Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Intronic Polymorphisms of the SMAD7 Gene in Association with Colorectal Cancer

  • Damavand, Behzad (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Derakhshani, Shaghayegh (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Saeedi, Nastaran (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Mohebbi, Seyed Reza (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) ;
  • Azimzadeh, Pedram (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Aghdaie, 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 : 2015.02.04
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Abstract

Based on genome-wide association studies (GWAS) a linkage between several variants such as single nucleotide polymorphisms (SNPs) in intron 3 of SMAD7 (mothers against decapentaplegic homolog7) were, rs12953717, rs4464148 and rs4939827 has been noted for susceptibility to colorectal cancer (CRC). In this study we investigated the relationship of rs12953717 and rs4464148 with risk of CRC among 487 Iranian individuals based on a case-control study. Genotyping of SNPs was performed by PCR-RFLP and for confirming the outcomes, 10% of genotyping cases were sequenced with RFLP. Comparing the case and control group, we have found significant association between the rs4464148 SNP and lower risk of CRC. The AG genotype showed decreased risk with and odds ratio of 0.635 (adjusted OR=0.635, 95% CI: 0.417-0.967, p=0.034). There was no significant difference in the distribution of SMAD7 gene rs12953717 TT genotype between two groups of the population evaluated (adjusted OR=1.604, 95% CI: 0.978-2.633, p=0.061). On the other hand, rs12953717 T allele showed a statistically significant association with CRC risk (adjusted OR=1.339, 95% CI: 1.017-1.764, p=0.037). In conclusion, we found a significant association between CRC risk and the rs4464148 AG genotype. Furthermore, the rs12953717 T allele may act as a risk factor. This association may be caused by alternative splicing of pre mRNA. Although we observed a strong association with rs4464148 GG genotype in affected women, we did not detect the same association in CRC male patients.

Keywords

References

  1. Akbari Z, Safari-Alighiarloo N, Haghighi MM, et al (2014). Lack of Influence of the SMAD7 gene rs2337107 polymorphism on risk of colorectal cancer in an Iranian population. Asian Pac J Cancer Prev, 15, 4437. https://doi.org/10.7314/APJCP.2014.15.11.4437
  2. Azimzadeh P, Romani S, Mohebbi SR, et al (2011). Interleukin-16 (IL-16) gene polymorphisms in Iranian patients with colorectal cancer. J Gastrointestin Liver Dis, 20, 371-6.
  3. Azimzadeh P, Romani S, Mohebbi SR, et al (2012). Association of polymorphisms in microRNA-binding sites and colorectal cancer in an Iranian population. Cancer Genetics, 205, 501-7. https://doi.org/10.1016/j.cancergen.2012.05.013
  4. 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. Nat Genet, 39, 1315-7. https://doi.org/10.1038/ng.2007.18
  5. Curtin K, Lin WY, George R, et al (2009). Meta association of colorectal cancer confirms risk alleles at 8q24 and 18q21. Cancer Epidemiol Biomarkers Prev, 18, 616-21. https://doi.org/10.1158/1055-9965.EPI-08-0690
  6. Dai J, Gu J, Huang M, et al (2012). GWAS-identified colorectal cancer susceptibility loci associated with clinical outcomes. Carcinogenesis, 33, 1327-31. https://doi.org/10.1093/carcin/bgs147
  7. Ginsburg GS, McCarthy JJ (2001). Personalized medicine: revolutionizing drug discovery and patient care. Trends Biotechnol, 19, 491-6. https://doi.org/10.1016/S0167-7799(01)01814-5
  8. Ho JW, Choi Sc, Lee Yf, et al (2011). Replication study of SNP associations for colorectal cancer in Hong Kong Chinese. Br J Cancer, 104, 369-75. https://doi.org/10.1038/sj.bjc.6605977
  9. Hoskins JM, Ong P-S, Keku TO, et al (2012). Association of eleven common, low-penetrance colorectal cancer susceptibility genetic variants at six risk loci with clinical outcome. PLoS ONE, 7, 41954. https://doi.org/10.1371/journal.pone.0041954
  10. Khorshidi F, Haghighi MM, Nazemalhosseini E, et al (2014). The Prostaglandin Synthase 2/cyclooxygenase 2 (PTGS2/COX2) rs5277 polymorphism does not influence risk of colorectal cancer in an Iranian population. Asian Pac J Cancer Prev, 15, 3507. https://doi.org/10.7314/APJCP.2014.15.8.3507
  11. Li X, Yang XX, Hu NY, et al (2011). A risk-associated single nucleotide polymorphism of SMAD7 is common to colorectal, gastric, and lung cancers in a Han Chinese population. Mol Biol Rep, 38, 5093-7. https://doi.org/10.1007/s11033-010-0656-3
  12. Loh YH, Mitrou PN, Wood A, et al (2011). SMAD7 and MGMT genotype variants and cancer incidence in the European prospective investigation into cancer and nutrition (EPIC)-norfolk study. Cancer Epidemiol, 35, 369-74. https://doi.org/10.1016/j.canep.2010.09.011
  13. Massague J (2008). TGFbeta in Cancer. Cell, 134, 215-30. https://doi.org/10.1016/j.cell.2008.07.001
  14. Mias G, Snyder M (2013). Personal genomes, quantitative dynamic omics and personalized medicine. Quantitative Biology, 1, 71-90. https://doi.org/10.1007/s40484-013-0005-3
  15. Middeldorp A, Jagmohan-Changur S, van Eijk R, et al (2009). Enrichment of low penetrance susceptibility loci in a Dutch familial colorectal cancer cohort. Cancer Epidemiol Biomarkers Prev, 18, 3062-7. https://doi.org/10.1158/1055-9965.EPI-09-0601
  16. Milanizadeh S, Khanyaghma M, Haghighi MM, et al (2013). Molecular analysis of imperative polymorphisms of MLH1 gene in sporadic colorectal cancer. Cancer Biomarkers, 13, 427-32.
  17. Miller SA, Dykes DD, Polesky HF (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res, 16, 1215. https://doi.org/10.1093/nar/16.3.1215
  18. Modrek B, Lee C (2002). A genomic view of alternative splicing. Nat Genet, 30, 13-9. https://doi.org/10.1038/ng0102-13
  19. Monteleone G, Boirivant M, Pallone F, et al (2008). TGF-[beta]1 and SMAD7 in the regulation of IBD. Mucosal Immunol, 1, 50-3. https://doi.org/10.1038/mi.2008.55
  20. Najjar Sadeghi R, Damavand B, Vahedi M, et al (2013). Detection of p53 common intron polymorphisms in patients with gastritis lesions from Iran. Asian Pac J Cancer Prev, 14, 91-6. https://doi.org/10.7314/APJCP.2013.14.1.91
  21. 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
  22. 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
  23. 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
  24. Tomlinson IPM, Webb E, Carvajal-Carmona L, et al (2008). A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3. Nat Genet, 40, 623-30. https://doi.org/10.1038/ng.111
  25. Watson JD (2013). Molecular biology of the gene: International edition, pearson education, limited.
  26. Wijnen JT, Brohet RM, van Eijk R, et al (2009). Chromosome 8q23.3 and 11q23.1 variants modify colorectal cancer risk in Lynch syndrome. Gastroenterology, 136, 131-7. https://doi.org/10.1053/j.gastro.2008.09.033
  27. Zhang H, Ma H, Xu Y, et al (2013). Association of SMAD7 rs12953717 polymorphism with cancer: a meta-analysis. PLoS One, 8, 58170. https://doi.org/10.1371/journal.pone.0058170

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