Skip to main content
SpringerLink
Log in

Common Variants in IGF1 Pathway Genes and Clinical Outcomes After Radical Prostatectomy

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Insulin-like growth factor-1 (IGF1) pathway plays a critical role in malignant transformation, and epidemiology studies have also shown that single nucleotide polymorphisms (SNPs) in IGF1 pathway genes are associated with prostate cancer risk. However, the clinical significance of these SNPs on prostate cancer aggressiveness and prognosis after radical prostatectomy (RP) has not been determined.

Methods

We evaluated the associations of 4 common SNPs in IGF1 and IGF1R with age at diagnosis, preoperative prostate-specific antigen (PSA) level, pathologic Gleason score, pathologic stage, surgical margin, lymph node metastasis, and PSA recurrence in a cohort of 320 localized prostate cancer patients receiving RP. The prognostic significance on time to PSA recurrence was also assessed by Cox proportional hazards model.

Results

IGF1 rs2946834 alleles/genotypes and an IGF1 specific haplotype AT, containing the minor allele of rs2946834, were associated (P ≤ 0.028) with a 1.49- to 2.22-fold higher risk of having advanced-stage prostate cancer. In addition, a genetic interaction profile consisting of IGF1 rs2946834 and IGF1R rs2016347 was significantly associated with PSA recurrence (P = 0.033).

Conclusions

Our study is the first to evaluate the impact of SNPs in IGF1 pathway genes on PSA recurrence. A genetic interaction between IGF1 rs2946834 and IGF1R rs2016347 might be a predictor of outcomes following RP.

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

Access this article

Log in via an institution

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. Pollak MN, Schernhammer ES, Hankinson SE. Insulin-like growth factors and neoplasia. Nat Rev Cancer. 2004;4:505–18.

    Article  PubMed  CAS  Google Scholar 

  2. Sell C, Rubini M, Rubin R, Liu JP, Efstratiadis A, Baserga. Simian virus 40 large tumor antigen is unable to transform mouse embryonic fibroblasts lacking type 1 insulin-like growth factor receptor. Proc Natl Acad Sci USA. 1993;90:11217–21.

    Article  PubMed  CAS  Google Scholar 

  3. Key TJ, Appleby PN, Reeves GK, Roddam AW. Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol. 2010;11:530–42.

    Article  PubMed  Google Scholar 

  4. Ma J, Pollak MN, Giovannucci E, Chan JM, Tao Y, Hennekens CH, et al. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst. 1999;91:620–5.

    Article  PubMed  CAS  Google Scholar 

  5. Roddam AW, Allen NE, Appleby P, Key TJ, Ferrucci L, Carter HB, et al. Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies. Ann Intern Med. 2008;149:461–71, W83–8.

    Article  PubMed  Google Scholar 

  6. Hall K, Hilding A, Thoren M. Determinants of circulating insulin-like growth factor-I. J Endocrinol Invest. 1999;22:48–57.

    PubMed  CAS  Google Scholar 

  7. Gu F, Schumacher FR, Canzian F, Allen NE, Albanes D, Berg CD, et al. Eighteen insulin-like growth factor pathway genes, circulating levels of IGF-I and its binding protein, and risk of prostate and breast cancer. Cancer Epidemiol Biomarkers Prev. 2010;19:2877–87.

    Article  PubMed  CAS  Google Scholar 

  8. Schumacher FR, Cheng I, Freedman ML, Mucci L, Allen NE, Pollak MN, et al. A comprehensive analysis of common IGF1, IGFBP1 and IGFBP3 genetic variation with prospective IGF-I and IGFBP-3 blood levels and prostate cancer risk among Caucasians. Hum Mol Genet. 2010;19:3089–101.

    Article  PubMed  CAS  Google Scholar 

  9. Bao BY, Lin VC, Huang SH, Pao JB, Chang TY, Lu TL, et al. Clinical significance of tumor necrosis factor receptor superfamily member 11b polymorphism in prostate cancer. Ann Surg Oncol. 2010;17:1675–81.

    Article  PubMed  Google Scholar 

  10. Bao BY, Pao JB, Lin VC, Huang CN, Chang TY, Lan YH, et al. Individual and cumulative association of prostate cancer susceptibility variants with clinicopathologic characteristics of the disease. Clin Chim Acta. 2010;411:1232–7.

    Article  PubMed  CAS  Google Scholar 

  11. Huang SP, Huang LC, Ting WC, Chen LM, Chang TY, Lu TL, et al. Prognostic significance of prostate cancer susceptibility variants on prostate-specific antigen recurrence after radical prostatectomy. Cancer Epidemiol Biomarkers Prev. 2009;18:3068–74.

    Article  PubMed  CAS  Google Scholar 

  12. Huang SP, Ting WC, Chen LM, Huang LC, Liu CC, Chen CW, et al. Association analysis of Wnt pathway genes on prostate-specific antigen recurrence after radical prostatectomy. Ann Surg Oncol. 2010;17:312–22.

    Article  PubMed  Google Scholar 

  13. Freedland SJ, Sutter ME, Dorey F, Aronson WJ. Defining the ideal cutpoint for determining PSA recurrence after radical prostatectomy. Prostate-specific antigen. Urology. 2003;61:365–9.

    Article  PubMed  Google Scholar 

  14. Al-Zahrani A, Sandhu MS, Luben RN, Thompson D, Baynes C, Pooley KA, et al. IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer. Hum Mol Genet. 2006;15:1–10.

    Article  PubMed  CAS  Google Scholar 

  15. Diorio C, Brisson J, Berube S, Pollak M. Genetic polymorphisms involved in insulin-like growth factor (IGF) pathway in relation to mammographic breast density and IGF levels. Cancer Epidemiol Biomarkers Prev. 2008;17:880–8.

    Article  PubMed  CAS  Google Scholar 

  16. Lonn S, Rothman N, Shapiro WR, Fine HA, Selker RG, Black PM, et al. Genetic variation in insulin-like growth factors and brain tumor risk. Neuro Oncol. 2008;10:553–9.

    Article  PubMed  CAS  Google Scholar 

  17. Verheus M, McKay JD, Kaaks R, Canzian F, Biessy C, Johansson M, et al. Common genetic variation in the IGF-1 gene, serum IGF-I levels and breast density. Breast Cancer Res Treat. 2008;112:109–22.

    Article  PubMed  CAS  Google Scholar 

  18. Hahn LW, Ritchie MD, Moore JH. Multifactor dimensionality reduction software for detecting gene–gene and gene-environment interactions. Bioinformatics. 2003;19:376–82.

    Article  PubMed  CAS  Google Scholar 

  19. Mazumder B, Seshadri V, Fox PL. Translational control by the 3′-UTR: the ends specify the means. Trends Biochem Sci. 2003;28:91–8.

    Article  PubMed  CAS  Google Scholar 

  20. Wu JD, Haugk K, Woodke L, Nelson P, Coleman I, Plymate SR. Interaction of IGF signaling and the androgen receptor in prostate cancer progression. J Cell Biochem. 2006;99:392–401.

    Article  PubMed  CAS  Google Scholar 

  21. Patel AV, Cheng I, Canzian F, Le Marchand L, Thun MJ, Berg CD, et al. IGF-1, IGFBP-1, and IGFBP-3 polymorphisms predict circulating IGF levels but not breast cancer risk: findings from the Breast and Prostate Cancer Cohort Consortium (BPC3). PLoS One. 2008;3:e2578.

    Article  PubMed  Google Scholar 

  22. Pollak M, Beamer W, Zhang JC. Insulin-like growth factors and prostate cancer. Cancer Metastasis Rev. 1998;17:383–90.

    Article  PubMed  CAS  Google Scholar 

  23. Tsuchiya N, Wang L, Suzuki H, Segawa T, Fukuda H, Narita S, et al. Impact of IGF-I and CYP19 gene polymorphisms on the survival of patients with metastatic prostate cancer. J Clin Oncol. 2006;24:1982–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by the National Science Council (NSC), Taiwan (Grants NSC-98-2320-B-039-019-MY3, NSC-99-2314-B-037-018-MY3, and NSC-100-2314-B-039-009-MY3), China Medical University (Grant CMU99-COL-13), and Kaohsiung Medical University Hospital (Grant KMUH99-9R12). We thank Chao-Shih Chen for data analysis, and the National Center for Genome Medicine, NSC, Taiwan, for technical support.

Author information

Authors and Affiliations

  1. Department of Anatomy, School of Medicine, China Medical University, Taichung, Taiwan

    Chi-Fen Chang PhD

  2. Department of Pharmacy, Yangming Branch, Taipei City Hospital, Taipei, Taiwan

    Jiunn-Bey Pao MS & Ying-Pi Yang MS

  3. Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

    Chia-Cheng Yu MD

  4. Department of Urology, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Chia-Cheng Yu MD

  5. Department of Pharmacy, Tajen University, Pingtung, Taiwan

    Chia-Cheng Yu MD

  6. Department of Urology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

    Chao-Yuan Huang MD, PhD

  7. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Shu-Pin Huang MD, PhD & Chun-Nung Huang MD, PhD

  8. Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Shu-Pin Huang MD, PhD

  9. Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Shu-Pin Huang MD, PhD & Chun-Nung Huang MD, PhD

  10. Department of Occupational Safety and Health, China Medical University, Taichung, Taiwan

    Ta-Yuan Chang PhD

  11. Department of Chinese Medicine Resources, China Medical University, Taichung, Taiwan

    Bang-Jau You PhD

  12. Department of Pharmacy, China Medical University, Taichung, Taiwan

    Hong-Zin Lee PhD & Bo-Ying Bao PhD

  13. Institute of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan

    Tzyh-Chyuan Hour PhD

  14. Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan

    Bo-Ying Bao PhD

Authors
  1. Chi-Fen Chang PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiunn-Bey Pao MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chia-Cheng Yu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chao-Yuan Huang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shu-Pin Huang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ying-Pi Yang MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chun-Nung Huang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ta-Yuan Chang PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bang-Jau You PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hong-Zin Lee PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Tzyh-Chyuan Hour PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Bo-Ying Bao PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Tzyh-Chyuan Hour PhD or Bo-Ying Bao PhD.

Additional information

C.-F. Chang and J.-B. Pao contributed equally to this study.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 111 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chang, CF., Pao, JB., Yu, CC. et al. Common Variants in IGF1 Pathway Genes and Clinical Outcomes After Radical Prostatectomy. Ann Surg Oncol 20, 2446–2452 (2013). https://doi.org/10.1245/s10434-013-2884-y

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-013-2884-y

Keywords

Search

Navigation