Correlation of Breast Cancer with the Epstein Bar Virus and Human Cytomegalovirus Frequency and the Expression of Estrogen Receptor-Beta and IL-6 Receptor in Iraqi Women
Background and Purpose: In Iraq, breast cancer is the common type of female malignancy. Increasing indication in the past 10 years proposes that Epstein-Barr virus (EBV) and cytomegalovirus (HCMV) are related with some human malignancies including breast cancer. The part of EBV and HCMV in breast cancer is still debatable. Unraveling this relationship is potentially?essential for better understanding of breast cancer etiology, early recognition and possibly inhibition of breast cancer The purpose of the current study is to detect the correlation between EBV,?HCMV and breast cancer in Iraqi women and expression of ERB and IL-6R in breast tissues. Patients and Methods: The study was done on paraffin-embedded?tissues of eighty Iraqi patients with breast cancer in addition to twenty normal breast tissues as controls. Both controls and breast cancer mass?are?divided into two sections, one for DNA extraction and amplification by real time PCR for detect EBV and HCMV occurrence while the other section processed for protein expression (IL-6R, ERB) by immunohistochemistry technique (IHC). Results: The result showed that 18/80 (22.5%) and 5/80 (6.25%) sample from breast cancer were positive for EBV and HCMV respectively, with the?p-value?= 0.062 and 0.597 and the results of IHC for IL-6R and ERB expression in patients with breast cancer were 37/80 (46.25%) and 30/80 (37.5%)?p-value?=?(0.274 and 0.381) respectively. Conclusions: Our findings suggest that EBV might have a role in the pathogenesis of breast cancer and absence this role between HCMV with breast cancer. These findings were based mainly on EBV, HCMV detection by PCR technique. So,?the rolesof these viruses in the development of breast cancer remain unclear.
References
[1]
Parkin, D.M. (2006) The Global Health Burden of Infection-Associated Cancers in the Year 2002. International Journal of Cancer, 118, 3030-3044. https://doi.org/10.1002/ijc.21731
Lax, A.J. (2005) Bacterial Toxins and Cancer—A Case to Answer? Nature Reviews Microbiology, 3, 343-349. https://doi.org/10.1038/nrmicro1130
[4]
Tamburini, J., Grimaldi, D., Chiche, J.-D., Bricaire, F. and Bossi, P. (2007) Cytokine Pattern in Kaposi’s Sarcoma Associated with Immune Restoration Disease in HIV and Tuberculosis Co-Infected Patients. AIDS, 21, 1980-1983. https://doi.org/10.1097/QAD.0b013e3282efa62c
[5]
Ohshima, H. and Bartsch, H. (1994) Chronic Infections and Inflammatory Processes as Cancer Risk Factors: Possible Role of Nitric Oxide in Carcinogenesis. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 305, 253-264. https://doi.org/10.1016/0027-5107(94)90245-3
[6]
Jemal, A., Bray, F., Center, M.M., Ferlay, J., Ward, E. and Forman, D. (2011) Global Cancer Statistics. CA: A Cancer Journal for Clinicians, 61, 69-90. https://doi.org/10.3322/caac.20107
[7]
Hennighausen, L. (2000) Mouse Models for Breast Cancer. Breast Cancer Research, 2, 2. https://doi.org/10.1186/bcr20
[8]
Richardson, A. (1997) Is Breast Cancer Caused by Late Exposure to a Common Virus? Medical Hypotheses, 48, 491-497. https://doi.org/10.1016/S0306-9877(97)90118-3
[9]
Yasui, Y., Potter, J.D., Stanford, J.L., Rossing, M.A., Winget, M.D., Bronner, M., et al. (2001) Breast Cancer Risk and “Delayed” Primary Epstein-Barr Virus Infection. Cancer Epidemiology and Prevention Biomarkers, 10, 9-16.
[10]
Alibek, K., Kakpenova, A., Mussabekova, A., Sypabekova, M. and Karatayeva, N. (2013) Role of Viruses in the Development of Breast Cancer. Infectious Agents and Cancer, 8, 32. https://doi.org/10.1186/1750-9378-8-32
[11]
Harkins, L.E., Matlaf, L.A., Soroceanu, L., Klemm, K., Britt, W.J., Wang, W., et al. (2010) Detection of Human Cytomegalovirus in Normal and Neoplastic Breast Epithelium. Herpesviridae, 1, 8. https://doi.org/10.1186/2042-4280-1-8
[12]
Cox, B., Richardson, A., Graham, P., Gislefoss, R., Jellum, E. and Rollag, H. (2010) Breast Cancer, Cytomegalovirus and Epstein-Barr Virus: A Nested Case-Control Study. British Journal of Cancer, 102, 1665-1669. https://doi.org/10.1038/sj.bjc.6605675
[13]
Dziurzynski, K., Chang, S.M., Heimberger, A.B., Kalejta, R.F., McGregor Dallas, S.R., Smit, M., et al. (2012) Consensus on the Role of Human Cytomegalovirus in Glioblastoma. Neuro-Oncology, 14, 246-255. https://doi.org/10.1093/neuonc/nor227
[14]
Zhu, H., Shen, Y. and Shenk, T. (1995) Human Cytomegalovirus IE1 and IE2 Proteins Block Apoptosis. Journal of Virology, 69, 7960-7970.
[15]
Soderberg-Nauclér, C. (2008) HCMV Microinfections in Inflammatory Diseases and Cancer. Journal of Clinical Virology, 41, 218-223. https://doi.org/10.1016/j.jcv.2007.11.009
[16]
Michaelis, M., Doerr, H.W. and Cinatl, J. (2009) The Story of Human Cytomegalovirus and Cancer: Increasing Evidence and Open Questions. Neoplasia, 11, 1-19. https://doi.org/10.1593/neo.81178
[17]
Soroceanu, L. and Cobbs, C.S. (2011) Is HCMV a Tumor Promoter? Virus Research, 157, 193-203. https://doi.org/10.1016/j.virusres.2010.10.026
[18]
Baryawno, N., Rahbar, A., Wolmer-Solberg, N., Taher, C., Odeberg, J., Darabi, A., et al. (2011) Detection of Human Cytomegalovirus in Medulloblastomas Reveals a Potential Therapeutic Target. The Journal of Clinical Investigation, 121, 4043-4055. https://doi.org/10.1172/JCI57147
[19]
Luqmani, Ya. and Shousha, S. (1995) Presence of Epstein-Barr-Virus in Breast-Carcinoma. International Journal of Oncology, 6, 899-903. https://doi.org/10.3892/ijo.6.4.899
[20]
Labrecque, L.G., Barnes, D.M., Fentiman, I.S. and Griffin, B.E. (1995) Epstein-Barr Virus in Epithelial Cell Tumors: A Breast Cancer Study. Cancer Research, 55, 39-45.
[21]
Chu, J.-S., Chen, C.-C. and Chang, K.-J. (1998) In Situ Detection of Epstein-Barr Virus in Breast Cancer. Cancer Letters, 124, 53-57. https://doi.org/10.1016/S0304-3835(97)00449-7
[22]
Glaser, S.L., Ambinder, R.F., DiGiuseppe, J.A., Horn-Ross, P.L. and Hsu, J.L. (1998) Absence of Epstein-Barr Virus EBER-1 Transcripts in an Epidemiologically Diverse Group of Breast Cancers. International Journal of Cancer, 75, 555-558. https://doi.org/10.1002/(SICI)1097-0215(19980209)75:4<555::AID-IJC10>3.0.CO;2-8
[23]
Bonnet, M., Guinebretiere, J.-M., Kremmer, E., Grunewald, V., Benhamou, E., Contesso, G., et al. (1999) Detection of Epstein-Barr Virus in Invasive Breast Cancers. Journal of the National Cancer Institute, 91, 1376-1381. https://doi.org/10.1093/jnci/91.16.1376
[24]
Joshi, D., Quadri, M., Gangane, N., Joshi, R. and Gangane, N. (2009) Association of Epstein Barr Virus Infection (EBV) with Breast Cancer in Rural Indian Women. PLoS One, 4, e8180. https://doi.org/10.1371/journal.pone.0008180
[25]
He, J.-R., Tang, L.-Y., Yu, D.-D., Su, F.-X., Song, E.-W., Lin, Y., et al. (2011) Epstein-Barr Virus and Breast Cancer: Serological Study in a High-Incidence Area of Nasopharyngeal Carcinoma. Cancer Letters, 309, 128-136. https://doi.org/10.1016/j.canlet.2011.05.012
[26]
Perrigoue, J.G., Den Boon, J.A., Friedl, A., Newton, M.A., Ahlquist, P. and Sugden, B. (2005) Lack of Association between EBV and Breast Carcinoma. Cancer Epidemiology and Prevention Biomarkers, 14, 809-814. https://doi.org/10.1158/1055-9965.EPI-04-0763
[27]
Bahnassy, A., Zekri, A., Asaad, N., El-Houssini, S., Khalid, H., Sedky, L., et al. (2006) Epstein-Barr Viral Infection in Extranodal Lymphoma of the Head and Neck: Correlation with Prognosis and Response to Treatment. Histopathology, 48, 516-528. https://doi.org/10.1111/j.1365-2559.2006.02377.x
[28]
Mohamed, W.S., Mohamed, M.A. and Omar, M.M. (2007) Possible Involvement of Epstein-Barr Virus (EBV) in Pathogenesis and Prognosis of Female Breast Infiltrating Duct Carcinoma: Clinicopathological, Immunohistochemical and Molecular Study. The Egyptian Society of Medical Microbiology, 16, 403-414.
[29]
Fawzy, S., Sallam, M. and Awad, N.M. (2008) Detection of Epstein-Barr Virus in Breast Carcinoma in Egyptian Women. Clinical Biochemistry, 41, 486-492. https://doi.org/10.1016/j.clinbiochem.2007.12.017
[30]
Magrath, I. and Bhatia, K. (1999) Breast Cancer: A New Epstein-Barr Virus-Associated Disease? Journal of the National Cancer Institute, 91, 1349-1350. https://doi.org/10.1093/jnci/91.16.1349
[31]
Fina, F., Romain, S., Ouafik, L.H., Palmari, J., Ayed, F.B., Benharkat, S., et al. (2001) Frequency and Genome Load of Epstein-Barr Virus in 509 Breast Cancers from Different Geographical Areas. British Journal of Cancer, 84, 783-790. https://doi.org/10.1054/bjoc.2000.1672
[32]
Xue, S., Lampert, I., Haldane, J., Bridger, J. and Griffin, B. (2003) Epstein-Barr Virus Gene Expression in Human Breast Cancer: Protagonist or Passenger? British Journal of Cancer, 89, 113. https://doi.org/10.1038/sj.bjc.6601027
[33]
Mazouni, C., Fina, F., Romain, S., Ouafik, L., Bonnier, P., Brandone, J., et al. (2011) Epstein-Barr Virus as a Marker of Biological Aggressiveness in Breast Cancer. British Journal of Cancer, 104, 332-337. https://doi.org/10.1038/sj.bjc.6606048
[34]
Stewart, T., Tsai, S.-C., Grayson, H., Henderson, R. and Opelz, G. (1995) Incidence of De-Novo Breast Cancer in Women Chronically Immunosuppressed after Organ Transplantation. The Lancet, 346, 796-798. https://doi.org/10.1016/S0140-6736(95)91618-0
[35]
Savu, A., Potter, J., Li, S. and Yasui, Y. (2008) Breast Cancer and Microbial Cancer Incidence in Female Populations around the World: A Surprising Hyperbolic Association. International Journal of Cancer, 123, 1094-1099.
[36]
Hjalgrim, H., Askling, J., Sorensen, P., Madsen, M., Rosdahl, N., Storm, H.H., et al. (2000) Risk of Hodgkin’s Disease and Other Cancers after Infectious Mononucleosis. Journal of the National Cancer Institute, 92, 1522-1528. https://doi.org/10.1093/jnci/92.18.1522
[37]
Kamranvar, S. and Masucci, M. (2011) The Epstein-Barr Virus Nuclear Antigen-1 Promotes Telomere Dysfunction via Induction of Oxidative Stress. Leukemia, 25, 1017-1025. https://doi.org/10.1038/leu.2011.35
[38]
Straat, K., Liu, C., Rahbar, A., Zhu, Q., Liu, L., Wolmer-Solberg, N., et al. (2009) Activation of Telomerase by Human Cytomegalovirus. Journal of the National Cancer Institute, 101, 488-497. https://doi.org/10.1093/jnci/djp031
[39]
Perkins, R.S., Sahm, K., Marando, C., Dickson-Witmer, D., Pahnke, G.R., Mitchell, M., et al. (2006) Analysis of Epstein-Barr Virus Reservoirs in Paired Blood and Breast Cancer Primary Biopsy Specimens by Real Time PCR. Breast Cancer Research, 8, R70. https://doi.org/10.1186/bcr1627
[40]
Khan, G., Philip, P.S., Al Ashari, M., Houcinat, Y. and Daoud, S. (2011) Localization of Epstein-Barr Virus to Infiltrating Lymphocytes in Breast Carcinomas and Not Malignant Cells. Experimental and Molecular Pathology, 91, 466-470. https://doi.org/10.1016/j.yexmp.2011.04.018
[41]
Virus, E.-B. and Humans, I.W. (1997) GotEoCRt, Cancer IAfRo. Epstein-Barr Virus and Kaposi’s Sarcoma, Herpesvirus/Human Herpesvirus. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, 70.
[42]
Hsu, J.L. and Glaser, S.L. (2000) Epstein-Barr Virus-Associated Malignancies: Epidemiologic Patterns and Etiologic Implications. Critical Reviews in Oncology/Hematology, 34, 27-53. https://doi.org/10.1016/S1040-8428(00)00046-9
[43]
Gulley, M.L. (2001) Molecular Diagnosis of Epstein-Barr Virus-Related Diseases. The Journal of Molecular Diagnostics, 3, 1-10. https://doi.org/10.1016/S1525-1578(10)60642-3
[44]
Niedobitek, G., Meru, N. and Delecluse, H.J. (2001) Epstein-Barr Virus Infection and Human Malignancies. International Journal of Experimental Pathology, 82, 149-170. https://doi.org/10.1111/j.1365-2613.2001.iep190.x
[45]
Junker, A.K., Thomas, E.E., Radcliffe, A., Forsyth, R.B., Davidson, A.G.F. and Rymo, L. (1991) Epstein-Barr Virus Shedding in Breast Milk. The American Journal of the Medical Sciences, 302, 220-223. https://doi.org/10.1097/00000441-199110000-00005
[46]
Glenn, W., Heng, B., Delprado, W., Iacopetta, B. and Whitaker, N. (2012) Epstein-Barr Virus, Human Papillomavirus and Mouse Mammary Tumour Virus as Multiple Viruses in Breast Cancer. PLoS One, 7, e48788. https://doi.org/10.1371/journal.pone.0048788
[47]
Giardini, R., Piccolo, C. and Rilke, F. (1992) Primary Non-Hodgkin’s Lymphomas of the Female Breast. Cancer, 69, 725-735. https://doi.org/10.1002/1097-0142(19920201)69:3<725::AID-CNCR2820690320>3.0.CO;2-C
[48]
Abhyankar, S., Chiang, K., McGuirk, J., Pati, A., Godder, K., Welsh, J., et al. (1998) Late Onset Epstein-Barr Virus-Associated Lymphoproliferative Disease after Allogeneic Bone Marrow Transplant Presenting as Breast Masses. Bone Marrow Transplantation, 21, 295-297. https://doi.org/10.1038/sj.bmt.1701070
[49]
Kleer, C.G., Tseng, M.D., Gutsch, D.E., Rochford, R.A., Wu, Z., Joynt, L.K., et al. (2002) Detection of Epstein-Barr Virus in Rapidly Growing Fibroadenomas of the Breast in Immunosuppressed Hosts. Modern Pathology, 15, 759-764. https://doi.org/10.1038/modpathol.3880602
[50]
Speck, P. and Longnecker, R. (2000) Infection of Breast Epithelial Cells with Epstein-Barr Virus via Cell-to-Cell Contact. Journal of the National Cancer Institute, 92, 1849-1851. https://doi.org/10.1093/jnci/92.22.1849
[51]
Horiuchi, K., Mishima, K., Ohsawa, M. and Aozasa, K. (1994) Carcinoma of Stomach and Breast with Lymphoid Stroma: Localisation of Epstein-Barr Virus. Journal of Clinical Pathology, 47, 538-540. https://doi.org/10.1136/jcp.47.6.538
[52]
Brink, A.A., van den Brule, A.J., van Diest, P. and Meijer, C.J. (2000) Re: Detection of Epstein-Barr Virus in Invasive Breast Cancers. Journal of the National Cancer Institute, 92, 655-656. https://doi.org/10.1093/jnci/92.8.655
[53]
Grinstein, S., Preciado, M.V., Gattuso, P., Chabay, P.A., Warren, W.H., De Matteo, E., et al. (2002) Demonstration of Epstein-Barr Virus in Carcinomas of Various Sites. Cancer Research, 62, 4876-4878.
[54]
Preciado, M.V. (2003) Lack of Evidence for an Association of Epstein-Barr Virus Infection with Breast Carcinoma—Another Point of View. Breast Cancer Research, 5, E6. https://doi.org/10.1186/bcr599
[55]
Lorenzetti, M.A., De Matteo, E., Gass, H., Vazquez, P.M., Lara, J., Gonzalez, P., et al. (2010) Characterization of Epstein Barr virus Latency Pattern in Argentine Breast Carcinoma. PLoS One, 5, e13603. https://doi.org/10.1371/journal.pone.0013603
[56]
Gaffey, M., Frierson Jr., H., Mills, S., Boyd, J., Zarbo, R., Simpson, J., et al. (1993) Medullary Carcinoma of the Breast. Identification of Lymphocyte Subpopulations and Their Significance. Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, 6, 721-728.
[57]
Lespagnard, L., Cochaux, P., Larsimont, D., Degeyter, M., Velu, T. and Heimann, R. (1995) Absence of Epstein-Barr Virus in Medullary Carcinoma of the Breast as Demonstrated by Immunophenotyping, In Situ Hybridization and Polymerase Chain Reaction. American Journal of Clinical Pathology, 103, 449-452. https://doi.org/10.1093/ajcp/103.4.449
[58]
Dadmanesh, F., Peterse, J., Sapino, A., Fonelli, A. and Eusebi, V. (2001) Lymphoepithelioma-Like Carcinoma of the Breast: Lack of Evidence of Epstein-Barr Virus Infection. Histopathology, 38, 54-61. https://doi.org/10.1046/j.1365-2559.2001.01055.x
[59]
Kijima, Y., Hokita, S., Takao, S., Baba, M., Natsugoe, S., Yoshinaka, H., et al. (2001) Epstein-Barr Virus Involvement Is Mainly Restricted to Lymphoepithelial Type of Gastric Carcinoma among Various Epithelial Neoplasms. Journal of Medical Virology, 64, 513-518. https://doi.org/10.1002/jmv.1079
[60]
Glaser, S.L., Hsu, J.L. and Gulley, M.L. (2004) Epstein-Barr Virus and Breast Cancer: State of the Evidence for Viral Carcinogenesis. Cancer Epidemiology and Prevention Biomarkers, 13, 688-697.
[61]
Mant, C., Hodgson, S., Hobday, R., D’Arrigo, C. and Cason, J. (2004) A Viral Aetiology for Breast Cancer: Time to Re-Examine the Postulate. Intervirology, 47, 2-13. https://doi.org/10.1159/000076636
[62]
Chu, P.G., Chang, K.L., Chen, Y.-Y., Chen, W.-G. and Weiss, L.M. (2001) No Significant Association of Epstein-Barr Virus Infection with Invasive Breast Carcinoma. The American Journal of Pathology, 159, 571-578. https://doi.org/10.1016/S0002-9440(10)61728-2
[63]
Al-Alwany, S. and Ali, S. (2013) Molecular Detection of Human Cytomegalovirus in Iraqi Patients with Breast Cancer. IJABR, 3, 454-459.
[64]
Utrera-Barillas, D., Valdez-Salazar, H.-A., Gómez-Rangel, D., Alvarado-Cabrero, I., Aguilera, P., Gómez-Delgado, A., et al. (2013) Is Human Cytomegalovirus Associated with Breast Cancer Progression? Infectious Agents and Cancer, 8, 12. https://doi.org/10.1186/1750-9378-8-12
[65]
Lee, S. and Schmitt, C.A. (2003) Chemotherapy Response and Resistance. Current Opinion in Genetics & Development, 13, 90-96. https://doi.org/10.1016/S0959-437X(02)00014-X
[66]
Michaelis, M., Doerr, H.W. and Cinatl, J. (2009) Oncomodulation by Human Cytomegalovirus: Evidence Becomes Stronger. Medical Microbiology and Immunology, 198, 79-81. https://doi.org/10.1007/s00430-009-0107-8
[67]
Powers, C., DeFilippis, V., Malouli, D. and Frueh, K. (2008) Cytomegalovirus Immune Evasion. Human Cytomegalovirus: Springer, 333-359. https://doi.org/10.1007/978-3-540-77349-8_19
[68]
Hirano, T. (1998) Interleukin 6 and Its Receptor: Ten Years Later. International Reviews of Immunology, 16, 249-284. https://doi.org/10.3109/08830189809042997
[69]
Deroo, B.J. and Korach, K.S. (2006) Estrogen Receptors and Human Disease. The Journal of Clinical Investigation, 116, 561-570. https://doi.org/10.1172/JCI27987
