Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Lack of Influence of the SMAD7 Gene rs2337107 Polymorphism on Risk of Colorectal Cancer in an Iranian Population

  • Akbari, Zahra (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Safari-Alighiarloo, Nahid (Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences) ;
  • Haghighi, Mahdi Montazer (Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Vahedi, Mohsen (Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences) ;
  • Mirtalebi, Hanieh (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Azimzadeh, Pedram (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Milanizadeh, Saman (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Shemirani, Atena Irani (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Nazemalhosseini-Mojarad, Ehsan (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Aghdaei, Hamid Asadzadeh (Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Zali, Mohammad Reza (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences)
  • Published : 2014.06.15
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Abstract

SMAD7 has been identified as a functional candidate gene for colorectal cancer (CRC). SMAD7 protein is a known antagonist of the transforming growth factor beta ($TGF-{\beta}$) signaling pathway which is involved in tumorigenesis. Polymorphisms in SMAD7 may thus alter cancer risk. The aim of this study was to investigate the influence of a SMAD7 gene polymorphism (rs2337107) on risk of CRC and clinicopathological features in an Iranian population. In total, 210 subjects including 105 patients with colorectal cancer and 105 healthy controls were recruited in our study. All samples were genotyped by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of colorectal cancer and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs2337107and the risk of colorectal cancer. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). Although there was not any association between genotypes and disorder, CT was the most common genotype in this population. This genotype prevalence was also higher in the patients with well grade (54.9%) and colon (72.0%) tumors. Our results provide the first evidence that this polymorphism is not a potential contributor to the risk of colorectal cancer and clinicopathological features in an Iranian population, and suggests the need of a large-scale case-control study to validate our results.

Keywords

References

  1. Azadeh S, Moghimi-Dehkordi B, Fatem S, et al (2007). Colorectal cancer in Iran: an epidemiological study. Asian Pac J Cancer Prev, 9, 123-6.
  2. Boulay JL, Mild G, Lowy A, et al (2003). SMAD7 is a prognostic marker in patients with colorectal cancer. Int J Cancer, 104, 446-9. https://doi.org/10.1002/ijc.10908
  3. Broderick P, Carvajal-Carmona L, Pittman AM, et al (2007). A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk. Nature Genetics, 39, 1315-7. https://doi.org/10.1038/ng.2007.18
  4. Derynck R, Akhurst RJ, Balmain A (2001). TGF-$\beta$ signaling in tumor suppression and cancer progression. Nature Genetics, 29, 117-29. https://doi.org/10.1038/ng1001-117
  5. Gaasenbeek M, Howarth K, Rowan AJ, et al (2006). Combined array-comparative genomic hybridization and single-nucleotide polymorphism-loss of heterozygosity analysis reveals complex changes and multiple forms of chromosomal instability in colorectal cancers. Cancer Res, 66, 3471-9. https://doi.org/10.1158/0008-5472.CAN-05-3285
  6. Green MR, Sambrook J (2012). Molecular cloning: a laboratory manual, Cold Spring Harbor Laboratory Press.
  7. Haerian MS, Haerian BS, Rooki H, et al (2014). Association of 8q24.21 rs10505477-rs6983267 haplotype and age at diagnosis of colorectal cancer. Asian Pac J Cancer Prev, 15, 369-74. https://doi.org/10.7314/APJCP.2014.15.1.369
  8. Haghighi MM, Vahedi M, Mohebbi SR, et al (2009). Comparison of survival between patients with hereditary non polyposis colorectal cancer (HNPCC) and sporadic colorectal cancer. Asian Pac J Cancer Prev, 10, 497-500.
  9. Halder S, Rachakonda G, Deane N, et al (2008). SMAD7 induces hepatic metastasis in colorectal cancer. Br J Cancer, 99, 957-65. https://doi.org/10.1038/sj.bjc.6604562
  10. Halder SK, Beauchamp RD, Datta PK (2005). SMAD7 induces tumorigenicity by blocking TGF-$\beta$-induced growth inhibition and apoptosis. Experimental Cell Res, 307, 231-46. https://doi.org/10.1016/j.yexcr.2005.03.009
  11. Hong S, Lim S, Li AG, et al (2007). SMAD7 binds to the adaptors TAB2 and TAB3 to block recruitment of the kinase TAK1 to the adaptor TRAF2. Nature Immunology, 8, 504-13. https://doi.org/10.1038/ni1451
  12. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  13. Jiang X, Castelao JE, Vandenberg D, et al (2013). Genetic variations in SMAD7 are associated with colorectal cancer risk in the colon cancer family registry. PloS one, 8, 60464. https://doi.org/10.1371/journal.pone.0060464
  14. Kirk BW, Feinsod M, Favis R, et al (2002). Single nucleotide polymorphism seeking long term association with complex disease. Nucleic Acids Res, 30, 3295-311. https://doi.org/10.1093/nar/gkf466
  15. Levy L, Hill CS (2006). Alterations in components of the TGF-beta superfamily signaling pathways in human cancer. Cytokine Growth Factor Rev, 17, 41-58. https://doi.org/10.1016/j.cytogfr.2005.09.009
  16. Li X, Yang X-x, Hu N-y, et al (2011). A risk-associated single nucleotide polymorphism of SMAD7 is common to colorectal, gastric, and lung cancers in a Han Chinese population. Molecular Biology Reports, 38, 5093-7. https://doi.org/10.1007/s11033-010-0656-3
  17. Lichtenstein P, Holm NV, Verkasalo PK, et al (2000). Environmental and heritable factors in the causation of cancer-analyses of cohorts of twins from Sweden, Denmark, and Finland. New Eng J Med, 343, 78-85. https://doi.org/10.1056/NEJM200007133430201
  18. Massague J (2008). TGF$\beta$ in cancer. Cell, 134, 215-30. https://doi.org/10.1016/j.cell.2008.07.001
  19. Milanizadeh S, Khanyaghma M, Haghighi MM, et al (2013). Molecular analysis of imperative polymorphisms of MLH1 gene in sporadic colorectal cancer. Cancer Biomark, 13, 427-32.
  20. Moghimi-Dehkordi B, Safaee A (2012). An overview of colorectal cancer survival rates and prognosis in Asia. World J Gastrointestinal Oncol, 4, 71. https://doi.org/10.4251/wjgo.v4.i4.71
  21. Nassiri M, Kooshyar MM, Roudbar Z, et al (2013). Genes and SNPs associated with non-hereditary and hereditary colorectal cancer. Asian Pac J Cancer Prev, 14, 5609-14. https://doi.org/10.7314/APJCP.2013.14.10.5609
  22. Pittman AM, Naranjo S, Webb E, et al (2009). The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression. Genome Res, 19, 987-93. https://doi.org/10.1101/gr.092668.109
  23. Rizzo A, Waldner MJ, Stolfi C, et al (2011). SMAD7 expression in T cells prevents colitis-associated cancer. Cancer Res, 71, 7423-32. https://doi.org/10.1158/0008-5472.CAN-11-1895
  24. Shemirani AI, Haghighi MM, Zadeh SM, et al (2011). Simplified MSI marker panel for diagnosis of colorectal cancer. Asian Pac J Cancer Prev, 12, 2101-4.
  25. Slattery ML, Herrick J, Curtin K, et al (2010). Increased risk of colon cancer associated with a genetic polymorphism of SMAD7. Cancer Res, 70, 1479-85. https://doi.org/10.1158/0008-5472.CAN-08-1792
  26. Song Q, Zhu B, Hu W, et al (2012). A common SMAD7 variant is associated with risk of colorectal cancer: evidence from a case-control study and a meta-analysis. PloS One, 7, 33318. https://doi.org/10.1371/journal.pone.0033318
  27. Stolfi C, Marafini I, De Simone V, et al (2013). The dual role of SMAD7 in the control of cancer growth and metastasis. Int J Molecular Sci, 14, 23774-90. https://doi.org/10.3390/ijms141223774
  28. Tenesa A, Dunlop MG (2009). New insights into the aetiology of colorectal cancer from genome-wide association studies. Nature Reviews Genetics, 10, 353-8.
  29. Tenesa A, Farrington SM, Prendergast JG, et al (2008). Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. Nature Genetics, 40, 631-7. https://doi.org/10.1038/ng.133
  30. Thompson CL, Plummer SJ, Acheson LS, et al (2009). Association of common genetic variants in SMAD7 and risk of colon cancer. Carcinogenesis, 30, 982-6. https://doi.org/10.1093/carcin/bgp086
  31. Tomlinson IP, Webb E, Carvajal-Carmona L, et al (2008). A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23. 3. Nature Genetics, 40, 623-30. https://doi.org/10.1038/ng.111
  32. Xu Y, Pasche B (2007). TGF-$\beta$ signaling alterations and susceptibility to colorectal cancer. Human Molecular Genetics, 16, 14-20. https://doi.org/10.1093/hmg/ddl486
  33. Yan X, Chen Y (2011). SMAD7: not only a regulator, but also a cross-talk mediator of TGF-beta signalling. Biochem J, 434, 1-10. https://doi.org/10.1042/BJ20101827

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