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.npj Breast Cancer (2019) 5:40 ; https://doi.

Catching viral breast cancer

“…Reviews of case control studies of viruses and breast cancer have been previously conducted. These include (i) MMTV by Lawson & Glenn 2019 [14], (ii) HPVs by Ren et al (2019) [15], (iii) EBV Lawson et al 2018 [1], (iv) BLV by Buehring & Sans 2019 [16]. The details in these case control studies have been included as Supplementary Tables.…”

Presence of high-risk HPVs, EBV, and MMTV in human triple-negative breast cancer

“…Purified genomic DNA from each sample was analyzed for HPVs, EBV, and MMTV-like virus by polymerase chain reaction (PCR) using specific primers for high-risk HPV types: 16,18,31,33,35,39,45,51,52,56,58,59, 66 and 68 as well as EBNA1, EBNA2 (Forward primer: 5′-AGGGATGCCTGGACACAAGA-3′ and Reverse primer: 5′-TTGTGACAGAGGTGACAAAA-3′) and LMP1 of EBV as previously described. 50,51 In addition, PCR was performed for MMTV (Forward primer: 5′-GATGGTATGAAGCAGGATGG-3′ and Reverse primer: 5′-CCTCTTTTCTCTATATCTATTAGCTGAGGTAATC-3′).…”

“…[35][36][37][38] However, a few studies failed to detect the presence of these oncoviruses in human breast cancer as well as normal mammary tissues. [39][40][41] Based on previous reports depicting the role of HPVs, EBV, and MMTV-like virus in the initiation of various cancers, comprising breast, 19,30,[36][37][38][42][43][44][45] we explored the presence/co-presence of high-risk HPVs, EBV, and MMTV-like virus in TNBC samples in Croatian women.…”

Mouse Mammary Tumor Virus (MMTV)-Like env Sequence in Brazilian Breast Cancer Samples: Implications in Clinicopathological Parameters in Molecular Subtypes

“…Liu et al [19] were able to isolate a complete provirus from human BC samples and Lawson et al [20] found MMTV-like antigens and sequences in benign lesions from women that developed BC years later. Furthermore, MMTV-like sequences were found in other human biological samples, such as milk [21], saliva [22], and peripheral blood lymphoid cells [23,24], suggesting that viral transmission and spreading in humans are similar to that described in mice, occurring via breast-feeding and infection of mucosa-associated lymphocytes before reaching the breast tissue [25].…”