EBV's influence on breast cancer development may soon be understood.
Epstein-Barr virus (EBV), a member of the herpes virus family, is easily transmitted through oral transfer of saliva and by genital secretions.
An incredible 90 percent of all humans on earth are thought to be infected by EBV.
Most sexually active adults will pick up the virus at some point in their lives, and about half of all 5-year-olds have evidence of previous infection.
EBV infects two major cell types, firstly, components of the immune system, known as B cells; secondly, epithelial cells, which line cavities of the body, blood vessels, and organs.
Over the years, EBV has also been associated with a number of specific cancer types such as African Burkitt lymphoma (a cancer of the lymphatics), Hodgkin's disease (a blood cancer), nasopharyngeal carcinoma (a rare head and neck cancer), gastric adenocarcinoma (a type of stomach cancer), and leiomyosarcoma (a smooth muscle tumor).
An estimated 200,000 malignancies are caused by EBV annually.
EBV and breast cancer
Along with the cancers named above, a number of studies have glimpsed a relationship between EBV and breast cancer. Studies carried out in India, North Africa, China, and southern Europe have all noted a relationship.
Although EBV's relationship with cancer generation has been demonstrated, it has proven tough to pin down the processes behind it. Often, the breast cancer will not appear for many years after the initial viral infection, making a causal role difficult to establish.
A team from the Hematology/Oncology Division at Beth Israel Deaconess Medical Center (BIDMC) in Massachusetts, led by Dr. Gerburg Wulf, joined forces with Harvard Medical School in Boston to investigate this puzzle in more detail. The findings are published this week in the journal EBioMedicine.
The researchers cultured breast cells in the presence of EBV; specifically, they used cells known as primary mammary epithelial cells (MECs).
The team found that EBV binds to a specific receptor on normal breast cells called CD21, which leads to infection. The viral infection caused the breast cells to behave like stem cells - they were able to keep on dividing.
Studying EBV and its impacts
Dr. Wulf and his team implanted MECs into mice; they noted that the EBV infection assisted some cancer types, enabling certain proteins to speed up the formation of breast cancer. When the genes of the MECs infected by EBV were examined, they saw genetic characteristics normally associated with a particularly aggressive breast cancer - high-grade, estrogen-receptor-negative breast cancer.
As the authors wrote, "EBV infection of MECs lowers the threshold for malignant transformation." So, although EBV is not a causal factor in itself, it increases the likelihood of developing cancer later in life.
Although the results will need to be replicated and other aspects of the pathway examined, the findings add to our understanding of the causes and influences of breast cancer.
"We think that if a young woman develops EBV during her teenage years or later, her breast epithelial cells will be exposed to the virus and can be infected.
While for most individuals, there will be no long-term consequences, in some, the infection may leave genetic scars and change the metabolism of these cells.
While these are subtle changes, they may, decades later, facilitate breast cancer formation."
Gerburg Wulf, MD, PhD
EBV, it seems, may contribute to breast cancer development by predisposing MECs to become malignant further down the road. However, once cancerous, EBV no longer worsens the disease. The authors point out that the findings add weight to the argument for childhood EBV vaccination. They may also influence the way in which screening is carried out in the future.
Written by Tim Newman