Document Type : Original Article

Authors

1 Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran

2 Assistant Professor, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran

3 Professor, Department of Biology, Faculty of Sciences, University of Isfahan, Isfahan, Iran

4 Associate Professor, Radiotherapy and Oncology Department, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background:Prostate cancer is increasing among Iranian men and gene polymorphisms may play a role in the development of prostate cancer. Insulin-like growth factor 1 (IGF1) gene polymorphisms have been deeply explored in different malignancies. In this study, we aimed to explore the association of IGF1 CA repeat length polymorphism with the risk of prostate cancer development in Isfahan province of Iran.
Method:The total blood of 100 prostate cancer patients and the equivalent matched control individuals were collected. DNA extraction was followed by IGF1 promoter polymorphism amplification. Genotyping was performed using polyacrylamide gel electrophoresis and sequencing was performed.
Results:According to the results, IGF1 promoter polymorphic site showed six different alleles ranging from 17-22 CA repeats among our studied population. Comparing SL heterozygotes with both homozygotes, a significant increase in RR value (RR=4.5, p=0.031) was observed. Although age adjustment and family history did not elevate the RR value, but a significantly elevated risk of prostate cancer (RR= 3.143, p=0.002) was shown when we compared SS patients with LL ones according to their BPH history.
Conclusion:In conclusion, carriers of (CA)17 allele could be at a higher risk of prostate cancer development and being SL heterozygotes could increase the risk of BPH development in our studied population.
 

Keywords

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int j cancer 2010; 127(12): 2893-917.
  2. Pakzad R, Rafiemanesh H, Ghoncheh M, Sarmad A, Salehiniya H, Hosseini S, et al. Prostate cancer in Iran: trends in incidence and morphological and epidemiological characteristics. Asian Pac J Cancer Prev 2016; 17(2):839-43.
  3. Sadjadi A, Nooraie M, Ghorbani A, Alimohammadian M, Zahedi MJ, Darvish-Moghadam S, et al. The incidence of prostate cancer in Iran: results of a population-based cancer registry. Arch Iran Med 2007; 10(4):481-5.
  4. Dianat SS, Margreiter M, Eckersberger E, Finkelstein J, Kuehas F, Herwig R, et al. Gene polymorphisms and prostate cancer: the evidence. BJU international 2009;104(11):1560-72.
  5. Fasching PA, Gayther S, Pearce L, Schildkraut JM, Goode E, Thiel F, et al. Role of genetic polymorphisms and ovarian cancer susceptibility. Mol Oncol 2009; 3(2):171-81.
  6. Coughlin SS, Hall IJ. A review of genetic polymorphisms and prostate cancer risk. Ann Epidemiol 2002; 12(3):182-96.;12(3):182-96.
  7. Canzian F, McKay JD, Cleveland RJ, Dossus L, Biessy C, Rinaldi S, et al. Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study. Br J Cancer 2006; 94(2):299-307.
  8. Shi J, Aronson KJ, Grundy A, Kobayashi LC, Burstyn I, Schuetz JM, et al. Polymorphisms of insulin-like growth factor 1 pathway genes and breast cancer risk. Front Oncol 2016; 6:136.
  9. Javadi M, Hematti S, Tavassoli M. Polymorphic CA repeat length in insulin-like growth factor 1 and risk of breast cancer in Iranian women. Medical Oncology 2012; 29(2):516-20.
  10. DiGiovanni J, Kiguchi K, Frijhoff A, Wilker E, Bol DK, Beltrán L, et al. Deregulated expression of insulin-like growth factor 1 in prostate epithelium leads to neoplasia in transgenic mice. Proc Natl Acad Sci U S A 2000; 97(7):3455-60.
  11. Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 2004; 363(9418):1346-53.
  12. Guo Q, Shen F, Zhang C, Yang X, Zhu HC, Zhang Q, et al. IGF-I CA19 repeat polymorphisms and cancer risk: a meta-analysis. Int J Clin Exp Med 2015; 8(11)20596-602.
  13. Batra J, Lose F, O'Mara T, Marquart L, Stephens C, Alexander K, et al. Association between Prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data. PLOS One. 2011;6(11):e26527.
  14. Cao DL, Ye DW, Dai B, Zhang HL, Shen YJ, Zhu Y, et al. Association of glutathione S-transferase T1 and M1 polymorphisms with prostate cancer susceptibility in populations of Asian descent: a meta-analysis. Oncotarget 2015; 6(34):35843-50.
  15. Weng H, Li S, Huang JY, He ZQ, Meng XY, Cao Y, et al. Androgen receptor gene polymorphisms and risk of prostate cancer: a meta-analysis. Sci Rep 2017; 7:40554.
  16. Zhang L, Shao N, Yu Q, Hua L, Mi Y, Feng N. Association between p53 Pro72Arg polymorphism and prostate cancer risk: a meta-analysis. J Biomed Res 2011; 25(1)25-32.
  17. Tsuchiya N, Wang L, Horikawa Y, Inoue T, Kakinuma H, Matsuura S, et al. CA repeat polymorphism in the insulin-like growth factor-I gene is associated with increased risk of prostate cancer and benign prostatic hyperplasia. Int J Oncol 2005; 26(1):225-31.
  18. Friedrichsen DM, Hawley S, Shu J, Humphrey M, Sabacan L, Iwasaki L, et al. IGF-I and IGFBP-3 polymorphisms and risk of prostate cancer. Prostate 2005; 65(1):44-51.
  19. Schildkraut JM, Demark-Wahnefried W, Wenham RM, Grubber J, Jeffreys AS, Grambow SC, et al. IGF1 (CA)19 repeat and IGFBP3 -202 A/C genotypes and the risk of prostate cancer in Black and White men. Cancer Epidemiol Biomarkers Prev 2005; 14(2):403-8.
  20. Chen C, Freeman R, Voigt LF, Fitzpatrick A, Plymate SR, Weiss NS. Prostate cancer risk in relation to selected genetic polymorphisms in insulin-like growth factor-I, insulin-like growth factor binding protein-3, and insulin-like growth factor-I receptor. Cancer Epidemiol Biomarkers Prev 2006; 15(12):2461-6.
  21. Li L, Cicek MS, Casey G, Witte JS. No association between genetic polymorphisms in IGF-I and IGFBP-3 and prostate cancer. Cancer Epidemiol Biomarkers Prev 2004; 13(3):497-8.
  22. Charlesworth D, Willis JH. The genetics of inbreeding depression. Nat Rev Genet 2009; 10(11):783-96.