A human murine mammary tumour virus‐like agent is an unconvincing aetiological agent for human breast cancer

Abstract

There has recently been renewed interest in both the scientific literature, and in the media, that a human relative (HMLV) of murine mammary tumour virus (MMTV) may be implicated in the aetiology of up to 42% of sporadic cases of human breast cancer. Such reports are potentially of considerable clinical significance, as aside from the small percentage of genetically acquired breast cancers, the cause of sporadic cases of breast cancer is completely unknown. Indeed, convincing proof of an infectious cause for human breast malignancies would permit the development of new preventative measures, treatment modalities and raise the possibility of prophylactic and therapeutic vaccines. Here we review the historical background for a retroviral cause of human breast cancers and give an up-to-date critique of the most recent research findings. We conclude that the available evidence for an infectious aetiology of human breast cancers is unconvincing. Amongst the many cognate arguments against an infective hypothesis for sporadic cases of human breast cancer are the facts that: (i). human tissues lack the appropriate cell-surface receptor for entry of MMTVs/HMLVs; (ii). unlike all other virally caused human malignancies, immunodeficiency does not predispose to an increased incidence, or prevalence, of human breast cancers; and, (iii). reports of PCR amplification of MMTV/HMLV sequences from breast cancers have been robustly disputed by four independent laboratories. Indeed positive PCR results may be readily explained by the mis-amplification of host genomic DNA. Hence, the burden of proof currently lies with those who champion a viral cause for sporadic cases of breast cancer.

Mouse Mammary Tumor Virus–like Sequences in Human Breast Cancer

“…Mant and Cason (43) have argued that MMTV cannot have a role in human breast cancer because of the alleged histologic differences between mouse mammary tumors and human breast cancers. At low magnification MMTV-associated mouse mammary tumors do have different characteristics from human breast cancers; however, in some invasive breast cancers, the similarities can be striking in some breast cancers at a cellular level (28).…”

Breast cancer, cytomegalovirus and Epstein–Barr virus: a nested case–control study

“…Mouse mammary tumour-like viruses and Epstein -Barr virus (EBV) have been suggested to cause breast cancer, but the evidence that either is associated with breast cancer has been inconsistent (Xue et al, 2003;Glaser et al, 2004;Mant and Cason, 2004;Szabo et al, 2005). Recently, cytomegalovirus (CMV) has been linked to the development of inflammatory diseases and cancer (Söderberg-Naucler, 2006).…”

Human RNA “Rumor” Viruses: the Search for Novel Human Retroviruses in Chronic Disease

“…For example, PCR has been used to link simian virus 40 with a number of human malignancies (168,442). Similarly, Borna disease virus, which naturally infects horses and sheep, has been implicated in schizophrenia on the basis of PCR and serological evidence (461), and the human herpesvirus EBV has been proposed to have a role in breast cancer (15,140,313). For these viruses, additional evidence is still required to provide a solid case for a causal relationship with these diseases.…”

“…The suggestion that a retrovirus related to MMTV might be involved in breast cancer in humans is one of the longestrunning controversies in human retrovirology (313,523). MMTV is a betaretrovirus that causes mammary tumors in mice by the insertional activation of proto-oncogenes (1,84).…”

“…In addition, breast tissue was reported to contain antigens related to the major core protein (CA, p27) of MMTV and MPMV and to SU (gp52) of MMTV (253,332,460,542). Human infection by MMTV was further supported by the detection of anti-Gag and anti-Env antibodies in sera from breast cancer patients (215,313,530).…”