Medical Oncology

, Volume 29, Issue 2, pp 1044–1049 | Cite as

Effect of rs6983267 polymorphism in the 8q24 region and rs4444903 polymorphism in EGF gene on the risk of sporadic colorectal cancer in Iranian population

  • A. Daraei
  • R. Salehi
  • M. Salehi
  • M. H. Emami
  • M. Jonghorbani
  • F. Mohamadhashem
  • H. Tavakoli
Original Paper

Abstract

Colorectal cancer (CRC) is among the major causes of cancer-related morbidity, mortality, and human health problem worldwide. Single-nucleotide polymorphisms (SNPs) in different genes are reported to be effective in increased risk of CRC in different ethnic population. We conducted a case–control study in patients diagnosed with sporadic colorectal cancer (n = 115) and healthy controls based on colonoscopy evidences (n = 120).In this replicative study, we aimed to investigate the association of two previously reported polymorphisms, rs6983267 and rs4444903, with sporadic colorectal cancer in a subset of Iranian patients. Genotyping was performed via polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. A significant relation was found between rs6983267 variant in the 8q24 region and colorectal cancer. The distribution of G/G genotypes among sporadic CRC patients was more frequent than that in the control group (P value = 0.001). The frequency of the G allele in the colorectal cancer patient group was also higher than that in the control group (65% vs. 48%; P value = 0.001). Compared with GG genotype, individuals with G/T and T/T genotypes had lower risk to develop sporadic CRC (OR = 0.357, 95% CI = 0.201–0.635). For the rs4444903 SNP, no significant association (P value = 0.149) was found with colorectal cancer risk. In conclusion, our findings suggest that the 8q24 rs6983267 SNP may play a pivotal role in the development of sporadic CRC in Iranian population. Therefore, it may be included as a potential genetic susceptibility marker for sporadic CRC.

Keywords

Single-nucleotide polymorphisms Sporadic CRC EGF 8q24 region 

References

  1. 1.
    Jemal A, Siegel R, Ward E, Hao Y, Xu J, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58(2):71–96.PubMedCrossRefGoogle Scholar
  2. 2.
    Fahy B, Bold RJ. Epidemiology and molecular genetics of colorectal cancer. Surg Oncol. 1998;7(3–4):115–23.PubMedCrossRefGoogle Scholar
  3. 3.
    Cappell MS. Pathophysiology, clinical presentation, and management of colon cancer. Gastroenterol Clin North Am. 2008;37(1):1–24.PubMedCrossRefGoogle Scholar
  4. 4.
    Aaltonen L, Johns L, Jarvinen H, Mecklin JP, Houlston R. Explaining the familial colorectal cancer risk associated with mismatch repair (MMR)-deficient and MMR-stable tumors. Clin Cancer Res. 2007;13(1):356–61.PubMedCrossRefGoogle Scholar
  5. 5.
    Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, et al. Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med. 1998;338(21):1481–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Lau J, Ioannidis JP, Terrin N, Schmid CH, Olkin I. The case of the misleading funnel plot. BMJ. 2006;333(7568):597–600.PubMedCrossRefGoogle Scholar
  7. 7.
    Zintzaras E. The generalized odds ratio as a measure of genetic risk effect in the analysis and meta-analysis of association studies. Stat Appl Genet Mol Biol. 2010;9(1):50.Google Scholar
  8. 8.
    Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, et al. Environmental and heritable factors in the causation of cancer–analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000;343(2):78–85.PubMedCrossRefGoogle Scholar
  9. 9.
    Li D, Conti DV. Detecting gene-environment interactions using a combined case-only and case-control approach. Am J Epidemiol. 2009;169(4):497–504.PubMedCrossRefGoogle Scholar
  10. 10.
    Dong LM, Potter JD, White E, Ulrich CM, Cardon LR, et al. Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA. 2008;299(20):2423–36.PubMedCrossRefGoogle Scholar
  11. 11.
    Harismendy O, Frazer KA. Elucidating the role of 8q24 in colorectal cancer. Nat Genet. 2009;41(8):868–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Tuupanen S, Niittymaki I, Nousiainen K, Vanharanta S, Mecklin JP, et al. Allelic imbalance at rs6983267 suggests selection of the risk allele in somatic colorectal tumor evolution. Cancer Res. 2008;68(1):14–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Zanke BW, Greenwood CM, Rangrej J, Kustra R, Tenesa A, et al. Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat Genet. 2007;39(8):989–94.PubMedCrossRefGoogle Scholar
  14. 14.
    Wokolorczyk D, Gliniewicz B, Sikorski A, Zlowocka E, Masojc B, et al. A range of cancers is associated with the rs6983267 marker on chromosome 8. Cancer Res. 2008;68(23):9982–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Cicek MS, Slager SL, Achenbach SJ, French AJ, Blair HE, et al. Functional and clinical significance of variants localized to 8q24 in colon cancer. Cancer Epidemiol Biomarkers Prev. 2009;18(9):2492–500.PubMedCrossRefGoogle Scholar
  16. 16.
    Salomon DS, Brandt R, Ciardiello F, Normanno N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995;19(3):183–232.PubMedCrossRefGoogle Scholar
  17. 17.
    Price PM, Megyesi J, Saggi S, Safirstein RL. Regulation of transcription by the rat EGF gene promoter in normal and ischemic murine kidney cells. Am J Physiol. 1995;268(4 Pt 2):F664–70.PubMedGoogle Scholar
  18. 18.
    De Boer WI, Houtsmuller AB, Izadifar V, Muscatelli-Groux B, Van der Kwast TH, et al. Expression and functions of EGF, FGF and TGFbeta-growth-factor family members and their receptors in invasive human transitional-cell-carcinoma cells. Int J Cancer. 1997;71(2):284–91.PubMedCrossRefGoogle Scholar
  19. 19.
    Henson ES, Gibson SB. Surviving cell death through epidermal growth factor (EGF) signal transduction pathways: implications for cancer therapy. Cell Signal. 2006;18(12):2089–97.PubMedCrossRefGoogle Scholar
  20. 20.
    Siena S, Sartore-Bianchi A, Di Nicolantonio F, Balfour J, Bardelli A. Biomarkers predicting clinical outcome of epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer. J Natl Cancer Inst. 2009;101(19):1308–24.PubMedCrossRefGoogle Scholar
  21. 21.
    Spindler KL, Nielsen JN, Ornskov D, Brandslund I, Jakobsen A. Epidermal growth factor (EGF) A61G polymorphism and EGF gene expression in normal colon tissue from patients with colorectal cancer. Acta Oncol. 2007;46(8):1113–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Wu GY, Hasenberg T, Magdeburg R, Bonninghoff R, Sturm JW, et al. Association between EGF, TGF-beta1, VEGF gene polymorphism and colorectal cancer. World J Surg. 2009;33(1):124–9.PubMedCrossRefGoogle Scholar
  23. 23.
    McCarron SL, Bateman AC, Theaker JM, Howell WM. EGF +61 gene polymorphism and susceptibility to and prognostic markers in cutaneous malignant melanoma. Int J Cancer. 2003;107(4):673–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Kim YJ, Lee HS, Im JP, Min BH, Kim HD, et al. Association of transforming growth factor-beta1 gene polymorphisms with a hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection. Exp Mol Med. 2003;35(3):196–202.PubMedGoogle Scholar
  25. 25.
    Vishnoi M, Pandey SN, Modi DR, Kumar A, Mittal B. Genetic susceptibility of epidermal growth factor +61A>G and transforming growth factor beta1–509C>T gene polymorphisms with gallbladder cancer. Hum Immunol. 2008;69(6):360–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Gao LB, Wei YS, Zhou B, Wang YY, Liang WB, et al. No association between epidermal growth factor and epidermal growth factor receptor polymorphisms and nasopharyngeal carcinoma. Cancer Genet Cytogenet. 2008;185(2):69–73.PubMedCrossRefGoogle Scholar
  27. 27.
    Ribeiro R, Soares A, Pinto D, Catarino R, Lopes C, et al. EGF genetic polymorphism is associated with clinical features but not malignant phenotype in neurofibromatosis type 1 patients. J Neurooncol. 2007;81(3):225–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Araujo AP, Ribeiro R, Pinto D, Pereira D, Sousa B, Ma, et al. Epidermal growth factor genetic variation, breast cancer risk, and waiting time to onset of disease. DNA Cell Biol. 2009;28(5):265–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Amundadottir LT, Sulem P, Gudmundsson J, Helgason A, Baker A, et al. A common variant associated with prostate cancer in European and African populations. Nat Genet. 2006;38(6):652–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Berndt SI, Potter JD, Hazra A, Yeager M, Thomas G, et al. Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk. Hum Mol Genet. 2008;17(17):2665–72.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • A. Daraei
    • 1
  • R. Salehi
    • 1
  • M. Salehi
    • 1
  • M. H. Emami
    • 2
    • 3
  • M. Jonghorbani
    • 4
  • F. Mohamadhashem
    • 1
  • H. Tavakoli
    • 2
    • 3
  1. 1.Department of Biomedical Sciences, School of MedicineIsfahan University of Medical SciencesIsfahanIran
  2. 2.Isfahan University of Medical SciencesIsfahanIran
  3. 3.Poursina Hakim Research InstituteIsfahanIran
  4. 4.Department of Epidemiology and Biostatistics, School of Public HealthIsfahan University of Medical SciencesIsfahanIran

Personalised recommendations