Evidence for a causal role by mouse mammary tumour-like virus in human breast cancer

Abstract

We have reviewed the evidence relevant to mouse mammary tumour viruses (MMTV) and human breast cancer. The prevalence of MMTV- like gene sequences is 15-fold higher in human breast cancer than in normal human breast tissue controls and is present in up to 40% of human breast cancers. MMTV-like gene sequences can be identified in benign breast tissues 1–11 years before the development of positive MMTV-like breast cancer in the same women. The prevalence of MMTV antibodies in sera from women with breast cancer is 5-fold higher than in normal women. MMTV can infect human breast epithelial cells and integrate at random into the human genome located in those cells. MMTV-like gene sequences are present in human milk from normal lactating women and with increased prevalence in milk from women at risk of breast cancer. MMTV-like virus associated human breast cancer has strikingly similar features to MMTV-associated mouse mammary tumours. These features include almost identical nucleotide sequences and structure of the MMTV genome, histology, superantigen expression, MMTV infection of B and T lymphocytes and hormone dependence. MMTV-like gene sequences have also been identified in dogs, cats, monkeys, mice and rats. Saliva has been identified as the most plausible means of transmission from human to human and possibly from dogs to humans. The evidence meets the classic causal criteria. A causal role for MMTV-like viruses in human breast cancer is highly likely.