Vol. 23, Issue 1: Fall 2015
Bovine Leukemia Virus: A Link Between a Prevalent Virus and Breast Cancer
Could drinking milk increase risk for breast cancer?
Breast cancer is the second most common cancer in women, and was projected to kill 40,290 women in the US in 2015. There are many factors which contribute to and cause breast cancer, and Dr. Gertrude Case Buehring, a professor of virology in the Infectious Diseases and Vaccinology Division of the School of Public Health, is interested in investigating the link between breast cancer and Bovine Leukemia Virus. In her recent study, 239 samples from women with and without a history of breast cancer were analyzed for the presence of Bovine Leukemia Virus (BLV). The results were astounding, because they supported the correlation between bovine leukemia virus and breast cancer development in patients. The next step, which is currently transpiring at Berkeley, is to discover if the virus infected the samples before or after the cancer developed.
Bovine Leukemia is also known as Bovine leukosis, a retrovirus first discovered in Lithuania in 1871, causing B-cell leukemia or lymphosarcoma in cattle. B-cell leukemia is the most common type of cancer of white blood cells. It specifically affects B-Cell lymphocytes, which originate in bone marrow and combat infection in healthy individuals. At the time of its discovery, bovine leukemia virus was thought to be an infectious disease because of how quickly it was able to spread through the cattle herds in Lithuania. The virus was isolated in 1969, and has since been extensively studied. Bovine leukemia virus is not just a retrovirus, but a deltaretrovirus. Deltaretroviruses are very closely related to the human T-cell leukemia virus, and it has genomic region in their DNA that thought to be oncogenic, which means to cause the growth or development of tumors. The genomic region is called Tax, or trans activating region of x-gene. Tax is oncogenic due to its ability to cooperate with other oncogenes, disrupt growth control mechanisms, and disrupt DNA repair. These functions of Tax allow the development of tumors to be widespread and rampant.
However, cancer is not always caused by viruses or retroviruses. Cancer is usually caused by defects in regulatory circuits that govern cell proliferation and homeostasis. Why then, has this random virus from Lithuania virus sparked so much interest? In the most recent study on bovine leukemia virus in dairy cattle completed in 2007, over 82% of the entire US dairy herd from the nation’s 17 major dairy producing farms were sampled. Nearly 84% of the dairy operations sampled tested positive for bovine leukemia virus. Products from animals that develop malignant lymphona and lympho sarcoma cannot be sold on the market, but less than 5% of those animals with BLV develop these conditions. Therefore, products from many of the animals containing the virus are sold to the public. Even more astonishing was that only 7.5% of those sampled had independently reported the presence of BLV in their dairy cows. Moreover, approximately 38% of beef herds and 100% of all large-scale dairy operation herds are infected with the virus. Naturally, concerns were raised about the transmission rates of Bovine leukemia to humans, and consequently 10 studies were completed in the 1970s. These experiments used immunologic methods to test serum samples from 1,761 humans, but none of them tested positive for antibodies for BLV. Therefore, it was concluded that BLV could not be transmitted from animals to humans through consumption. However, since the 1970’s, much more sensitive immunoblot techniques have been made which allowed Berkeley researchers to detect antibodies for BLV in 39% of 257 human volunteers. It was unclear, however, if these antibodies were indeed present in blood serum because of infection with bovine leukemia virus, or only present because of exposure to bovine leukemia virus that had been inactivated with heat in dairy products that were consumed.
To investigate this, researchers injected sheep with pasteurized milk and others with raw milk from Bovine leukemia infected cows. The former did not develop infection and subsequently antibodies, whereas the latter did. Researchers then began to investigate human tissues for evidence of infection with bovine leukemia virus, focusing specifically on breast tissue. Although it is not known exactly how the virus infects breast tissue, it is thought to be through human-to-human transmission, unpasteurized milk, or uncooked meat.
This case-control study from UC Berkeley used “archival formalin fixed paraffin embedded breast tissues” from 239 donor women from the Cooperative Human Tissue Network. In the study, participants were classified as having breast cancer or no history of the disease through a variety of means including medical records and anatomic pathological examination of tissues. Using in situ polymerase chain reaction, which is a DNA diagnostic test to amplify DNA for examination, the exposure of the breast tissue to BLV was determined to be localized within the epithelium of the mammary tissue. It was found that the mammary epithelium for women with breast cancer contained markedly higher concentrations of BLV than did the controls: 59% of the samples with breast cancer had exposure to BLV, whereas only 29% of the tissue samples with no history of the disease showed exposure to BLV.
The most shocking thing about this study, however, is the fact that the odds ratio for the development of breast cancer after exposure to bovine leukemia virus is proportional to that of other recognized risk factors, including obesity, alcohol consumption, hormones, lifestyle, reproductive history. The only risk factors with an odds ratio that exceeded BLV was genetics, familial breast cancer history, high dose ionizing radiation, and age.
Although these findings do not prove that high levels of BLV exposure will guarantee the development of breast cancer, they are very important first steps. If further research shows that BLV is causally linked to breast cancer, then preventative approaches to breast cancer treatment can start to be created. Currently, Dr. Buehring’s laboratory is researching other questions involving this topic. These questions include: does the infection of normal human breast cancer cells with BLV in a culture cause them to acquire the characteristics of a malignant cell? And how exactly do humans become infected with BLV? Can women infected with BLV pass the virus to their children through breast milk or through the placenta? And are other human tissue and organs besides mammary tissue infected by BLV? Once these questions are answered, our understanding of BLV and its link to cancer in humans will be much more defined. If BLV is found to have a causal contribution to cancer, it would have profound implications to public health education and policy. Information about the consumption of contaminated meat and its associated risk with breast cancer should be provided to the public, and it would be imperative that preventative health measures be implemented to increase standards and sanitation of the dairy and meat industry.
About the Author
Chelsea Muennichow is senior molecular cell biology major concentrating in neurobiology and minoring in nutrition. She has been vegan for four years, and loves vegan cooking and baking and animals. She is a certified yoga teacher and loves all things related to reading, writing, health, and wellness. Her future career goals include medical school and/or healthcare administration/consulting, and she can’t wait to travel the world after graduation.