Genes and SNPs Associated with Non-hereditary and Hereditary Colorectal Cancer

  • Nassiri, Mohammadreza (Department of Animal Science, Ferdowsi University of Mashhad) ;
  • Kooshyar, Mohammad Mahdi (Department of Hematology-Oncology, Mashhad University of Medical Sciences) ;
  • Roudbar, Zahra (Department of Animal Science, Ferdowsi University of Mashhad) ;
  • Mahdavi, Morteza (Department of Animal Science, Ferdowsi University of Mashhad) ;
  • Doosti, Mohammad (Department of Animal Science, Ferdowsi University of Mashhad)
  • Published : 2013.10.30


Background: Colorectal cancer is the third most common cancer in both men and women in the world and the second leading cause of cancer-related deaths. The incidence of colorectal cancer has increased in Iran in the past three decades and is now considered as a serious problem for our society. This cancer has two types hereditary and non-hereditary, 80% of cases being the latter. Considering that the relationship between SNPs with diseases is a concern, many researchers believed that they offer valuable markers for identifying genes responsible for susceptibility to common diseases. In some cases, they are direct causes of human disease. One SNP can increase risk of cancer, but when considering the rate of overlap and frequency of DNA repair pathways, it might be expected that SNP alone cannot affect the final result of cancer, although several SNPs together can exert a significant influence. Therefore identification of these SNPs is very important. The most important loci which include mutations are: MLH1, MSH2, PMS2, APC, MUTYH, SMAD7, STK11, $XRCC_3$, $DNMT_1$, MTHFR, Exo1, $XRCC_1$ and VDR. Presence of SNPs in these genes decreases or increases risk of colorectal cancer. Materials and Methods: In this article we reviewed the Genes and SNPs associated with non-hereditary and hereditary of colorectal cancer that recently were reported from candidate gene y, meta-analysis and GWAS studies. Results: As with other cancers, colorectal cancer is associated with SNPs in gene loci. Generally, by exploring SNPs, it is feasible to predict the risk of developing colorectal cancer and thus establishing proper preventive measures. Conclusions: SNPs of genes associated with colorectal cancer can be used as a marker SNP panel as a potential tool for improving cancer diagnosis and treatment planning.


Colorectal cancer;hereditary genes;non-hereditary genes;SNPs


  1. Alipour-Heidari M, Alavimajd H, Hajizadeh E, Azam K, Zali MR (2011). Relationship between DNMT1 gene's SNPs and colorectal cancer at Taleghani Hospital in Tehran. JQUMS, 15, 7-12.
  2. Alvarado MD, Jensen EH, Yeatman TJ (2006). The potential role of gene expression in the management of primary and metastatic colorectal cancer. Cancer Control, 13, 27-31.
  3. Azadeh S, Moghimi-Dehkordi B, Fatem SR, et al (2008). Colorectal cancer in Iran: an epidemiological study. Asian Pac J Cancer Prev, 9, 123-6.
  4. Berg M, Soreide K (2011). Genetic and Epigenetic Traits as Biomarkers in Colorectal Cancer. Int J Mol Sci, 12, 9426-39.
  5. Brenner BM, Rosenberg D (2010). High-throughput SNP/CGH approaches for the analysis of genomic instability in colorectal cancer. Mutat Res, 693, 46-52.
  6. Chen SP, Tsai ST, Jao SW, et al (2006). Single nucleotide polymorphisms of the APC gene and colorectal cancer risk: a case-control study in Taiwan. BMC Cancer, 6, 83.
  7. Dilmec F, Akkafa F, Ozgonul A, Uzunkoy A (2009). VDR gene BsmIG>Apolymorphism and risk of colorectal cancer in Sanliurfa province, Turkey. Turkiye Klinikleri J Med Sci, 29, 1386-91.
  8. Gopalan V, Smith RA, Nassiri MR, et al (2010). GAEC1 and colorectal cancer: a study of the relationships between a novel oncogene and clinicopathologic features. Human Pathology, 41, 1009-15.
  9. Hazra A, Chanock S, Giovannucci E, et al (2008). Large-scale evaluation of genetic variants in candidate genes for colorectal cancer risk in the nurses health study and the health professionals' follow-up study. Cancer Epidemiol Biomarkers Prev, 17, 311-9.
  10. Grahame Hardie D (2003). The AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology, 144, 5179-83.
  11. Haghighi MM, Mohebbi SR, Najjar Sadeghi R, et al (2008). Association between the 1793G>A MTHFR polymorphism and sporadic colorectal cancer in Iran. Asian Pac J Cancer Prev, 9, 659-62.
  12. Haghighi MM, Yaghoub TM, Irani SA, et al (2011). Association of C>T p757l polymorphism in EXO1 gene and risk of sporadic colorectal cancer in an Iranian population. Sci J Hamadan Univ Med Sci, 18, 45-9.
  13. Hampel H, Frankel WL, Martin E, et al (2005). Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer. N Enql J Med, 352, 1851-60.
  14. Hong S, Lim S, Li Allen, 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.
  15. Ionescu DN, Papachristou G, Schoen RE, et al (2005). Attenuated familial adenomatous polyposis: a case report with mixed features and review of genotype-phenotype correlation. Arch Pathol Lab Med, 129, 1401-4.
  16. Jelonek K, Gdowicz-Klosok A, Pietrowska M, et al (2010) Association between single- nucleotide polymorphisms of selected genes involved in the response to DNA damage and risk of colon, head and neck, and breast cancers in a Polish population. J Appl Genet, 51, 343-52.
  17. Kato S (2000). The function of vitamin D receptor in vitamin D action. J Biochem, 127, 717-22.
  18. Jin MJ, Chen K, Song L, et al (2005). The association of the DNA repair gene XRCC3 Thr241Met polymorphism with susceptibility to colorectal cancer in a Chinese population. Cancer Genetics and Cytogenetics, 163, 38-43.
  19. Kanai Y, Ushijima S, Nakanishi Y, Sakamoto M, Hirohashi S (2003). Mutation of the DNA methyltransferase (DNMT) 1 gene in human colorectal cancers. Cancer Letters, 192, 75-82.
  20. Kasahra M, Osawa K, Yoshida K, et al (2008). Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and smoking in a Japanese population. J Exp Clin Cancer Res, 27, 49.
  21. Ladiges W, Wiley J, MacAuley A (2003). Polymorphisms in the DNA repair gene XRCC1 and age-related disease. Mech Ageing Dev, 124, 27-32.
  22. Lam AK, Gopalana V, Nassiri MR (2001). Altered JS-2 expression in colorectal cancers and its clinical pathological relevance, Mol Oncol, 5, 475-81.
  23. Lee KM, Choi JY, Kang C, et al (2005). Genetic polymorphisms of selected DNA repair genes, estrogen and progesterone receptor status, and breast cancer risk. Clin Cancer Res, 11, 4620-6.
  24. Martha S, Herrick J, Curtin K, et al (2010). Increased risk of colon cancer associated with a genetic polymorphism of SMAD7. Cancer Res, 70, 1479-85.
  25. Martha S, Herrick J, Lundgreen AF, et al (2010). Genetic variation in a metabolic signaling pathway and colon and rectal cancer risk:mTOR, PTEN, STK11, RPKAA1, PRKAG2, TSC1, TSC2, PI3K and Akt1. Carcinogenesis, 31, 1604-11.
  26. Moghimi-Dehkordi B, Safaee A, Zali MR (2008). Prognostic factors in 1,138 Iranian colorectal cancer patients. Int J Colorectal Dis, 23, 683-8.
  27. Narayan S, Roy D (2003). Role of APC and DNA mismatch repair genes in the development of colorectal cancers. Molecular Cancer, 2, 41.
  28. Mrkonjic M, Raptis S, Green RC, et al (2007). MSH2-118T>C and MSH6-159C>T promoter polymorphisms and the risk of colorectal cancer. Carcinogenesis, 28, 2575-80.
  29. Mrkonjic M, Roslin NM, Greenwood CM, et al (2010). Specific variants in the MLH1 gene region may drive DNA methylation, loss of protein expression, and MSI-H colorectal cancer. PLoS ONE, 5, 13314.
  30. Muniz-Mendoza R, Ayala-Madrigal ML, Partida-Perez M, et al (2012). MLH1 and XRCC1 polymorphisms in Mexican patients with colorectal cancer. Genet Mol Res, 11, 2315-20.
  31. Ochs-Balcom HM, Cicek MS, Thompson CL, et al (2008). Association of vitamin D receptor gene variants, adiposity and colon cancer. Carcinogenesis, 29, 1788-93.
  32. Rowyda N, Wedam M (2011). Polymorphisms of the deoxyribonucleic acid (DNA) repair gene XRCC1 and risk of colon cancer in Saudi patients. Int J Med and Med Sci, 3, 282-8.
  33. Salajegheh A, Smith A, Kasem RA, et al (2011). Single nucleotide polymorphisms and mRNA expression of VEGF-A in papillary thyroid carcinoma: Potential markers for aggressive phenotypes. Eur J Surg Oncol, 37, 93-9.
  34. Shin KH, Shin JH, Kim JH, Park JG (2002). Mutational analysis of promoters of mismatch repair genes hMSH2 and hMLH1 in hereditary nonpolyposis colorectal cancer and early onset colorectal cancer patients: identification of three novel germline mutations in promoter of the hMSH2 gene. Cancer Res, 62, 2445.
  35. Smith RA, Salajegheh A, Weinstein S, Nassiri M, Lam AK (2011). Correlation between BRAF mutation and the clinicopathological parameters in papillary thyroid carcinoma with particular reference to follicular variant. Hum Patho, l42, 500-6.
  36. Tsuzuki T, Nakatsu, Y, Nakabeppu Y (2007). Significance of error-avoiding mechanisms for oxidative DNA damage in carcinogenesis. Cancer Sci, 98, 465-70.
  37. Tao H, Shinmura K, Suzuki M, et al (2008). Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population. Cancer Sci, 99, 355-60.
  38. Tenesa A, Farrington SM, Prendergast JD, et al (2008). Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. Nat Genet, 40, 631-7.
  39. Tsai MH, Tseng HC, Liu CS (2009). Interaction of Exo1 genotypes and smoking habit in oral cancer in Taiwan. Oral Oncol, 45, 90-4.
  40. Uitterlinden AG, Fang Y, van Meurs JB, van Leeuwen H, Pols HA (2004). Vitamin D receptor gene polymorphisms in relation to vitamin D related disease states. J Steroid Biochem Mol Biol, 891, 87-93.
  41. Vali U, Brandstrom M, Malin JM, Ellegren H (2008). Insertion-deletion polymorphisms (indels) as genetic markers in natural populations. BMC Genetics, 9, 8.
  42. Wang X, Tomso DJ, Liu X, (2004). Single nucleotide polymorphism in transcriptional regulatory regions and expression of environmentally responsive genes. Toxicol Appl Pharm, 207, 84-90.
  43. Whiffin N, Broderick P, Lubbe Steven JL, et al (2011). MLH1-93G>A is a risk factor for MSI colorectal cancer. Carcinogenesis, 32, 1157-61.
  44. Yamamoto H, Hanafusa H, Ouchida M, et al (2005). Single nucleotide polymorphisms in the EXO1 gene and risk of colorectal cancer in a Japanese population. Carcinogenesis, 26, 411-6.
  45. Yin G, Ming H, Zheng X, et al (2012). Methylenetetrahydrofolate reductase C677T gene polymorphism and colorectal cancer risk: a case-control study. Oncol Lett, 4, 365-9.
  46. Yu JH, Bigler J, Whitton J, Potter JD, Ulrich CM (2006). Mismatch repair polymorphisms and colorectal polyps: hMLH1-93G>A variant modifies risk associated with smoking. Am J Gastroenterol, 101, 1313-4.
  47. Zhao Y, Deng X, Wang Z, Wang Q, Liu Y (2012). Genetic polymorphisms of DNA repair genes XRCC1 and XRCC3 and risk of colorectal cancer in Chinese population. Asian Pac J Cancer Prev, 13, 665-9.

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