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DNA Methylation in Human Genes for Schistosoma-Associated and Non-Schistosoma-Associated Bladder Cancer

Author Affiliations

  • 1 Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, SAUDI ARABIA
  • 2 Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, SAUDI ARABIA
  • 3 Faculty of Medicine, King Abdulaziz University, Jeddah, SAUDI ARABIA

Int. Res. J. Medical Sci., Volume 3, Issue (1), Pages 9-14, January,28 (2015)


This study is to analyze the usefulness of DNA methylation in eight candidate genes as tumor markers in bladder cancer of Schistosoma-associated and non-Schistosoma-associated bladder cancer. Methy Light assay was utilized to investigate the DNA methylation status of eight cancer related genes using DNA extracted from paraffin-embedded (FFPE) tissues of Saudi patients with bladder cancer of both Schistosoma-associated and non-Schistosoma-associated. These genes include TIMP3, RASSF1A, SLIT2, SOCS1, RUNX3, NEUROG1, IGF2 and CACNA1G. 85% of the investigated samples displayed detectable methylation level in one up to six genes. None of the 45 samples reacted positively to all genes. On other hand, only seven cases did not display any methylation. The correlations between methylation and the investigated genes were illustrated. SLIT2 was the most frequently methylated gene and none of the investigated cases showed methylation to all eight genes. Methylation in Saudi patients with non-Schistosoma-associated bladder cancer was higher than the Schistosoma-associated bladder cancer. There is a need for further work covering panel of genes to correlate them with further factors related to the clinical and pathological aspects.


  1. World health organization, EMRO_ report_ Schistosomiasis.pdf., (2014)
  2. Husain N. O. S. and Shumo A. I., Pattern and Risk Factors of Urinary Bladder Neoplasms in Sudanese patients in Khartoum State, Sudan, Sudan. J. Med. Sci.,3(3), 211-220 (2008)
  3. Garcia L.S., Diagnostic Medical Parasitology, 5th ed. Washington: ASM Press, (2007)
  4. Olfert S. M., Felknor S. A. and Delclos G. L., An Update Review of The Literature: Risk Factors for Bladder Cancer with Focus on Occupational Exposures, South. Med. J.,99(11), 1256-1263 (2006)
  5. Kirkali Z., Chan T., Murugesan M., Algaba F., Busch C. and Cheng L. et al., Bladder Cancer: Epidemiology, Staging and Grading, and Diagnosis, Urology., 66(6), 4-34 (2005)
  6. Kogevinas M., 't Mannetje A., Cordier S., Ranft U, González CA., Vineis P., et al., Occupation and Blood Cancer among Men in Western Europe, Cancer. Causes. Control., 14(10), 907-914 (2003)
  7. Mostafa M.H., Sheweita S.A. and Connor P.J., Relationship between Schistosomiasis and Bladder Cancer, Clin. Microbiol. Rev., 12(1), 97-111 (1999)
  8. Badawi A.F., Mostafa M.H., Probert A. and O'Connor P.J., Role of Schistosomiasis in Human Bladder Cancer: Evidence of Association, Aetiological Factors, and Basic Mechanisms of Carcinogenesis, Eur. J. Cancer. Prev., 4(1), 45–59 (1995)
  9. Mayer D.A. and Fried B., The Role of Helminth Infections in Carcinogenesis, Adv. Parasitol.,65, 239-296 (2007)
  10. Fried B., Reddy A. and Mayer D., Helminths in Human Carcinogenesis, Cancer. Lett.,305(2), 239-249 (2011)
  11. Tumor Registry Annual Report. King Faisal Cancer Centre Research Unit, Saudi Arabia., (2005)
  12. Cancer Incidence Report. The Ministry of Health, National Cancer Registry, Saudi Arabia., (2001)
  13. Johansson S.L. and Cohen S.M., Epidemiology and Etiology of Bladder Cancer, Sem. Surg. Oncol.,13(5), 291-298 (1997)
  14. Koraitim N.M., Metwalli N.E., Atta M.A. and El-Sadr A.A., Changing Age Incidence and Pathological Types of Schistosoma-Associated Bladder Carcinoma, J. Urol.,154(5), 1714-1716 (1995)
  15. Gibas Z. and Gibas L., Cytogenetics of Bladder Cancer, Cancer. Genet. Cytogenet., 95(1), 108–115 (1997)
  16. Mitelman F., Catalog of Chromosome Aberrations in Cancer, 5th ed. New York : Wiley-Liss, (1994)
  17. Hovey R.M., Chu L., Balazs M., DeVries S., Moore D. and Sauter G. et al., Genetic Alterations in Primary Bladder Cancers and Their Metastases, Cancer. Res.,58(16), 3555–3560 (1998)
  18. Bruch J., Wöhr G., Hautmann R., Mattfeldt T., Brüderlein S. and Möller P. et al., Chromosomal Changes During Progression of Transitional Cell Carcinoma of The Bladder and Delineation of The Amplified Interval on Chromosome Arm 8, Genes. Chromosom. Cancer.,23(2), 167–74 (1998)
  19. Simon R., Bürger H., Brinkschmidt C., Böcker W., Hertle L. and Terpe H. J., Chromosomal Aberrations Associated with Invasion in Papillary Superficial Bladder Cancer, J. Pathol.,185(4), 345–351 (1998)
  20. Richter J., Jiang F., Gorog J. P., Sartorius G., Egenter C. and Gasser T.C. et al., Marked Genetic Differences Between Stage pTa and Stage pT1 Papillary Bladder Cancer Detected by Comparative Genomic Hybridization, Cancer. Res.,57(14), 2860–2864 (1997)
  21. Kallioniemi A., Kallioniemi O. P., Citro G., Sauter G., DeVries S. and Kerschmann R. et al., Identification of Gains and Losses of DNA Sequences in Primary Bladder Cancer by Comparative Genomic Hybridization, Genes. Chromosom. Cancer.,12(3), 213–219 (1995)
  22. Voorter C., Joos S., Bringuier P.P., Vallinga M., Poddighe P. and Schalken J. et al., Detection of Chromosomal Imbalances in Transitional Cell Carcinoma of The Bladder by Comparative Genomic Hybridization, Am. J. Pathol., 146(6), 1341–1354 (1995)
  23. El-Rifai W., Kamel D., Larramendy M. L., Shoman S., Gad Y. and Baithun S. et al., DNA Copy Number Changes in Schistosoma-Associated and non-Schistosoma-Associated Bladder Cancer, Am. J. Pathol.,156(3), 871-878 (2000)
  24. Aly M.S. and Khaled H.M., Detection of C-erb B2 Gene Amplification in Bilharzial Associated Bladder Cancer Using Fluorescence in Situ Hybridization, Urol. Oncol.,22(6), 448-452 (2004)
  25. Gutiérrez M.I., Siraj A.K., Khaled H., Koon N., El-Rifai W. and Bhatia K., CpG Island Methylation in Schistosoma- and non-Schistosoma-Associated Bladder Cancer. Mod. Pathol.,17(10), 1268-1274 (2004)
  26. 6.Albertson D. G. and Pinkel D., Genomic Microarrays in Human Genetic Disease and Cancer, Hum. Mol. Gen.,12(2), R145-52 (2003)
  27. Armengol G., Eissa S., Lozano J. J., Shoman S., Sumoy L., Caball ´n M. R., et al., Genomic Imbalances in Schistosoma-associated and non-Schistosoma-Associated Bladder Carcinoma: An Array Comparative Genomic Hybridization Analysis, Cancer. Genet. Cytogenet., 177(1), 16-19 (2007)
  28. Vauhkonen H., Bo¨hling T., Eissa S., Shoman S. and Knuutila S., Can Bladder Adenocarcinomas be Distinguished from Schistosomiasis Associated Bladder Cancer by Using Comparative Genomic Hybridization Analysis?, Cancer. Genet. Cytogenet.,177(2), 153-157 (2007)
  29. Dallol A., Al-Ali W., Al-Shaibani A. and Al-Mulla F., Analysis of DNA Methylation in FFPE Tissues Using the MethyLight Technology, Methods. Mol. Biol.,724, 191-204 (2011)
  30. Wolff E. M., Liang G., Cortez C. C., Tsai Y. C., Castelao J. E. and Cortessis V.K. et al., RUNX3 Methylation Reveals That Bladder Tumors are Older in Patients with A History of Smoking, Cancer. Res., 68 (15), 6208-6214 (2008)
  31. Negraes P. D., Favaro F. P., Camargo J.L.V., Oliveira M.L.C.S., Goldberg J., Rainho C.A. et al., DNA Methylation Patterns in Bladder Cancer and Washing Cell Sediments: A Perspective for Tumor Recurrence Detection, BMC. Cancer.,8, doi:10.1186/1471-2407-8-238 (2008)
  32. Byun H.M., Wong H.L., Birnstein E.A., Wolff E.M., Liang G. and Yang A.S., Examination of IGF2 and H19 Loss of Imprinting in Bladder Cancer, Cancer. Res., 67(22), 10753-10758 (2007)
  33. Friedrich M. G., Toma M. I., Chun J. K. H. F.; Steuber T., Budäus L., Isbarn H., et al., DNA methylation on Urinalysis and as A Prognostic Marker in Urothelial Cancer of The Bladder, Urologe. A., 46(7), 761-768 (2007) German
  34. Cheng H., Deng Z., Wang Z., Zhang W. and Su J., MTHFR C677T Polymorphisms Are Associated with Aberrant Methylation of The IGF -2 Gene in Transitional Cell Carcinoma of The Bladder, J. Biomed. Res., 26(2), 77-83 (2012)
  35. Zhang Z., Wang S., Wang M., Tong N., Fu G. and Zhang Z., Genetic Variants in RUNX3 and Risk of Bladder Cancer: a Haplotype-Based Analysis, Carcinogenesis., 29(10), 1973-1978 (2008)
  36. Catto J.W., Azzouzi A. R., Rehman I., Feeley K. M., Cross S. S., Amira N., et al., Promoter Hypermethylation is Associated with Tumor Location, Stage, and Subsequent Progression in Transitional Cell Carcinoma, J. Clin. Oncol., 23(13), 2903–2910 (2005)
  37. Chan M. W., Chan L. W., Tang N. L., Lo K. W., Tong J. H., Chan A. W., et al., Frequent Hypermethylation of Promoter Region of RASSF1A in Tumor Tissues and Voided Urine of Urinary Bladder Cancer Patients, Int. J. Cancer., 104(5), 611–616 (2003)
  38. Dulaimi E., Uzzo R. G., Greenberg R. E., Al-Saleem T. and Cairns P., Detection of Bladder Cancer in Urine by A Tumor Suppressor Gene Hypermethylation Panel, Clin. Cancer. Res.,10(6), 1887–1893 (2004)
  39. Marsit C. J., Karagas M. R., Danaee H., Liu M., Andrew A., Schned A., et al. Carcinogen Exposure and Gene Promoter Hypermethylation in Bladder Cancer, Carcinogenesis., 27(1), 112–116 (2006)
  40. Maruyama R., Toyooka S., Toyooka K. O., Harada K., Virmani A. K., Zöchbauer-Müller S., et al. Aberrant Promoter Methylation Profile of Bladder Cancer and its Relationship to Clinicopathological Features, Cancer. Res.,61(24), 8659–8663 (2001)
  41. Kim W. J., Kim E. J., Jeong P., Quan C., Kim J., Li Q. L., et al., RUNX3 Inactivation by Point Mutations and Aberrant DNA Methylation in Bladder Tumors, Cancer. Res., 65(20), 9347–9354 (2005)
  42. Pu R. T., Laitala L. E. and Clark D. P., Methylation Profiling of Urothelial Carcinoma in Bladder Biopsy and Urine, Acta. Cytol., 50(5), 499-500 (2006)
  43. Hoque M. O., Begum S., Topaloglu O., Chatterjee A., Rosenbaum E., Van Criekinge W., et al., Quantitation of Promoter Methylation of Multiple Genes in Urine DNA and Bladder Cancer Detection, J. Natl. Cancer. Inst., 98(14), 996-1004 (2006)
  44. Hoque M. O., Begum S., Brait M., Jeronimo C., Zahurak M., Ostrow K. L., et al., Tissue Inhibitor of Metalloproteinases-3 Promoter Methylation is an Independent Prognostic Factor for Bladder Cancer, J. Urol., 179(2), 743–747 (2008)
  45. Zhu J. and Yao X., Use of DNA Methylation for Cancer Detection: Promises and Challenges, Int. J. Biochem. Cell. Biol., 41(1), 147-54 (2009)
  46. Vaughn C.P., Wilson A.R and Samowitz W.S., Quantitative Evaluation of CpG Island Methylation in Hyperplastic Polyps, Mod. Patho., 23(1), 151-156 (2010)
  47. Hughes L. A., Khalid-de Bakker C. A., Smits K. M., van den Brandt P. A., Jonkers D., Ahuja N., et al., The CpG Island Methylator Phenotype in Colorectal Cancer: Progress and Problems, Biochim. Biophys. Acta., 1825(1), 77-85 (2012)