Abstract
We have considered viruses and their contribution to breast cancer.Mouse mammary tumour virusThe prevalence of mouse mammary tumour virus (MMTV) is 15-fold higher in human breast cancer than in normal and benign human breast tissue controls. Saliva is the most plausible means of transmission. MMTV has been identified in dogs, cats, monkeys, mice and rats. The causal mechanisms include insertional oncogenesis and mutations in the protective enzyme ABOBEC3B.Human papilloma virusThe prevalence of high risk human papilloma viruses (HPV) is frequently six fold higher in breast cancer than in normal and benign breast tissue controls. Women who develop HPV associated cervical cancer are at higher than normal risk of developing HPV associated breast cancer. Koilocytes have been identified in breast cancers which is an indication of HPV oncogenicity. The causal mechanisms of HPVs in breast cancer appear to differ from cervical cancer. Sexual activity is the most common form of HPV transmission. HPVs are probably transmitted from the cervix to the breast by circulating extra cellular vesicles.Epstein Barr virusThe prevalence of Epstein Barr virus (EBV) is five fold higher in breast cancer than in normal and benign breast tissue controls. EBV is mostly transmitted from person to person via saliva. EBV infection predisposes breast epithelial cells to malignant transformation through activation of HER2/HER3 signalling cascades. EBV EBNA genes contribute to tumour growth and metastasis and have the ability to affect the mesenchymal transition of cells.Bovine leukemia virusBovine leukemia virus (BLV) infects beef and dairy cattle and leads to various cancers. The prevalence of BLV is double in human breast cancers compared to controls. Breast cancer is more prevalent in red meat eating and cow’s milk consuming populations. BLV may be transmitted to humans from cattle by the consumption of red meat and cow’s milk.ConclusionThe evidence that MMTV, high risk HPVs and EBVs have causal roles in human breast cancer is compelling. The evidence with respect to BLV is more limited but it is likely to also have a causal role in human breast cancer.
Highlights
The purpose of this review is to inform the scientific and general community about the causal role of oncogenic viruses in human breast cancer
This new evidence includes the identification of mouse mammary tumour virus (MMTV) in sporadic breast cancers but not in BRCA1 breast cancers [2]
New case control studies have confirmed that the prevalence of human papilloma viruses (HPVs) in breast cancer is significantly higher than in normal and benign breast tissue controls [4, 5]
Summary
The purpose of this review is to inform the scientific and general community about the causal role of oncogenic viruses in human breast cancer. New evidence has confirmed the role of viruses as the probable underlying cause of breast cancer. This new evidence includes the identification of mouse mammary tumour virus (MMTV) in sporadic breast cancers but not in BRCA1 breast cancers [2]. This indicates that MMTV is an external not genetic causal factor. MMTV has been identified in the teeth of 4500 year old Mediterranean skeletons [3] This is an indication that MMTV has been involved with humans for millenia. New case control studies have confirmed the probable role of bovine leukemia virus (BLV) in human breast cancer [10–12]. BLV has been identified in human blood which suggests a means of internal transmission of this virus to breasts [13]
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