Authors
1 Department of Genetics and Molecular Biology, and Pediatric Inherited Diseases Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2 Poursina Hakim Research Institute, Isfahan, Iran
3 Islamic Azad University of Iran, Shahreza Branch, Shahreza, Iran
Abstract
Background: To setup a non-invasive genetic screening method for colorectal cancer, we evaluated the promoter methylation status of secreted frizzled-related protein1 (sfrp1) in stool samples of colorectal cancer with respect to a series of healthy individuals, using methylation-specific polymerase chain reaction.
Materials and Methods: In stool samples from 25 patients with colorectal cancer and 25 healthy control subjects, isolated DNA was treated with sodium bisulfite and analyzed by methylation-specific polymerase chain reaction with primers specific for methylated or unmethylated promoter sequences of the SFRP1 gene.
Result: Methylation of the SFRP1 promoter was present in the stool DNA of patients with colorectal cancer. A sensitivity of 52% and specificity of 92% were achieved in the detection of colorectal neoplasia. The difference in methylation status of the SFRP1 promoter between the patients with colorectal neoplasia and the control group was statistically highly significant (P = 0.006).
Conclusions: The results indicate that this DNA stool test of methylation of the SFRP1 promoter is a sensitive and specific method. It is assumed that the test is potentially useful for the early detection of colorectal cancer.
Keywords
1. | Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics. CA Cancer J Clin 2007;57:43-66. |
2. | Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 2007;18:581-92. |
3. | Jemal A, Siegel R, Ward E, Murray T, Smigal C, Thun MJ. Cancer statistics. CA Cancer J Clin 2006;56:106-30. |
4. | Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancerstatistics 2003. CA Cancer J Clin 2003;53:5-26. |
5. | Hung KE, Chung DC. Colorectal cancer screening: Today and tomorrow. South Med J 2006;99:240-6; quiz 247-9. |
6. | Vernon SW. Participation in colorectal cancer screening: A review. J Natl Cancer Inst 1997;89:1406-22. |
7. | Schroy PC 3rd, Heeren TC. Patient perceptions of stool-based DNA testing for colorectal cancer screening. AmJ Prev Med 2005;28:208-14. |
8. | Mandel JS, Church TR, Ederer F, Bond JH. Colorectal cancer mortality: Effectiveness of biennial screening for fecal occult blood. J Natl Cancer Inst 1999;91:434-7. |
9. | Imperiale TF, Ransohoff DF, Itzkowitz SH. Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med 2004;351:2704-14. |
10. | Loktionov AO, Neill IK, Silvester KR. Quantiation of DNA from exfoliated colonocytes isolatedfrom human stool surface as a novel noninvasive screening test for colorectalcancer. Clin Cancer Res 1998;4:337-42. |
11. | Deenadayalu VP, Rex DK. Fecal-based DNA assays: A new, noninvasive approach to colorectal cancer screening. Cleve Clin J Med 2004;71:497-503. |
12. | Daraei A, Salehi R, Salehi M, Emami MH, Janghorbani M, Mohamadhashem F, et al. Effect of rs6983267 polymorphism in the 8q24 region and rs4444903 polymorphism in EGF gene on the risk of sporadiccolorectal cancer in Iranian population. Med Oncol 2012;291044-9. |
13. | Daraei A, Salehi R, Mohamadhashem F. DNA-methyltransferase 3B 39179 G > T polymorphism and risk of sporadic colorectal cancer in a subset of Iranian population. J Res Med Sci 2011;16:807-13. [PUBMED] |
14. | Daraei A, Salehi R, Mohamadhashem F. PTGS2 (COX2) -765G>C gene polymorphism and risk of sporadic colorectal cancer in Iranian population. Mol Biol Rep 2012;39:5219-24. |
15. | Mandel JS, Church TR, Bond JH. The effect of fecal occult-blood screening on the incidence of colorectal cancer. N Engl J Med 2000;343:1603-77. |
16. | Ahlquist DA, Shuber AP. Stool screening for colorectalcancer: Evolution from occult blood to molecularmarkers. Clin Chim Acta 2002;315:157-68. |
17. | Belshaw NJ, Elliott GO, Williams EA, Bradburn DM, Mills SJ, Mathers JC, et al. Use of DNA from human stools to detect aberrant CpG island methylation of genes implicated in colorectal cancer. Cancer Epidemiol Biomarkers Prev 2004;13:1495-501. |
18. | Leung WK, To KF, Man EP, Chan MW, Hui AJ, Ng SS, et al. Detection of hypermethylated DNA or cyclooxygenase-2 messenger RNA in fecal samples of patients with colorectal cancer or polyps. Am J Gastroenterol 2007;102:1070-6. |
19. | Kondo Y, Issa JP. Epigenetic changes in colorectal cancer. Cancer Metastasis Rev 2004;23:29-39. |
20. | Qi J, Zhu YQ, Luo J, Tao WH. Hypermethylation and expression regulation of secreted frizzled-related protein genes in colorectal tumor.World J Gastroenterol 2006;12:7113-7. |
21. | Feinberg AP, Vogelstein B. Hypomethylation distin-ishes genes of some human cancers from their normal counterparts. Nature 1983;301:89-92. |
22. | Feinberg AP, Tycko B. The history of cancer epigenetics. Nat Rev Cancer 2004;4:143-53. |
23. | Suzuki H, Gabrielson E, Chen W. A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat Genet 2002;31:141-9. |
24. | Qi J, Zhu YQ, Luo J, Tao WH. Hypermethylation and expression regulation of secreted frizzled-related protein genes in colorectal tumor. World J Gastroenterol. 2006;12:7113-7. |
25. | Huang ZH, LiL H, Yang F, Wang JF. Detection of aberrant methylation in fecal DNA as a molecular screening tool for colorectal cancer and precancerous lesions. World J Gastroenterol 2007;13:950-4. |
26. | Zou H, Molina JR, Harrington JJ, Osborn NK, Klatt KK, Romero Y, et al. Aberrant methylation of secreted frizzled-related protein genes in esophageal adenocarcinoma and Barretts esophagus. Int J Cancer 2005;116:584-91. |
27. | Ra Wagner JL. Cost-effectiveness of screening for common cancers. Cancer metastasis Rev 1997;16:281-94. |
28. | Shane E, Hendon, Jack A. Practices for colon cancer screening division of gastroenterology, University of South Alabama College of Medicine. Mobile AL. USA Keio J Med 2005;54:179-83. |
29. | Lang CA, Ransohoff DF. Fecal occult blood screening for colorectal cancer. Is mortality reduced by chance selection for screening colonoscopy? J Am Med Assoc 1994;271:1011-3. |
30. | Schroy PC, Heeren, TC. A comparative study of patient perceptions and screening preferences for stool-based DNA testing(SBDNA), fecal occult blood testing (FOBT), or colonoscopy (CS). Gastroenterology 2003;124:A481. |
31. | Fodde R, Smits R, Clevers H. APC, signal transduction and genetic instability in colorectal cancer. Nat Rev Cancer 2001;1:55-67. |
32. | Kawano Y, Kypta R. Secreted antagonists of the Wnt signaling pathway. J Cell Sci 2003;116:2627-34. |
33. | Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet 2002;3:415-28. |
34. | Jubb AM, Bell SM, Quirke P. Methylation and colorectal cancer. J Pathol 2001;195:111-34. |
35. | Muller HM, Oberwalder M, Fiegl H. Methylation changes in fecal DNA: A marker for colorectal cancer screening? Lancet 2004;363:1283-5. |
36. | Zhang, W., M. Bauer, R.S. Croner, J.O. Pelz, D. Lodygin, H. Hermeking, et al. DNA stool test for colorectal cancer: Hypermethylation of the secreted frizzled-related protein-1 gene. Dis. Colon Rectum 50, 2007:1618-26. |
37. | Azuara D, Rodriguez-Moranta F, de Oca J, Soriano-Izquierdo A, Mora J, Guardiola J, et al. Novel methylation panel for the early detection of colorectal tumors in stool DNA. Clinical colorectal cancer. 2010;9:168-76. |