Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Is there an Association between Variants in Candidate Insulin Pathway Genes IGF-I, IGFBP-3, INSR, and IRS2 and Risk of Colorectal Cancer in the Iranian Population?

  • Karimi, Khatoon (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Mahmoudi, Touraj (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Karimi, Negar (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Dolatmoradi, Hesamodin (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Arkani, Maral (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Farahani, Hamid (Department of Physiology, School of Medicine, Qom University of Medical Sciences) ;
  • Vahedi, Mohsen (Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences) ;
  • Parsimehr, Elham (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Dabiri, Reza (Internal Medicine Department, Semnan University of Medical Sciences) ;
  • Nobakht, Hossein (Internal Medicine Department, Semnan University of Medical Sciences) ;
  • Asadi, Asadollah (Department of Biology, Faculty of Science, University of Mohaghegh Ardabili) ;
  • Zali, Mohammad Reza (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences)
  • Published : 2013.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Several epidemiological studies have shown associations between colorectal cancer (CRC) risk and type 2 diabetes and obesity. Any effects would be expected to be mediated through the insulin pathway. Therefore it is possible that variants of genes encoding components of the insulin pathway play roles in CRC susceptibility. In this study, we hypothesized that polymorphisms in the genes involving the insulin pathway are associated with risk of CRC. Materials and Methods: The associations of four single nucleotide polymorphisms (SNPs) in IGF-I (rs6214), IGFBP-3 (rs3110697), INSR (rs1052371), and IRS2 (rs2289046) genes with the risk of CRC were evaluated using a case-control design with 167 CRC cases and 277 controls by the PCR-RFLP method. Results: Overall, we observed no significant difference in genotype and allele frequencies between the cases and controls for the IGF-I, IGFBP-3, INSR, IRS2 gene variants and CRC before or after adjusting for confounders (age, BMI, sex, and smoking status). However, we observed that the IRS2 (rs2289046) GG genotype compared with AA+AG genotypes has a protective effect for CRC in normal weight subjects (p=0.035, OR=0.259, 95%CI= 0.074-0.907). Conclusions: These findings do not support plausible associations between polymorphic variations in IGF-I, IGFBP-3, INSR, IRS2 genes and risk of CRC. However, the evidence for a link between the IRS2 (rs2289046) variant and risk of CRC dependent on the BMI of the subjects, requires confirmation in subsequent studies with greater sample size.

Keywords

References

  1. Baroudi Ouederni T, Sanchez-Corona J, Flores Martinez SE, et al (2009). The G1057D polymorphism of IRS2 gene is not associated with type 2 diabetes and obese patients among ethnic groups in Tunisian population. Clin Biochem, 42, 1169-73. https://doi.org/10.1016/j.clinbiochem.2009.03.018
  2. Biddinger SB, Kahn CR (2006). From mice to men: insights into the insulin resistance syndromes. Annu Rev Physiol, 68, 123-58. https://doi.org/10.1146/annurev.physiol.68.040104.124723
  3. Bodhini D, Radha V, Deepa R, et al (2007). The G1057D polymorphism of IRS-2 gene and its relationship with obesity in conferring susceptibility to type 2 diabetes in Asian Indians. Int J Obes (Lond), 31, 97-102. https://doi.org/10.1038/sj.ijo.0803356
  4. Chapelle A (2004). Genetic predisposition to colorectal cancer. Nat Rev Cancer, 4, 769-80. https://doi.org/10.1038/nrc1453
  5. Chung YW, Han DS, Park KH, et al (2008). Insulin therapy and colorectal adenoma risk among patients with Type 2 diabetes mellitus: a case-control study in Korea. Dis Colon Rectum, 51, 593-7. https://doi.org/10.1007/s10350-007-9184-1
  6. Conne B, Stutz A, Vassalli JD (2000). The 3' untranslated region of messenger RNA: a molecular ''hotspot'' for pathology? Nat Med, 6, 637-41. https://doi.org/10.1038/76211
  7. Davies M, Gupta S, Goldspink G, et al (2006). The insulin-like growth factor system and colorectal cancer: clinical and experimental evidence. Int J Colorectal Dis, 21, 201-8. https://doi.org/10.1007/s00384-005-0776-8
  8. Deming SL, Ren Z, Cai Q, et al (2008). IGF-1 and IGF-2 genetic variation and breast cancer risk in Chinese Women: Results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev, 17, 255-7. https://doi.org/10.1158/1055-9965.EPI-07-2588
  9. Deming SL, Ren Z, Wen W, et al (2007). Genetic variation in IGF1, IGF-1R, IGFALS, and IGFBP3 in breast cancer survival among Chinese women: a report from the Shanghai Breast Cancer Study. Breast Cancer Res Treat, 104, 309-19. https://doi.org/10.1007/s10549-006-9420-8
  10. Feigelson HS, Teras LR, Diver WR, et al (2008). Genetic variation in candidate obesity genes ADRB2, ADRB3,GHRL, HSD11B1, IRS1, IRS2, and SHC1 and risk for breast cancer in the Cancer Prevention Study II. Breast Cancer Res, 10, 57.
  11. Feik E, Baierl A, Hieger B, et al (2010). Association of IGF1 and IGFBP3 polymorphisms with colorectal polyps and colorectal cancer risk. Cancer Causes Control, 21, 91-7. https://doi.org/10.1007/s10552-009-9438-4
  12. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917. https://doi.org/10.1002/ijc.25516
  13. Flores-Martinez SE, Islas-Andrade S, Machorro-Lazo MV, et al (2004). DNA polymorphism analysis of candidate genes for type 2 diabetes mellitus in a Mexican ethnic group. Ann Genet, 47, 339-48. https://doi.org/10.1016/j.anngen.2004.05.004
  14. Giovannucci E (1995). Insulin and colon cancer. Cancer Causes Control, 6, 164-79. https://doi.org/10.1007/BF00052777
  15. Giovannucci E (2001). Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr, 131, 3109-20. https://doi.org/10.1093/jn/131.11.3109S
  16. Gunter MJ, Hayes RB, Chatterjee N, et al (2007). Insulin resistance-related genes and advanced left-sided colorectal adenoma. Cancer Epidemiol Biomarkers Prev, 16, 703-8. https://doi.org/10.1158/1055-9965.EPI-06-0849
  17. Ho GY, Melman A, Liu SM, et al (2003). Polymorphism of the insulin gene is associated with increased prostate cancer risk. Br J Cancer, 88, 263-9. https://doi.org/10.1038/sj.bjc.6600747
  18. Kaaks R, Lukanova A (2001). Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proc Nutr Soc, 60, 91-106. https://doi.org/10.1079/PNS200070
  19. Khandwala HM, McCutcheon IE, Flyvbjerg A, et al (2000). The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev, 21, 215-44. https://doi.org/10.1210/edrv.21.3.0399
  20. Kohanski RA (1993). Insulin receptor autophosphorylation I. Autophosphorylation kinetics of the native receptor and its cytoplasmic kinase domain. Biochemistry, 32, 5766-72. https://doi.org/10.1021/bi00073a007
  21. Larsson SC, Orsini N, Wolk A (2005). Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst, 97, 1679-87. https://doi.org/10.1093/jnci/dji375
  22. Lautier C, EI Mkadem S, Renard E, et al (2003). Complex haplotypes of IRS2 gene are associated with severe obesity and reveal heterogeneity in the effect of Gly1057Asp mutation. Hum Genet, 113, 34-43.
  23. Lee DH, Kim JY, Lee MK, et al (2013). Effects of a 12-week home-based exercise program on the level of physical activity, insulin, and cytokines in colorectal cancer survivors: a pilot study. Support Care Cancer, [Epub ahead of print].
  24. Malodobra M, Pilecka A, Gworys B, et al (2011). Single nucleotide polymorphisms within functional regions of genes implicated in insulin action and association with the insulin resistant phenotype. Mol Cell Biochem, 349, 187-93. https://doi.org/10.1007/s11010-010-0673-5
  25. Moschos SJ, Mantzoros CS (2002). The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncol, 63, 317-32. https://doi.org/10.1159/000066230
  26. Nagel JM, Goke B (2006). Colorectal carcinoma screening in patients with type 2 diabetes mellitus. Z Gastroenterol, 44, 1153-65. https://doi.org/10.1055/s-2006-927132
  27. Neuhausen SL, Slattery ML, Garner CP, et al (2005). Prostate cancer risk and IRS1, IRS2, IGF1, and INS polymorphisms: Strong association of IRS1 G972R variant and cancer risk. Prostate, 64, 168-74. https://doi.org/10.1002/pros.20216
  28. Patel AV, Cheng I, Canzian F, et al (2008). 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, 3, 2578. https://doi.org/10.1371/journal.pone.0002578
  29. Pechlivanis S, Pardini B, Bermejo JL, et al (2007). Insulin pathway related genes and risk of colorectal cancer: INSR promoter polymorphism shows a protective effect. Endocr Relat Cancer, 14, 733-40. https://doi.org/10.1677/ERC-07-0107
  30. Pechlivanis S, Wagner K, Chang-Claude J, et al (2007). Polymorphisms in the insulin like growth factor 1 and IGF binding protein 3 genes and risk of colorectal cancer. Cancer Detect Prev, 31, 408-16. https://doi.org/10.1016/j.cdp.2007.10.001
  31. Pollak MN, Schernhammer ES, Hankinson SE (2004). Insulinlike growth factors and neoplasia. Nat Rev Cancer, 4, 505-18. https://doi.org/10.1038/nrc1387
  32. Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, et al (2004). Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet, 363, 1346-53. https://doi.org/10.1016/S0140-6736(04)16044-3
  33. Sarma AV, Dunn RL, Lange LA, et al (2008). Genetic polymorphisms in CYP17, CYP3A4, CYP19A1, SRD5A2, IGF-1, and IGFBP-3 and prostate cancer risk in African- American men: the flint men's health study. Prostate, 68, 296-305. https://doi.org/10.1002/pros.20696
  34. Slattery ML, Murtaugh M, Caan B, et al (2005). Energy balance, insulin-related genes and risk of colon and rectal cancer. Int J Cancer, 115, 148-54. https://doi.org/10.1002/ijc.20843
  35. Tamakoshi K, Wakai K, Kojima M, et al (2004). A prospective study of body size and colon cancer mortality in Japan: the JACC Study. Int J Obes Relat Metab Disord, 28, 551-8. https://doi.org/10.1038/sj.ijo.0802603
  36. Vella A, Bouatia-Naji N, Heude B, et al (2008). Association analysis of the IGF1 gene with childhood growth, IGF-1 concentrations and type 1 diabetes. Diabetologia, 51, 811-5. https://doi.org/10.1007/s00125-008-0970-7
  37. White MF (2006). Regulating insulin signaling and beta cell function through IRS proteins. Can J Physiol Pharmacol, 84, 725-37. https://doi.org/10.1139/y06-008
  38. White MF (1997). The insulin signaling system and the IRS proteins. Diabetologia, 40, 2-17. https://doi.org/10.1007/s001250051387
  39. Wong HL, Koh WP, Probst-Hensch NM, et al (2008). Insulinlike growth factor-1 promoter polymorphisms and colorectal cancer: a functional genomics approach. Gut, 57, 1090-6. https://doi.org/10.1136/gut.2007.140855
  40. Wong HL, Delellis K, Probst-Hensch N, et al (2005). A new single nucleotide polymorphism in the insulin-like growth factor I regulatory region associates with colorectal cancer risk in singapore chinese. Cancer Epidemiol Biomarkers Prev, 14, 144-51.
  41. Xuefen Su, Colditz GA, Willett WC, et al (2010). Genetic variation and circulating levels of IGF-I and IGFBP-3 in relation to risk of proliferative benign breast disease. Int J Cancer, 126, 180-90. https://doi.org/10.1002/ijc.24674
  42. Yam D, Fink A, Mashiah A, et al (1996). Hyperinsulinemia in colon, stomach and breast cancer patients. Cancer Lett, 104, 129-32. https://doi.org/10.1016/0304-3835(96)04211-5
  43. Yang YX, Hennessy S, Lewis JD (2004). Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients. Gastroenterol, 127, 1044-50. https://doi.org/10.1053/j.gastro.2004.07.011
  44. Zhang H, Kong WJ, Shan YQ, et al (2010). Protein kinase D activation stimulates the transcription of the insulin receptor gene. Mol Cell Endocrinol, 330, 25-32. https://doi.org/10.1016/j.mce.2010.07.022

Cited by

  1. Diagnostic Relevance of Overexpressed Serine Threonine Tyrosine Kinase/Novel Oncogene with Kinase Domain (STYK1/NOK) mRNA in Colorectal Cancer vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6685
  2. Lack of Association between Insulin Receptor Substrate2 rs1805097 Polymorphism and the Risk of Colorectal and Breast Cancer: A Meta-Analysis vol.9, pp.1, 2014, https://doi.org/10.1371/journal.pone.0086911
  3. An exon variant in insulin receptor gene is associated with susceptibility to colorectal cancer in women vol.36, pp.5, 2015, https://doi.org/10.1007/s13277-014-3010-x
  4. The Correlation Between Single Nucleotide Polymorphism Patterns and Colorectal Cancer in the Iranian Population vol.4, pp.3, 2016, https://doi.org/10.17795/acr-41527