A new paper presents a surprising breast cancer cause

A paper in The Bosnian Journal of Basic Medical Sciences presents a surprising answer to the question: what causes breast cancer in most patients?

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VALLEY COTTAGE, N.Y.—Today The Center for the Biology of Chronic Disease (CBCD) has announced the publication of a new paper by Hanan Polansky and Hava Schwab in the science journal The Bosnian Journal of Basic Medical Sciences. The research answers one of the bigger question in breast cancer today: what causes breast cancer in most patients? 
Scientists know that certain genetic mutations in genes, such as the famous BRCA1, can cause breast cancer. However, only a small proportion of breast cancer has a hereditary cause — around five to ten percent. This means that a small number of patients have a mutation in their genes. Most patients don't have any mutations. Currently the factor that causes breast cancer in the majority of breast cancer patients is unknown, but the new paper may have identified it. 
According to the paper, certain latent viruses can disrupt the expression of certain genes, including the BRCA1 gene, and cause breast cancer. These viruses interact with a unique human factor called GABP, which turns on the BRCA1 gene.
“GA binding protein (GABP) is a transcription factor composed of two subunits, GABPα and GABPβ. GABP binds the cis-regulatory element called the N-box. GABP is responsible for the regulation of a variety of cellular genes related to growth, respiration, and cell differentiation.
Several studies showed that GABP transactivates the BRCA1 gene,” notes the paper.
The virus prevents GABP from turning on BRCA1, which causes a decrease in BRCA1 expression, and breast cancer. The paper identifies human papillomaviruses (HPV), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and other viruses as those that interact with GABP factor. 

“A systematic review and meta-analysis of 29 studies that included 2,211 breast tissue samples from across the globe found that 23% of breast cancer patients had HPV DNA compared to 12.9% in controls,” the paper continues. “Also, the researchers pooled the data of nine case control studies and calculated an odds ratio of 5.9, indicating that HPV positive women are 5.9 times more likely to have breast cancer. Furthermore, a case control study in northern Iran, with 130 individuals, used PCR analysis and detected HPV DNA in 25.9% of breast cancer patients tumors compared to 2.4% in non-cancer patients breast tissue, where most of the HPV types detected were the ‘high risk’ HPV subtypes, such as HPV-16 and 18. The high prevalence of HPV-positive DNA in breast cancer patients suggests a possible link between HPV and breast cancer. Furthermore, it has been shown that the E6 and E7 oncoproteins of HPV-16 and 18 directly interact with and inactivate BRCA1 in breast cancer cells.”

“Studies also found EBV in breast cancer patients. One European study, which included 196 breast cancer specimens, found EBV DNA in 33.2% of the cases using real-time quantitative PCR (RT-PCR). Interestingly, the EBV-positive breast cancers tended to be tumors with a more aggressive phenotype. These EBV-positive tumors were also more frequently estrogen receptor negative, and had a higher histological grade. A large meta-analysis of 24 studies, which included 1,535 cases from all over the world, found an EBV infection in 29.3% of the patients with breast cancer. Also, patients with a positive EBV status showed a significant increase in breast malignancy risk (OR=6.3),” the paper says. “These studies provide evidence that EBV is statistically associated with an increased in breast cancer risk, especially some specific types of breast cancer, such as lobular breast carcinoma.”
It is well known that most people have at least one of the viruses that interact with GABP.  The question is why only a few develop breast cancer. The number of viruses is critical. An individual may be infected with the virus and still be healthy. The copy number in a cell, also called viral load, viral burden or viral titer, is the determining factor. According to the paper, an increase in the copy number of latent viruses increases the risk of breast cancer.

“Many events can increase the copy number of the virus during the latent phase,” mentions the paper. “For instance, aging, certain medications, surgery, chemotherapy, radiation, and stress can decrease the efficiency of the immune system and increase the copy number of the latent virus.”
According to another paper by Hanan Polansky, recently published in the medical journal Oncotarget, “When such an event occurs, the efficiency of the immune system decreases, the copy number of the latent viruses increases, and the risk of cancer also increases.” In other words, these events damage the immune system, increase the copy number of latent viruses hiding in the cell and increase the risk of breast cancer.
As of now, there are no approved drugs that target latent viruses.  The current antiviral drugs only target replicating viruses, or viruses that are in an active state.

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