Skip to main content

Advertisement

Log in

Breast cancer and cytomegalovirus

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Purpose

To determine whether cytomegalovirus is causally associated with breast cancer and whether cytomegalovirus should be categorised as an oncogenic virus.

Methods

We undertook a review of published epidemiological and laboratory studies, using established causal criteria: Bradford Hill criteria to determine whether cytomegalovirus is associated with breast cancer; and Evans/Mueller criteria to determine whether cytomegalovirus should be categorised as an oncogenic virus.

Results

Although there are inconsistencies in the findings of published epidemiological and laboratory studies, these may be explained by factors such as: differences in timing of blood samples, differences in selection of cases and controls, or high cytomegalovirus seroprevalence among participants in the epidemiological studies; and, in the laboratory studies, differences in sample preparations, age of sample, whether or not paired breast cancer and normal breast tissue samples were used, differences in the tests, primers and/or antibodies used, differences in histological types of breast cancer studied, and/or features of the virus.

Conclusions

Overall, the results of published studies of cytomegalovirus and breast cancer suggest cytomegalovirus is a causal factor for at least some types of breast cancer. If the evidence for a link between cytomegalovirus and breast cancer continues to strengthen, further research could lead to: targeted screening; therapy using antiviral drugs; and, perhaps, primary prevention of a significant proportion of breast cancer. Vaccination against viruses has already been shown to be effective in preventing cervix and liver cancer; cytomegalovirus vaccines are already under development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Hill AB. The environment and disease: association or causation?. Thousand Oaks: SAGE Publications; 1965.

    Google Scholar 

  2. Evans AS, Mueller NE. Viruses and cancer causal associations. Ann Epidemiol. 1990;1(1):71–92.

    CAS  PubMed  Google Scholar 

  3. Plummer M, de Martel C, Vignat J, Ferlay J, Bray F, Franceschi S. Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Global Health. 2016;4(9):e609–e616616.

    PubMed  Google Scholar 

  4. Global Burden of Disease Cancer Collaboration. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol. 2017;3(4):524.

    PubMed Central  Google Scholar 

  5. Hoover RN. That recognised risk factors can explain past and present international differences in breast cancer incidence: misconceptions 5. Br J Cancer. 2012;107(3):408–10. https://doi.org/10.1038/bjc.2012.134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. MacMahon B. Epidemiology and the causes of breast cancer. Int J Cancer. 2006;118(10):2373–8. https://doi.org/10.1002/ijc.21404.

    Article  CAS  PubMed  Google Scholar 

  7. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.

    Article  PubMed  Google Scholar 

  8. Thomas DB. Breast cancer in men. Epidemiol Rev. 1993;15(1):220–31.

    CAS  PubMed  Google Scholar 

  9. Ewertz M, Holmberg L, Karjalainen S, Tretli S, Adami HO. Incidence of male breast cancer in Scandinavia, 1943–1982. Int J Cancer. 1989;43(1):27–31.

    CAS  PubMed  Google Scholar 

  10. Ly D, Forman D, Ferlay J, Brinton LA, Cook MB. An international comparison of male and female breast cancer incidence rates. Int J Cancer. 2013;132(8):1918–26. https://doi.org/10.1002/ijc.27841.

    Article  CAS  PubMed  Google Scholar 

  11. Kreiter E, Richardson A, Potter J, Yasui Y. Breast cancer: trends in international incidence in men and women. Br J Cancer. 2014;110(7):1891–7. https://doi.org/10.1038/bjc.2014.66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Andreeva VA, Unger JB, Pentz MA. Breast cancer among immigrants: a systematic review and new research directions. J Immigr Minor Health. 2007;9(4):307–22. https://doi.org/10.1007/s10903-007-9037-y.

    Article  PubMed  Google Scholar 

  13. Anderson WF, Jatoi I, Tse J, Rosenberg PS. Male breast cancer: a population-based comparison with female breast cancer. J Clin Oncol. 2010;28(2):232–9. https://doi.org/10.1200/JCO.2009.23.8162.

    Article  PubMed  Google Scholar 

  14. Ylitalo N, Stuver S, Adami HO. Cervical cancer. In: Adami HO, Hunter D, Trichopoulos D, editors. Textbook of cancer epidemiology. Oxford: Oxford University Press; 2008.

    Google Scholar 

  15. Castellsague X. Natural history and epidemiology of HPV infection and cervical cancer. Gynecol Oncol. 2008;110(3 Suppl 2):S4–7. https://doi.org/10.1016/j.ygyno.2008.07.045.

    Article  PubMed  Google Scholar 

  16. Mocarski ES, Shenk T, Griffiths PD, Pass RF. Cytomegaloviruses. In: Knipe DM, Howley PM, editors. Fields virology. vol. 2, 6th edn. Philadelphia: Lippincott Williams and Wilkins; 2013. pp. 1960–2014.

  17. Ludwig A, Hengel H. Epidemiological impact and disease burden of congenital cytomegalovirus infection in Europe. Euro Surveill. 2009;14(9):26–322.

    CAS  PubMed  Google Scholar 

  18. Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol. 2010;20(4):202–13. https://doi.org/10.1002/rmv.655.

    Article  PubMed  Google Scholar 

  19. Hennighausen L. Mouse models for breast cancer. Breast Cancer Res. 2000;2:2–7.

    CAS  PubMed  Google Scholar 

  20. Dudley JP, Golovkina TV, Ross SR. Lessons learned from mouse mammary tumor virus in animal models. ILAR J. 2016;57(1):12–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Bonnet M, Guinebretiere JM, Kremmer E, et al. Detection of Epstein–Barr virus in invasive breast cancers. J Natl Cancer Inst. 1999;91:1376–81.

    CAS  PubMed  Google Scholar 

  22. Magrath I, Bhatia K. Breast cancer: a new Epstein–Barr virus-associated disease? J Natl Cancer Inst. 1999;91(16):1349–50.

    CAS  PubMed  Google Scholar 

  23. Fina F, Romain S, Quafik LH, et al. Frequency and genome load of Epstein–Barr virus in 509 breast cancers from different geographical areas. Br J Cancer. 2001;84:783–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Hermann K, Niedobitek G. Lack of evidence for an association of Epstein–Barr virus infection with breast carcinoma. Breast Cancer Res. 2003;5:R13–17.

    Google Scholar 

  25. Xue SA, Lampert IA, Haldane JS, Bridger JE, Griffin BE. Epstein–Barr virus gene expression in human breast cancer: protagonist or passenger? Br J Cancer. 2003;89(1):113–9. https://doi.org/10.1038/sj.bjc.6601027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. He JR, Tang LY, Yu DD, Su FX, Song EW, Lin Y, Wang SM, Lai GC, Chen WQ, Ren ZF. Epstein–Barr virus and breast cancer: serological study in a high-incidence area of nasopharyngeal carcinoma. Cancer Lett. 2011;309(2):128–36. https://doi.org/10.1016/j.canlet.2011.05.012.

    Article  CAS  PubMed  Google Scholar 

  27. Mazouni C, Fina F, Romain S, Ouafik L, Bonnier P, Brandone JM, Martin PM. Epstein–Barr virus as a marker of biological aggressiveness in breast cancer. Br J Cancer. 2011;104(2):332–7. https://doi.org/10.1038/sj.bjc.6606048.

    Article  CAS  PubMed  Google Scholar 

  28. Perkins RS, Sahm K, Marando C, Dickson-Witmer D, Pahnke GR, Mitchell M, Petrelli NJ, Berkowitz IM, Soteropoulos P, Aris VM, Dunn SP, Krueger LJ. Analysis of Epstein–Barr virus reservoirs in paired blood and breast cancer primary biopsy specimens by real time PCR. Breast Cancer Res. 2006;8(6):R70. https://doi.org/10.1186/bcr1627.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Perrigoue JG, den Boon JA, Friedl A, Newton MA, Ahlquist P, Sugden B. Lack of association between EBV and breast carcinoma. Cancer Epidemiol Biomark Prev. 2005;14(4):809–14. https://doi.org/10.1158/1055-9965.EPI-04-0763.

    Article  CAS  Google Scholar 

  30. Khan G, Philip PS, Al Ashari M, Houcinat Y, Daoud S. Localization of Epstein–Barr virus to infiltrating lymphocytes in breast carcinomas and not malignant cells. Exp Mol Pathol. 2011;91(1):466–70. https://doi.org/10.1016/j.yexmp.2011.04.018.

    Article  CAS  PubMed  Google Scholar 

  31. Agborsangaya CB, Lehtinen T, Toriola AT, Pukkala E, Surcel HM, Tedeschi R, Lehtinen M. Association between Epstein–Barr virus infection and risk for development of pregnancy-associated breast cancer: Joint effect with vitamin D? Eur J Cancer. 2011;47(1):116–20.

    CAS  PubMed  Google Scholar 

  32. Glaser SL, Hsu JL, Gulley ML. Epstein–Barr virus and breast cancer: state of the evidence for viral carcinogenesis. Cancer Epidemiol Biomark Prev. 2004;13(5):688–97.

    CAS  Google Scholar 

  33. Mant C, Cason J. A human murine mammary tumour virus-like agent is an unconvincing aetiological agent for human breast cancer. Rev Med Virol. 2004;14(3):169–77. https://doi.org/10.1002/rmv.427.

    Article  CAS  PubMed  Google Scholar 

  34. Szabo S, Haislip AM, Garry RF. Of mice, cats, and men: is human breast cancer a zoonosis? Microsc Res Tech. 2005;68(3–4):197–208. https://doi.org/10.1002/jemt.20232.

    Article  CAS  PubMed  Google Scholar 

  35. Richardson AK, Currie MJ, Robinson BA, Morrin H, Phung Y, Pearson JF, Anderson TP, Potter JD, Walker LC. Cytomegalovirus and Epstein–Barr virus in breast cancer. PLoS ONE. 2015;10(2):e0118989. https://doi.org/10.1371/journal.pone.0118989.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Michaelis M, Doerr HW, Cinatl J. The story of human cytomegalovirus and cancer: increasing evidence and open questions. Neoplasia. 2009;11(1):1–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Herbein G. The human cytomegalovirus, from oncomodulation to oncogenesis. Viruses. 2018;10(8):408.

    PubMed Central  Google Scholar 

  38. Michaelis M, Baumgarten P, Mittelbronn M, Driever PH, Doerr HW, Cinatl J Jr. Oncomodulation by human cytomegalovirus: novel clinical findings open new roads. Med Microbiol Immunol. 2011;200(1):1–5.

    PubMed  Google Scholar 

  39. Soderberg-Naucler C. Treatment of cytomegalovirus infections beyond acute disease to improve human health. Expert Rev Anti Infect Ther. 2014;12(2):211–22. https://doi.org/10.1586/14787210.2014.870472.

    Article  CAS  PubMed  Google Scholar 

  40. Soroceanu L, Cobbs CS. Is HCMV a tumor promoter? Virus Res. 2011;157:193–203.

    CAS  PubMed  Google Scholar 

  41. Pandey JP. Immunoglobulin GM genes, cytomegalovirus immunoevasion, and the risk of glioma, neuroblastoma, and breast cancer. Front Oncol. 2014;4:236. https://doi.org/10.3389/fonc.2014.00236.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Richardson A. Is breast cancer caused by late exposure to a common virus? Med Hypotheses. 1997;48(6):491–7.

    CAS  PubMed  Google Scholar 

  43. Kumar A, Tripathy MK, Pasquereau S, Al Moussawi F, Abbas W, Coquard L, Khan KA, Russo L, Algros MP, Valmary-Degano S, Adotevi O, Morot-Bizot S, Herbein G. The human cytomegalovirus strain DB activates oncogenic pathways in mammary epithelial cells. EBioMedicine. 2018;30:167–83. https://doi.org/10.1016/j.ebiom.2018.03.015.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Rahbar A, Touma J, Costa H, Davoudi B, Bukholm IR, Sauer T, Vetvik K, Geisler J, Soderberg-Naucler C. Low expression of estrogen receptor-alpha and progesterone receptor in human breast cancer tissues is associated with high-grade human cytomegalovirus protein expression. Clin Breast Cancer. 2017;17(7):526–535.e521. https://doi.org/10.1016/j.clbc.2017.04.013.

    Article  CAS  PubMed  Google Scholar 

  45. Cui J, Wang Q, Wang HB, Wang B, Li L. Protein and DNA evidences of HCMV infection in primary breast cancer tissues and metastatic sentinel lymph nodes. Cancer Biomark Sect A Dis Mark. 2018;21(4):769–80. https://doi.org/10.3233/CBM-170409.

    Article  CAS  Google Scholar 

  46. Al Moussawi F, Kumar A, Pasquereau S, Tripathy MK, Karam W, Diab-Assaf M, Herbein G. The transcriptome of human mammary epithelial cells infected with the HCMV-DB strain displays oncogenic traits. Sci Rep. 2018. https://doi.org/10.1038/s41598-018-30109-1.

    Article  Google Scholar 

  47. Puchhammer-Stöckl E, Görzer I. Human cytomegalovirus: an enormous variety of strains and their possible clinical significance in the human host. Future Virol. 2011;6(2):259–71.

    Google Scholar 

  48. Sijmons S, Van Ranst M, Maes P. Genomic and functional characteristics of human cytomegalovirus revealed by next-generation sequencing. Viruses. 2014;6(3):1049–72.

    PubMed  PubMed Central  Google Scholar 

  49. Moore PS, Chang Y. Why do viruses cause cancer? Highlights of the first century of human tumour virology. Nat Rev Cancer. 2010;10(12):878–89. https://doi.org/10.1038/nrc2961.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Pagano JS, Blaser M, Buendia M-A, Damania B, Khalili K, Raab-Traub N, Roizman B. Infectious agents and cancer: criteria for a causal relation. In: Seminars in cancer biology. vol. 6. Amsterdam: Elsevier; 2004. pp. 453–471.

    CAS  PubMed  Google Scholar 

  51. Niller HH, Wolf H, Minarovits J. Viral hit and run-oncogenesis: genetic and epigenetic scenarios. Cancer Lett. 2011;305(2):200–17. https://doi.org/10.1016/j.canlet.2010.08.007.

    Article  CAS  PubMed  Google Scholar 

  52. Alibek K, Kakpenova A, Mussabekova A, Sypabekova M, Karatayeva N. Role of viruses in the development of breast cancer. Infect Agent Cancer. 2013;8(1):32. https://doi.org/10.1186/1750-9378-8-32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Hamidullah Changkija B, Konwar R. Role of interleukin-10 in breast cancer. Breast Cancer Res Treat. 2012;133(1):11–21. https://doi.org/10.1007/s10549-011-1855-x.

    Article  CAS  PubMed  Google Scholar 

  54. Liao H, Tsai CH. Data mining for DNA viruses with breast cancer, fibroadenoma, and normal mammary tissue. Appl Math Comput. 2007;188:989–1000.

    Google Scholar 

  55. Hsu CR, Lu TM, Chin LW, Yang CC. Possible DNA viral factors of human breast cancer. Cancers (Basel). 2010;2(2):498–512. https://doi.org/10.3390/cancers2020498.

    Article  CAS  Google Scholar 

  56. El-Shinawi M, Mohamed HT, Abdel-Fattah HH, Ibrahim SA, El-Halawany MS, Nouh MA, Schneider RJ, Mohamed MM. Inflammatory and non-inflammatory breast cancer: a potential role for detection of multiple viral DNAs in disease progression. Ann Surg Oncol. 2016;23(2):494–502. https://doi.org/10.1245/s10434-015-4888-2.

    Article  PubMed  Google Scholar 

  57. Tsai JH, Tsai CH, Cheng MH, Lin SJ, Xu FL, Yang CC. Association of viral factors with non-familial breast cancer in Taiwan by comparison with non-cancerous, fibroadenoma, and thyroid tumor tissues. J Med Virol. 2005;75(2):276–81. https://doi.org/10.1002/jmv.20267.

    Article  PubMed  Google Scholar 

  58. Tsai J, Hsu C, Tsai C, et al. Relationship between viral factors, axillary lymph node status and survival in breast cancer. J Cancer Res Clin Ocol. 2007;133:13–211.

    Google Scholar 

  59. Soderberg-Naucler C. HCMV microinfections in inflammatory diseases and cancer. J Clin Virol. 2008;41(3):218–23. https://doi.org/10.1016/j.jcv.2007.11.009.

    Article  CAS  PubMed  Google Scholar 

  60. Baryawno N, Rahbar A, Wolmer-Solberg N, et al. Detection of human cytomegalovirus in medulloblastomas reveals a potential therapeutic target. J Clin Investig. 2011. https://doi.org/10.1172/JCI57147.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Straat K, Liu C, Rahbar A, Zhu Q, Liu L, Wolmer-Solberg N, Lou F, Liu Z, Shen J, Jia J, Kyo S, Bjorkholm M, Sjoberg J, Soderberg-Naucler C, Xu D. Activation of telomerase by human cytomegalovirus. J Natl Cancer Inst. 2009;101(7):488–97. https://doi.org/10.1093/jnci/djp031.

    Article  CAS  PubMed  Google Scholar 

  62. Pandey JP, Kistner-Griffin E, Iwasaki M, Bu S, Deepe R, Black L, Kasuga Y, Hamada GS, Tsugane S. Genetic markers of immunoglobulin G and susceptibility to breast cancer. Hum Immunol. 2012;73(11):1155–8. https://doi.org/10.1016/j.humimm.2012.07.340.

    Article  CAS  PubMed  Google Scholar 

  63. Pasquereau S, Al Moussawi F, Karam W, Diab Assaf M, Kumar A, Herbein G. Cytomegalovirus, macrophages and breast cancer. Open Virol J. 2017;11:15–27. https://doi.org/10.2174/1874357901711010015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Mohammadizadeh F, Mahmudi F. Evaluation of human cytomegalovirus antigen expression in invasive breast carcinoma in a population of Iranian patients. Infect Agents Cancer (Electronic Resource). 2017;12:39. https://doi.org/10.1186/s13027-017-0148-3.

    Article  CAS  Google Scholar 

  65. Paulus C, Nevels M. The human cytomegalovirus major immediate-early proteins as antagonists of intrinsic and innate antiviral host responses. Viruses. 2009;1(3):760–79.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Ranneberg-Nilsen T, Bjørås M, Luna L, Slettebakk R, Dale HA, Seeberg E, Rollag H. Human cytomegalovirus infection modulates DNA base excision repair in fibroblast cells. Virology. 2006;348(2):389–97.

    CAS  PubMed  Google Scholar 

  67. Antonsson A, Bialasiewicz S, Rockett RJ, Jacob K, Bennett IC, Sloots TP. Exploring the prevalence of ten polyomaviruses and two herpes viruses in breast cancer. PLoS ONE. 2012;7(8):e39842. https://doi.org/10.1371/journal.pone.0039842.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Stinski MF, Isomura H. Role of the cytomegalovirus major immediate early enhancer in acute infection and reactivation from latency. Med Microbiol Immunol. 2008;197(2):223–31.

    PubMed  Google Scholar 

  69. Elenbaas B, Spirio L, Koerner F, Fleming MD, Zimonjic DB, Donaher JL, Popescu NC, Hahn WC, Weinberg RA. Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells. Genes Dev. 2001;15(1):50–655.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Chung SS, Aroh C, Vadgama JV. Constitutive activation of STAT3 signaling regulates hTERT and promotes stem cell-like traits in human breast cancer cells. PLoS ONE. 2013;8(12):e83971.

    PubMed  PubMed Central  Google Scholar 

  71. Cox B, Richardson A, Graham P, Gislefoss RE, Jellum E, Rollag H. Breast cancer, cytomegalovirus and Epstein–Barr virus: a nested case–control study. Br J Cancer. 2010;102:1665–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Bosch FX, de Sanjosé S. The epidemiology of human papillomavirus infection and cervical cancer. Dis Markers. 2007;23(4):213–27.

    PubMed  PubMed Central  Google Scholar 

  73. Surendran A, Chisthi MMJJOIS. Breast cancer association with cytomegalo virus—a tertiary center case–control study. J Investig Surg. 2017;32(2):1–6. https://doi.org/10.1080/08941939.2017.1397827.

    Article  Google Scholar 

  74. Akhter J, Ali Aziz MA, Al Ajlan A, Tulbah A, Akhtar M. Breast cancer: is there a viral connection? Adv Anat Pathol. 2014;21(5):373–81. https://doi.org/10.1097/PAP.0000000000000037.

    Article  PubMed  Google Scholar 

  75. Guyard A, Boyez A, Pujals A, Robe C, Van Nhieu JT, Allory Y, Moroch J, Georges O, Fournet J-C, Zafrani E-S. DNA degrades during storage in formalin-fixed and paraffin-embedded tissue blocks. Virchows Arch. 2017;471(4):491–500.

    CAS  PubMed  Google Scholar 

  76. Richardson AK, Cox B, McCredie MR, Dite GS, Chang JH, Gertig DM, Southey MC, Giles GG, Hopper JL. Cytomegalovirus, Epstein–Barr virus and risk of breast cancer before age 40 years: a case–control study. Br J Cancer. 2004;90(11):2149–52. https://doi.org/10.1038/sj.bjc.6601822.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Alsamarai A, Abdulla S, Khalifa Z. Role of cytomegalovirus and Epstein–Barr virus in breast cancer. WJPPS. 2015;4(11):115–42.

    CAS  Google Scholar 

  78. Ahmed RA, Yussif SM. Immunohistochemical detection of human cytomegalovirus, Epstein–Barr virus and human papillomavirus in invasive breast carcinoma in Egyptian women: a tissue microarray study. J Solid Tumors. 2016;6(2):8–16. https://doi.org/10.5430/jst.v6n2p8.

    Article  Google Scholar 

  79. Sullivan T, Ashbury FD, Fallone CA, Naja F, Schabas R, Hébert PC, Hunt R, Jones N. Helicobacter pylori and the prevention of gastric cancer. Can J Gastroenterol Hepatol. 2004;18(5):295–302.

    Google Scholar 

  80. Eslick GD. Helicobacter pylori infection causes gastric cancer A? review of the epidemiological, meta-analytic, and experimental evidence. World J Gastroenterol WJG. 2006;12(19):2991.

    PubMed  Google Scholar 

  81. Bosch FX, Lorincz A, Muñoz N, Meijer C, Shah KV. The causal relation between human papillomavirus and cervical cancer. J Clin Pathol. 2002;55(4):244–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Liou JM, Lee YC, El-Omar EM, Wu MS. Efficacy and long-term safety of H. pylori eradication for gastric cancer prevention. Cancers (Basel). 2019;11(5):593. https://doi.org/10.3390/cancers11050593.

    Article  CAS  Google Scholar 

  83. Rothman KJ, Greenland S. Causation and causal inference in epidemiology. Am J Public Health. 2005;95(S1):S144–S150150.

    PubMed  Google Scholar 

  84. Pandey JP, Gao G, Namboodiri AM, Iwasaki M, Kasuga Y, Hamada GS, Tsugane S. Humoral immunity to cytomegalovirus glycoprotein B in patients with breast cancer and matched controls: contribution of immunoglobulin gamma, kappa, and Fcgamma receptor genes. J Infect Dis. 2016;213(4):611–7. https://doi.org/10.1093/infdis/jiv472.

    Article  CAS  PubMed  Google Scholar 

  85. Yasui Y, Potter JD, Stanford JL, Rossing MA, Winget MD, Bronner M, Daling J. Breast cancer risk and "delayed" primary Epstein–Barr virus infection. Cancer Epidemiol Biomark Prev. 2001;10(1):9–16.

    CAS  Google Scholar 

  86. Harkins LE, Matalaf LA, Soroceanu L, et al. Detection of human cytomegalovirus in normal and neoplastic breast epithelium. Herpesviridae. 2010;1(1):8. https://doi.org/10.1186/2042-4280-1-8.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Eghbali M, Ghane M, Mirinargesi M. Frequency of cytomegalovirus (CMV) in benign and malignant tumors. Int J Mol Clin Microbiol. 2012;2:175–9.

    Google Scholar 

  88. Taher C, de Boniface J, Mohammad AA, Religa P, Hartman J, Yaiw KC, Frisell J, Rahbar A, Soderberg-Naucler C. High prevalence of human cytomegalovirus proteins and nucleic acids in primary breast cancer and metastatic sentinel lymph nodes. PLoS ONE. 2013;8(2):e56795. https://doi.org/10.1371/journal.pone.0056795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Mohammed AH, Kadhim HS, Ghani AH. Investigation the role of human cytomegalovirus in the invasive ductal breast carcinoma. Clin Cancer Investig J. 2015;4(2):199–205. https://doi.org/10.4103/2278-0513.148915.

    Article  Google Scholar 

  90. El Shazly DF, Bahnassey AA, Omar OS, Elsayed ET, Al-Hindawi A, El-Desouky E, Youssef H, Zekri AN. Detection of human cytomegalovirus in malignant and benign breast tumors in Egyptian women. Clin Breast Cancer. 2018;18(4):e629–e642642. https://doi.org/10.1016/j.clbc.2017.10.018.

    Article  PubMed  Google Scholar 

  91. Bakhtiyrizadeh S, Hosseini SY, Yaghobi R, Safaei A, Sarvari J. Almost complete lack of human cytomegalovirus and human papillomaviruses genome in benign and malignant breast lesions in Shiraz, Southwest of Iran. Asian Pac J Cancer Prev. 2017;18(12):3319–24.

    PubMed  PubMed Central  Google Scholar 

  92. Kane MA. Preventing cancer with vaccines: progress in the global control of cancer. Cancer Prev Res. 2012;5(1):24–9.

    Google Scholar 

  93. Schleiss MR. Cytomegalovirus vaccines under clinical development. J Virus Erad. 2016;2(4):198.

    PubMed  PubMed Central  Google Scholar 

  94. Pandey JP. Genetic markers of immunoglobulin G as potential risk factors for IgG4-related disease. J Rheumatol. 2012;39(10):2048. https://doi.org/10.3899/jrheum.120671.

    Article  PubMed  Google Scholar 

  95. Aljumaili ZKM, Alsamarai AM, Najem WS. Cytomegalovirus seroprevalence in women with bad obstetric history in Kirkuk, Iraq. J Infect Public Health. 2014;7(4):277–88.

    PubMed  Google Scholar 

  96. Pandey JP, Namboodiri AM, Mohan S, Nietert PJ, Peterson L. Genetic markers of immunoglobulin G and immunity to cytomegalovirus in patients with breast cancer. Cell Immunol. 2017;312:67–70. https://doi.org/10.1016/j.cellimm.2016.11.003.

    Article  CAS  PubMed  Google Scholar 

  97. El-Shinawi M, Mohamed HT, El-Ghonaimy EA, Tantawy M, Younis A, Schneider RJ, Mohamed MM. Human cytomegalovirus infection enhances NF-kappaB/p65 signaling in inflammatory breast cancer patients. PLoS ONE. 2013;8(2):e55755. https://doi.org/10.1371/journal.pone.0055755.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Utrera-Barillas D, Valdez-Salazar HA, Gomez-Rangel D, Alvarado-Cabrero I, Aguilera P, Gomez-Delgado A, Ruiz-Tachiquin ME. Is human cytomegalovirus associated with breast cancer progression? Infect Agents Cancer (Electronic Resource). 2013;8(1):12. https://doi.org/10.1186/1750-9378-8-12.

    Article  CAS  Google Scholar 

  99. De Paschale M, Agrappi C, Manco MT, Clerici P. Positive predictive value of anti-HCMV IgM as an index of primary infection. J Virol Methods. 2010;168(1–2):121–5.

    PubMed  Google Scholar 

  100. Holdhoff M, Guner G, Rodriguez FJ, Hicks JL, Zheng Q, Forman MS, Ye X, Grossman SA, Meeker AK, Heaphy CM. Absence of cytomegalovirus in glioblastoma and other high-grade gliomas by real-time PCR, immunohistochemistry, and in situ hybridization. Clin Cancer Res. 2017;23(12):3150–7.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Ann Richardson is partially supported by the Wayne Francis Charitable Trust. Brian Cox is partially supported by the Director’s Cancer Research Trust administered by Perpetual Guardian, New Zealand. Bridget Robinson is partially supported by the Mackenzie Charitable Foundation. Margaret Currie is partially supported by the Mackenzie Charitable Foundation. Logan Walker is supported by a Royal Society of New Zealand Rutherford Discovery Fellowship

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. K. Richardson.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

The manuscript does not contain clinical studies or patient data.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Richardson, A.K., Walker, L.C., Cox, B. et al. Breast cancer and cytomegalovirus. Clin Transl Oncol 22, 585–602 (2020). https://doi.org/10.1007/s12094-019-02164-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-019-02164-1

Keywords

Navigation