Skip to main content
SpringerLink
Log in

Investigation of insulin resistance gene polymorphisms in patients with differentiated thyroid cancer

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

We aimed to investigate insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), insulin-like growth factor binding protein-3 (IGFBP-3) genotypes, which are thought to be involved in the pathogenesis of many solid tumors and have thus far not been studied in patients with differentiated thyroid cancer (DTC). The study consisted of 93 patients diagnosed with DTC (79 females, 14 males) and 111 healthy control subjects (63 females, 48 males). The anthropometric measurements, lipid profiles, thyroid function tests and homeostatic model assessment (HOMA) as an indicator of insulin resistance (IR) of all patients were recorded. In addition IRS-1, IRS-2 and IGFBP-3 gene polymorphisms were determined by using polymerase chain reaction and restriction fragment length polymorphism. Hardy–Weinberg equilibrium was tested for each gene polymorphisms, and genetic effects were evaluated by the Chi Square test and multiple logistic regression. Homeostasis model assessment of insulin resistance (HOMA-IR), body mass index, waist circumference and serum total cholesterol levels were significantly higher in patients with DTC than in the control group. There was no difference between the two groups with respect to IRS-1, IRS-2 and IGFBP-3 gene polymorphisms. In addition, these gene polymorphisms were found to have no effect on lymph node metastases or tumor staging. While, obesity and increased HOMA-IR may be risk factors in DTC development, we suggest that IRS-1, IRS-2 and IGFBP-3 gene polymorphisms do not play an important role in pathogenesis of DTC.

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

Similar content being viewed by others

References

  1. Enwold L, Zhu K, Ron E, Marrogi AJ, Stojadinovic A, Peoples GE et al (2009) Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980–2005. Cancer Epidemiol Biomarkers Prev 18:784

    Article  Google Scholar 

  2. Tucker MA, Jones PH, Boice JD, Robison LL, Stone BJ, Stovall M et al (1991) Therapeutic radiation at a young age is linked to secondary thyroid cancer. The late effects study group. Cancer Res 51(11):2885–2888

    CAS  PubMed  Google Scholar 

  3. Ron E, Lubin JH, Shore RE, Mabuchi K, Modan B, Pottern LM et al (1995) Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Radiat Res 141(3):259–277

    Article  CAS  PubMed  Google Scholar 

  4. Bosetti C, Kolonel L, Negri E, Ron E, Franceschi S, Maso LD et al (2001) A pooled analysis of case-control studies of thyroid cancer. VI. Fish and shellfish consumption. Cancer Causes Control 12(4):375–382

    Article  CAS  PubMed  Google Scholar 

  5. Galanti MR, Ekbom A, Grimelius L, Yuen J (1997) Parental cancer and risk of papillary and follicular thyroid carcinoma. Br J Cancer 75(3):451–456

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Soliman PT, Wu D, Tortolero-Luna G, Schmeler KM, Slomovitz BM, Bray MS et al (2006) Association between adiponectin, insulin resistance, and endometrial cancer. Cancer 106(11):2376–2381

    Article  CAS  PubMed  Google Scholar 

  7. Antoniadis AG, Petridou ET, Antonopoulos CN, Dessypris N, Panagopoulou P, Chamberland JP et al (2011) Insulin resistance in relation to melanoma risk. Melanoma Res 21(6):541–546

    Article  CAS  PubMed  Google Scholar 

  8. Siddique A, Kowdley KV (2011) Insulin resistance and other metabolic risk factors in the pathogenesis of hepatocellular carcinoma. Clin Liver Dis 15(2):281–296

    Article  PubMed  Google Scholar 

  9. Djiogue S, Nwabo Kamdje AH, Vecchio L, Kipanyula MJ, Farahna M, Aldebasi Y, Seke Etet PF (2013) Insulin resistance and cancer: the role of insulin and IGFs. Endocr Relat Cancer 20(1):R1–R17

    Article  CAS  PubMed  Google Scholar 

  10. Rapp K, Schroeder J, Klenk J, Ulmer H, Concin H, Diem G et al (2006) Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria. Diabetologia 49(5):945–952

    Article  CAS  PubMed  Google Scholar 

  11. Fair AM, Dai Q, Shu XO, Matthews CE, Yu H, Jin F, Gao YT, Zheng W (2007) Energy balance, insulin resistance biomarkers, and breast cancer risk. Cancer Detect and Prev 31(3):214–219

    Article  CAS  Google Scholar 

  12. Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R (2009) Diabetes and cancer. Endocr Relat Cancer 16(4):1103–1123

    Article  CAS  PubMed  Google Scholar 

  13. Sara VR, Hall K (1990) Insulin-like growth factors and their binding proteins. Physiol Rev 70(3):591–614

    CAS  PubMed  Google Scholar 

  14. Jenkins PJ, Fairclough PD, Richards T, Lowe DG, Monson J, Grossman A et al (1997) Acromegaly, colonic polyps and carcinoma. Clin Endocrinol 47(1):17–22

    Article  CAS  Google Scholar 

  15. Harman SM, Metter EJ, Blackman MR, Landis PK, Carter HB (2000) Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein–3, and prostatespecific antigen as predictors of clinical prostate cancer. J Clin Endocrinol Metab 85(11):4258–4265

    Article  CAS  PubMed  Google Scholar 

  16. Yu H, Spitz MR, Mistry J, Gu J, Hong WK, Wu X (1999) Plasma levels of insulin-like growth factor-I and lung cancer risk: a case-control analysis. J Nat Cancer Inst 91(2):151–156

    Article  CAS  PubMed  Google Scholar 

  17. Malaguarnera R, Morcavallo A, Belfiore A (2012) The insulin and IGF-I pathway in endocrine glands carcinogenesis. J Oncol 2012:635614. doi:10.1155/2012/635614

    Article  PubMed Central  PubMed  Google Scholar 

  18. Zhao ZG, Guo XG, Ba CX et al (2012) Overweight, obesity and thyroid cancer risk: a meta-analysis of cohort studies. J Int Med Res 40:2041–2050

    Article  CAS  PubMed  Google Scholar 

  19. Kitahara CM, Platz EA, Freeman LE et al (2011) Obesity and thyroid cancer risk among U.S. men and women: a pooled analysis of five prospective studies. Cancer Epidemiol Biomarkers Prev 20:464–472

    Article  PubMed Central  PubMed  Google Scholar 

  20. Rinaldi S, Lise M, Clavel-Chapelon F et al (2012) Body size and risk of differentiated thyroid carcinomas: findings from the EPIC study. Int J Cancer 131:E1004–E1014

    Article  CAS  PubMed  Google Scholar 

  21. Chan BT, Lee AV (2008) Insulin receptor substrates (IRSs) and breast tumorigenesis. J Mammary Gland Biol Neoplasia 13(4):415–422

    Article  PubMed Central  PubMed  Google Scholar 

  22. Ouederni TB, Fadiel A, Stambouli N, Scalize TJ, Ben-Maiz H, Abid HK et al (2009) Influence of socioeconomic lifestyle factors and genetic polymorphism on type 2 diabetes occurrences among Tunisian Arab and Berber groups of Djerba Island. Pharmgenomics Pers Med 2:49–57

    PubMed Central  CAS  PubMed  Google Scholar 

  23. Ouederni TB, Sanches-Corona J, Flores-Martinez SE, Ben-Maiz H, Skhiri HA, Abid HK, Benammar-Elgaaied A (2009) The G1057D polymorphism of IRS-2 gene is not associated with type 2 diabetes and obese patients among ethnic groups in Tunisian population. Clin Biochem 42:1169–1173

    Article  CAS  PubMed  Google Scholar 

  24. Han SG, Park KH, Sung JS, Whang YM, Kim YJ, Shin ES et al (2008) Single nucleotide polymorphisms of IGFBP-3 gene and lung cancer risk in a Korean population. Lung Cancer 62:152–161

    Article  PubMed  Google Scholar 

  25. Hursting SD (2012) Minireview: the year in obesity and cancer. Mol Endocrinol 26(12):1961–1966

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Vucenik I, Stains JP (2012) Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann N Y Acad Sci 1271:37–43

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Pazaitou-Panayiotou K, Polyzos SA, Mantzoros CS (2013) Obesity and thyroid cancer: epidemiologic associations and underlying mechanisms. Obes Rev. doi:10.1111/obr.12070

    PubMed  Google Scholar 

  28. Kitahara CM, Platz EA, Park Y, Hollenbeck AR, Schatzkin A, Berrington de González A (2012) Body fat distribution, weight change during adulthood, and thyroid cancer risk in the NIH-AARP diet and health study. Int J Cancer 130(6):1411–1419

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Peterson E, De P, Nuttall R (2012) BMI, diet and female reproductive factors as risks for thyroid cancer: a systematic review. Plasone 7(1):1–10

    Google Scholar 

  30. Leitzmann MF, Brenner A, Moore SC, Koebnick C, Park Y, Hollenbeck A et al (2010) Prospective study of body mass index, physical activity and thyroid cancer. Int J Cancer 126(12):2947–2956

    PubMed Central  CAS  PubMed  Google Scholar 

  31. Clero E, Leux C, Brindel P, Truong T, Anger A, Teinturier C et al (2010) Pooled analysis of two case–control studies in New Caledonia and French Polynesia of body mass index and differentiated thyroid cancer: the importance of body surface area. Thyroid 20(11):1285–1293

    Article  PubMed  Google Scholar 

  32. Ayturk S, Gursoy A, Kut A, Anil C, Nar A, Tutuncu NB (2009) Metabolic syndrome and its components are associated with increased thyroid volume and nodule prevalence in a mild-to moderate iodine-deficient area. Eur J Endocrinol 161:599–605

    Article  CAS  PubMed  Google Scholar 

  33. Rezzonico JN, Rezzonico M, Pusiol E, Pitoia F, Niepomniszcze H (2009) Increased prevalence of insulin resistance in patients with differentiated thyroid carcinoma. Metab Syndr Relat Disord 7(4):375–380

    Article  CAS  PubMed  Google Scholar 

  34. Sahin M, Uçan B, Giniş Z, Topaloğlu O, Güngüneş A, Bozkurt NC et al (2013) Vitamin D3 levels and insulin resistance in papillary thyroid cancer patients. Med Oncol 30(2):589

    Article  PubMed  Google Scholar 

  35. Balkan F, Onal ED, Usluogullari A, Tuzun D, Ozdemir D, Inancli SS, Ersoy R, Cakir B (2013) Is there any association between insulin resistance and thyroid cancer? A case control study. 45(1):55–60

    Google Scholar 

  36. Hua SF, Xue FX, Zhang LZ, Wang YM, Zhao J (2008) Expression and activation of insulin receptor substrate-1 in endometrial carcinoma. Zhonghua Fu Chan Ke Za Zhi 43(6):437–441

    CAS  PubMed  Google Scholar 

  37. Nowakowska-Zajdel E, Mazurek U, Ziolko E, Niedworok E, Fatyga E, Kokot T et al (2011) Analysis of expression profile of gene encoding proteins of signal cascades activated by insulin-like growth factors in colorectal cancer. Int J Immunopathol Pharmacol 24(3):781–787

    CAS  PubMed  Google Scholar 

  38. Neuhausen SL, Brummel S, Ding YC, Singer CF, Pfeiler G, Lynch HT (2009) Genetic variation in insulin-like growth factor signaling genes and breast cancer risk among BRCA1 and BRCA2 carriers. Breast Cancer Res 11(5):1–12

    Article  Google Scholar 

  39. Hoang CD, Zhang X, Scott PD, Guillaume TJ, Maddaus MA, Yee D et al (2004) Selective activation of ınsulin receptor substrate-1 and ınsulin receptor substrate-2 in pleural mesothelioma cells: association with distinct malignant phenotypes. Cancer Res 64(20):7479–7485

    Article  CAS  PubMed  Google Scholar 

  40. Cayan F, Tok E, Aras-Ateş N, Ayaz L, Akbay E, Gen R et al (2010) Insulin receptor substrate-2 gene polymorphism: is it associated with endometrial cancer. Gynecol Endocrinol 26(5):378–382

    Article  CAS  PubMed  Google Scholar 

  41. Neuhausen SL, Slattery ML, Garner CP, Ding YC, Hoffman M, Brothman AR (2005) Prostate cancer risk and IRS-1, IRS-2, IGF-1, and INS polymorphisms: strong association of IRS-1 G972R variant and cancer risk. Prostate 64(2):168–174

    Article  CAS  PubMed  Google Scholar 

  42. Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M (2004) Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 363(9418):1346–1353

    Article  CAS  PubMed  Google Scholar 

  43. Chen W, Wang S, Tian T et al (2009) Phenotypes and genotypes of insulin-like growth factor 1, IGF binding protein-3 and cancer risk: evidence from 96 studies. Eur J Hum Genet 17(12):1668–1675

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. McGrath M, Lee IM, Buring J, De Vivo I (2011) Common genetic variation within IGF-1, IGFI-2, IGFBP-1, and IGFBP-3 and endometrial cancer risk. Gynecol Oncol 120(2):174–178

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Santosh V, Arivazhagan A, Sreekanthreddy P, Srinivasan H, Thota B, Srividya MR et al (2010) Grade-specific expression of insulin-like growth factor-binding proteins-2, -3, and -5 in astrocytomas: IGFBP-3 emerges as a strong predictor of survival in patients with newly diagnosed glioblastoma. Cancer Epidemiol Biomarkers Prev 19(6):1399–1408

    Article  CAS  PubMed  Google Scholar 

  46. Gigek CO, Leal MF, Lisboa LC, Silva PN, Chen ES, Lima EM et al (2010) Insulin-like growth factor binding protein-3 gene methylation and protein expression in gastric adenocarcinoma. Growth Horm IGF Res 20(3):234–238

    Article  CAS  PubMed  Google Scholar 

  47. Ressler S, Radhi J, Aigner T, Loo C, Zwerschke W, Sergi C (2009) Insulin-like growth factor-binding protein-3 in osteosarcomas and normal bone tissues. Anticancer Res 29(7):2579–2587

    CAS  PubMed  Google Scholar 

  48. Zhao L, He LR, Zhang R, Cai MY, Liao YJ, Qian D et al (2012) Low expression of IGFBP-3 predicts poor prognosis in patients with esophageal squamous cell carcinoma. Med Oncol 29:2669–2676

    Article  CAS  PubMed  Google Scholar 

  49. Safarinejad MR, Shafiei N, Safarinejad S (2011) Relationship of insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) gene polymorphism with the susceptibility to development of prostate cancer and influence on serum levels of IGF-I and IGFBP-3. Growth Horm IGF Res 21(3):146–154

    Article  CAS  PubMed  Google Scholar 

  50. Xu L, Mugartegui L, Li G, Sarlis NJ, Wei Q, Zafereo ME, Sturgis EM (2012) Functional polymorphisms in the insulin-like binding protein-3gene may modulate susceptibility to differentiated thyroid carcinoma in Caucasian Americans. Mol Carcinog 51(Suppl 1):E158–E167

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The study was supported by the Research Fund of the Trakya University Scientific Research Project (TUBAP-2011/35).

Conflict of interest

The authors declare no conflicts of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding

This research did not receive any specific grants from any funding agencies in the public, commercial, or not-for-profit sector.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, School of Medicine, University of Trakya, Edirne, Turkey

    Mustafa Akker & Ayhan Tosunoğlu

  2. Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, University of Trakya, Edirne, Turkey

    Sibel Güldiken

  3. Department of Biophysics, School of Medicine, University of Trakya, Edirne, Turkey

    Tammam Sipahi & Orkide Palabıyık

  4. Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Cerrahpasa Medicine, University of Istanbul, Istanbul, Turkey

    Özlem Çelik

  5. Department of Radiology, School of Medicine, University of Trakya, Edirne, Turkey

    Nermin Tunçbilek

  6. Department of General Surgery, School of Medicine, University of Trakya, Edirne, Turkey

    Atakan Sezer

  7. Department of Biostatistics, School of Medicine, University of Trakya, Edirne, Turkey

    Necdet Süt

  8. Ic Hastalıkları Anabilim Dalı, Endokrinoloji-Metabolizma Bilim Dalı, Tıp Fakultesi, Trakya Universitesi, Edirne, Turkey

    Sibel Güldiken

Authors
  1. Mustafa Akker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sibel Güldiken
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tammam Sipahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Orkide Palabıyık
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ayhan Tosunoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Özlem Çelik
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nermin Tunçbilek
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Atakan Sezer
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Necdet Süt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sibel Güldiken.

Appendix

Appendix

The study was supported by the Research Fund of the Trakya University Scientific Research Project (TUBAP-2011/35).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Akker, M., Güldiken, S., Sipahi, T. et al. Investigation of insulin resistance gene polymorphisms in patients with differentiated thyroid cancer. Mol Biol Rep 41, 3541–3547 (2014). https://doi.org/10.1007/s11033-014-3218-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3218-2

Keywords

Search

Navigation