53 codon 72 Arg/Arg, p21 codon 31 Arg/Arg and MDM2 309 SNP G/G genotypes were only 14.78±3.00, 11.00±0.58 and 11.17±1.85 months, respectively. These time scales were less than half of those recorded for patients containing other genotypes and moderate smokers (<20 pack-years). In conclusion, the p53 codon 72 polymorphism is an independent prognostic marker for locoregionally advanced NPC. Moreover, analysis of SNPs in the p53 pathway may facilitate the identification of patients at high risk of poor disease outcome in subgroups of heavy smokers.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Buchman VL, Chumakov PM, Ninkina NN, Samarina OP and Georgiev GP: A variation in the structure of the protein-coding region of the human p53 gene. Gene. 70:245–252. 1988. View Article : Google Scholar : PubMed/NCBI

2 

Thomas M, Kalita A, Labrecque S, Pim D, Banks L and Matlashewski G: Two polymorphic variants of wild-type p53 differ biochemically and biologically. Mol Cell Biol. 19:1092–1100. 1999.PubMed/NCBI

3 

Dumont P, Leu JI, Della Pietra AC III, George DL and Murphy M: The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet. 33:357–365. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Sullivan A, Syed N, Gasco M, Bergamaschi D, Trigiante G, Attard M, et al: Polymorphism in wild-type p53 modulates response to chemotherapy in vitro and in vivo. Oncogene. 23:3328–3337. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Pim D and Banks L: p53 polymorphic variants at codon 72 exert different effects on cell cycle progression. Int J Cancer. 108:196–199. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Bergamaschi D, Samuels Y, Sullivan A, Zvelebil M, Breyssens H, Bisso A, et al: iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53. Nat Genet. 38:1133–1141. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Vannini I, Zoli W, Tesei A, Rosetti M, Sansone P, Storci G, et al: Role of p53 codon 72 arginine allele in cell survival in vitro and in the clinical outcome of patients with advanced breast cancer. Tumor Biol. 29:145–151. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Kim JG, Sohn SK, Chae YS, Song HS, Kwon KY, Do YR, et al: TP53 codon 72 polymorphism associated with prognosis in patients with advanced gastric cancer treated with paclitaxel and cisplatin. Cancer Chemother Pharmacol. 64:355–360. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Bergamaschi D, Gasco M, Hiller L, Sullivan A, Syed N, Trigiante G, et al: p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis. Cancer Cell. 3:387–402. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Lo KW and Huang DP: Genetic and epigenetic changes in nasopharyngeal carcinoma. Semin Cancer Biol. 12:451–462. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Zhuo XL, Cai L, Xiang ZL, Zhuo WL, Wang Y and Zhang XY: TP53 codon 72 polymorphism contributes to nasopharyngeal cancer susceptibility: a meta-analysis. Arch Med Res. 40:299–305. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC, et al: A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell. 119:591–602. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Bond GL and Levine AJ: A single nucleotide polymorphism in the p53 pathway interacts with gender, environmental stresses and tumor genetics to influence cancer in humans. Oncogene. 26:1317–1323. 2007. View Article : Google Scholar

14 

Hu Z, Jin G, Wang L, Chen F, Wang X and Shen H: MDM2 promoter polymorphism SNP309 contributes to tumor susceptibility: evidence from 21 case-control studies. Cancer Epidemiol Biomarkers Prev. 16:2717–2723. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Tu HF, Chen HW, Kao SY, Lin SC, Liu CJ and Chang KW: MDM2 SNP 309 and p53 codon 72 polymorphisms are associated with the outcome of oral carcinoma patients receiving postoperative irradiation. Radiother Oncol. 87:243–252. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Chaar I, Arfaoui TA, El Amine el HO, Mahmoud LB, Khiari M, Sammoud S, et al: Impact of MDM2 polymorphism: increased risk of developing colorectal cancer and a poor prognosis in the Tunisian population. Eur J Gastroenterol Hepatol. 24:320–327. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Zawlik I, Kita D, Vaccarella S, Mittelbronn M, Franceschi S and Ohgaki H: Common polymorphisms in the MDM2 and TP53 genes and the relationship between TP53 mutations and patient outcomes in glioblastomas. Brain Pathol. 19:188–194. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Zhou G, Zhai Y, Cui Y, Zhang X, Dong X, Yang H, et al: MDM2 promoter SNP309 is associated with risk of occurrence and advanced lymph node metastasis of nasopharyngeal carcinoma in Chinese population. Clin Cancer Res. 13:2627–2633. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Sousa H, Pando M, Breda E, Catarino R and Medeiros R: Role of the MDM2 SNP309 polymorphism in the initiation and early age of onset of nasopharyngeal carcinoma. Mol Carcinog. 50:73–79. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Brugarolas J, Chandrasekaran C, Gordon JI, Beach D, Jacks T and Hannon GJ: Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature. 377:552–557. 1995. View Article : Google Scholar : PubMed/NCBI

21 

Deng C, Zhang P, Harper JW, Elledge SJ and Leder P: Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell. 82:675–684. 1995.

22 

Macleod KF, Sherry N, Hannon G, Beach D, Tokino T, Kinzler K, et al: p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. Genes Dev. 9:935–944. 1995. View Article : Google Scholar : PubMed/NCBI

23 

Abbas T and Dutta A: p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer. 9:400–414. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Birgander R, Själander A, Saha N, Spitsyn V, Beckman L and Beckman G: The codon 31 polymorphism of the p53-inducible gene p21 shows distinct differences between major ethnic groups. Hum Hered. 46:148–154. 1996. View Article : Google Scholar : PubMed/NCBI

25 

Su L, Sai Y, Fan R, Thurston SW, Miller DP, Zhou W, et al: P53 (codon 72) and P21 (codon 31) polymorphisms alter in vivo mRNA expression of p21. Lung Cancer. 40:259–266. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Johnson GG, Sherrington PD, Carter A, Lin K, Liloglou T, Field JK and Pettitt AR: A novel type of p53 pathway dysfunction in chronic lymphocytic leukemia resulting from two interacting single nucleotide polymorphisms within the p21 gene. Cancer Res. 69:5210–5217. 2009. View Article : Google Scholar

27 

Tan XL, Popanda O, Ambrosone CB, Kropp S, Helmbold I, von Fournier D, et al: Association between TP53 and p21 genetic polymorphisms and acute side effects of radiotherapy in breast cancer patients. Breast Cancer Res Treat. 97:255–262. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Tsai MH, Chen WC and Tsai FJ: Correlation of p21 gene codon 31 polymorphism and TNF-alpha gene polymorphism with nasopharyngeal carcinoma. J Clin Lab Anal. 16:146–150. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Marin MC, Jost CA, Brooks LA, Irwin MS, O’Nions J, Tidy JA, et al: A common polymorphism acts as an intragenic modifier of mutant p53 behaviour. Nat Genet. 25:47–54. 2000. View Article : Google Scholar : PubMed/NCBI

30 

Alhopuro P, Ylisaukko-Oja SK, Koskinen WJ, Bono P, Arola J, Järvinen HJ, et al: The MDM2 promoter polymorphism SNP309T→G and the risk of uterine leiomyosarcoma, colorectal cancer, and squamous cell carcinoma of the head and neck. J Med Genet. 42:694–698. 2005.

31 

Giordana MT, Duo D, Gasverde S, Trevisan E, Boghi A, Morra I, et al: MDM2 overexpression is associated with short survival in adults with medulloblastoma. Neuro Oncol. 4:115–122. 2002.PubMed/NCBI

32 

Haitel A, Wiener HG, Baethge U, Marberger M and Susani M: Mdm2 expression as a prognostic indicator in clear cell renal cell carcinoma: comparison with p53 overexpression and clinic pathological parameters. Clin Cancer Res. 6:1840–1844. 2000.PubMed/NCBI

33 

Polsky D, Melzer K, Hazan C, Panageas KS, Busam K, Drobnjak M, et al: HDM2 protein overexpression and prognosis in primary malignant melanoma. J Natl Cancer Inst. 94:1803–1806. 2002. View Article : Google Scholar : PubMed/NCBI

34 

Ranuncolo SM, Varela M, Morandi A, Lastiri J, Christiansen S, Bal de Kier Joffé E, et al: Prognostic value of Mdm2, p53 and p16 in patients with astrocytomas. J Neurooncol. 68:113–121. 2004. View Article : Google Scholar : PubMed/NCBI

35 

Hoff CM, Grau C and Overgaard J: Effect of smoking on oxygen delivery and outcome in patients treated with radiotherapy for head and neck squamous cell carcinoma - a prospective study. Radiother Oncol. 103:38–44. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xie X, Jin H, Hu J, Zeng Y, Zhou J, Ouyang S, Yang W, Hu B and Wang H: Association between single nucleotide polymorphisms in the p53 pathway and response to radiotherapy in patients with nasopharyngeal carcinoma. Oncol Rep 31: 223-231, 2014.
APA
Xie, X., Jin, H., Hu, J., Zeng, Y., Zhou, J., Ouyang, S. ... Wang, H. (2014). Association between single nucleotide polymorphisms in the p53 pathway and response to radiotherapy in patients with nasopharyngeal carcinoma. Oncology Reports, 31, 223-231. https://doi.org/10.3892/or.2013.2808
MLA
Xie, X., Jin, H., Hu, J., Zeng, Y., Zhou, J., Ouyang, S., Yang, W., Hu, B., Wang, H."Association between single nucleotide polymorphisms in the p53 pathway and response to radiotherapy in patients with nasopharyngeal carcinoma". Oncology Reports 31.1 (2014): 223-231.
Chicago
Xie, X., Jin, H., Hu, J., Zeng, Y., Zhou, J., Ouyang, S., Yang, W., Hu, B., Wang, H."Association between single nucleotide polymorphisms in the p53 pathway and response to radiotherapy in patients with nasopharyngeal carcinoma". Oncology Reports 31, no. 1 (2014): 223-231. https://doi.org/10.3892/or.2013.2808
Copy and paste a formatted citation
x
Spandidos Publications style
Xie X, Jin H, Hu J, Zeng Y, Zhou J, Ouyang S, Yang W, Hu B and Wang H: Association between single nucleotide polymorphisms in the p53 pathway and response to radiotherapy in patients with nasopharyngeal carcinoma. Oncol Rep 31: 223-231, 2014.
APA
Xie, X., Jin, H., Hu, J., Zeng, Y., Zhou, J., Ouyang, S. ... Wang, H. (2014). Association between single nucleotide polymorphisms in the p53 pathway and response to radiotherapy in patients with nasopharyngeal carcinoma. Oncology Reports, 31, 223-231. https://doi.org/10.3892/or.2013.2808
MLA
Xie, X., Jin, H., Hu, J., Zeng, Y., Zhou, J., Ouyang, S., Yang, W., Hu, B., Wang, H."Association between single nucleotide polymorphisms in the p53 pathway and response to radiotherapy in patients with nasopharyngeal carcinoma". Oncology Reports 31.1 (2014): 223-231.
Chicago
Xie, X., Jin, H., Hu, J., Zeng, Y., Zhou, J., Ouyang, S., Yang, W., Hu, B., Wang, H."Association between single nucleotide polymorphisms in the p53 pathway and response to radiotherapy in patients with nasopharyngeal carcinoma". Oncology Reports 31, no. 1 (2014): 223-231. https://doi.org/10.3892/or.2013.2808
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team