Epstein–Barr virus gene expression in human breast cancer: protagonist or passenger?

Xue, Shao-An; Lampert, Irvin A.; Haldane, J. S.; Bridger, J. E.; Griffin, Beverly E.

doi:10.1038/sj.bjc.6601027

Cited by 60 publications

(51 citation statements)

References 47 publications

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“…The hypothesis has also been investigated by examining birth cohort trends in the incidence of breast cancer and Hodgkin's disease (Krieger et al, 2003). Several studies have investigated EpsteinBarr virus gene expression in human breast cancer, with inconsistent results (Bonnet et al, 1999;Magrath and Bhatia, 1999;Fina et al, 2001;Hermann and Niedobitek, 2003;Xue et al, 2003). Our study is the only one we know of to investigate breast cancer and EBV or CMV using blood samples and serological testing.…”

Section: Discussionmentioning

confidence: 98%

Cytomegalovirus, Epstein–Barr virus and risk of breast cancer before age 40 years: a case–control study

et al. 2004

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We investigated whether there is an association between cytomegalovirus (CMV) and Epstein -Barr virus (EBV) IgG levels and risk of breast cancer before age 40 years. CMV and EBV IgG levels were measured in stored plasma from 208 women with breast cancer and 169 controls who participated in the Australian Breast Cancer Family Study (ABCFS), a population-based case -control study. CMV and EBV IgG values were measured in units of optical density (OD). Cases and controls did not differ in seropositivity for CMV (59 and 57% respectively; P ¼ 0.8) or EBV (97 and 96% respectively; P ¼ 0.7). In seropositive women, mean IgG values were higher in cases than controls for CMV (1.20 vs 0.98 OD, P ¼ 0.005) but not for EBV (2.65 vs 2.57 OD, P ¼ 0.5). The adjusted odds ratios per OD unit were 1.46 (95% CI 1.06 -2.03) for CMV IgG and 1.11 (0.93 -1.33) for EBV IgG. The higher mean CMV IgG levels found in women with breast cancer could be the result of a more recent infection with CMV, and may mean that late exposure to CMV is a risk factor for breast cancer.

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Section: Discussionmentioning

confidence: 98%

Cytomegalovirus, Epstein–Barr virus and risk of breast cancer before age 40 years: a case–control study

et al. 2004

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“…Xue et al (41) detected EBV transcripts in samples sorted for the absence of lymphocytes. They detected EBNA-1 and BARF-1 RNA in three of six cases.…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus (EBV) Genome and Expression in Breast Cancer Tissue: Effect of EBV Infection of Breast Cancer Cells on Resistance to Paclitaxel (Taxol)

Arbach

Víglaský

Lefeu

et al. 2006

J Virol

103

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The Epstein-Barr virus (EBV) has been detected in subsets of breast cancers. In order to elaborate on these observations, we quantified by real-time PCR (Q-PCR) the EBV genome in biopsy specimens of breast cancer tissue as well as in tumor cells isolated by microdissection. Our findings show that EBV genomes can be detected by Q-PCR in about half of tumor specimens, usually in low copy numbers. However, we also found that the viral load is highly variable from tumor to tumor. Moreover, EBV genomes are heterogeneously distributed in morphologically identical tumor cells, with some clusters of isolated tumor cells containing relatively high genome numbers while other tumor cells isolated from the same specimen may be negative for EBV DNA. Using reverse transcription-PCR, we detected EBV gene transcripts: EBNA-1 in almost all of the EBV-positive tumors and RNA of the EBV oncoprotein LMP-1 in a smaller subset of the tissues analyzed. Moreover, BARF-1 RNA was detected in half of the cases studied. Furthermore, we observed that in vitro EBV infection of breast carcinoma cells confers resistance to paclitaxel (taxol) and provokes overexpression of a multidrug resistance gene (MDR1). Consequently, even if a small number of breast cancer cells are EBV infected, the impact of EBV infection on the efficiency of anticancer treatment might be of importance.The Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, is associated with the development of different epithelial malignancies (28), including nasopharyngeal carcinoma (NPC). It has also been linked with subsets of other types of carcinomas, including gastric carcinoma and lymphoepithelioma-like carcinoma in salivary glands and thymus (32,44). Several laboratories have reported detection of EBV in a subset of breast tumors (3,10,19,23). However, negative results have also been reported (6,9,14,27). Nevertheless, in most of the studies, a low viral load was detected in breast cancer biopsy specimens but the infected cells were not clearly identified. In the study presented here, we used real-time PCR (Q-PCR) to quantify the copy numbers of the EBV genome in biopsy specimens as well as in microdissected tumor cells. The results show that breast cancer cells harbor the viral genome. However, through microdissection and isolation of pure tumor cells, we now find that even in EBV-positive tumor samples, many tumor cells do not contain EBV genomes and that the breast carcinomas are highly heterogeneous in terms of genome content and distribution. Moreover, using reverse transcription-PCR (RT-PCR), we detected EBNA-1 and BARF-1 transcripts in almost all of the EBV-positive tumors and LMP-1 RNA in 3 of the 15 cases studied. The findings raise the possibility that although EBV is unlikely to have an etiologic role in the genesis of breast cancer, the virus might contribute to tumor progression. Finally, the potential impact of EBV in breast cancer progression was evaluated by estimation of resistance to chemotherapeutic agents on in vitro-infected MDA-MB-231 cells. The resul...

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“…This is particularly the case since as an uncommon response to a nonsexually transmitted agent, there would be nothing obviously to suggest infection. Over the past decade, laboratory reports offering somewhat variable evidence of altered EBV gene expression in this disease (Labrecque et al, 1995;Magrath and Bhatia, 1999;Xue et al, 2003) have, perhaps not surprisingly, received little epidemiological attention, although an increased risk has recently been found with increasing age of selfreported infectious mononucleosis (Yasui et al, 2001).…”

Section: Breast Cancermentioning

confidence: 99%

Infections and immune factors in cancer: the role of epidemiology

Kinlen

2004

Oncogene

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An infective, mostly viral, basis has been found in an increasing number of different human cancers. In all cases, the neoplasm is a rare response to the relevant infection, which is usually present in persistent form, and requiring specific cofactors for malignancy to develop. In some cases, epidemiological evidence of infectivity preceded and promoted identification of the specific infection involved and even the discovery of the microbe itself, as in Burkitt's lymphoma and cervix cancer. In other cases, the discovery of the agent came first as in stomach and nasopharynx cancers, and epidemiology has been concerned mainly with confirming the relationship, measuring the size of the risk and identifying cofactors. Infectionlinked cancers include some of the commonest malignancies in certain large world regions, amounting to over 20% of all cancer in the developing countries. In addition to these cancers are others such as childhood leukaemia that show features indicative of an infective basis though no underlying agent has been identified. Advances in this field invite speculation about possible future discoveries and how these might be promoted. However, in that majority of cancers that are unrelated to sexual behaviour, there will be nothing even at the population level to suggest an infective basis because what is transmitted from one individual to another is not the neoplasm itself, but the underlying, often silent, infection to which the malignancy is an uncommon response. The increasing prevalence of immune impairment in human populations, as a result of the use of immunosuppressive drugs with organ transplants and the spread of HIV infection, has produced marked effects on cancer incidence in the affected groups including increases, of skin cancers, nonHodgkin's lymphoma and Kaposi's sarcoma and to a lesser extent of many other cancers, in some cases at least due to the release from immunological control of incipient infection-based malignancies.

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Epstein–Barr virus gene expression in human breast cancer: protagonist or passenger?

Cited by 60 publications

References 47 publications

Cytomegalovirus, Epstein–Barr virus and risk of breast cancer before age 40 years: a case–control study

Cytomegalovirus, Epstein–Barr virus and risk of breast cancer before age 40 years: a case–control study

Epstein-Barr Virus (EBV) Genome and Expression in Breast Cancer Tissue: Effect of EBV Infection of Breast Cancer Cells on Resistance to Paclitaxel (Taxol)

Infections and immune factors in cancer: the role of epidemiology

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