DESCRIPTION (provided by applicant): Breast cancer in mice is caused by a virus, mouse mammary tumor virus, and provides a model for a viral etiology of human breast cancer. This virus is transmitted from mother to offspring via milk. Since humans drink more cows' milk than human milk, a bovine virus might be a cause of human breast cancer. Bovine leukemia virus (BLV), an oncogenic retrovirus, causes widespread infection of cattle globally. Leukemia/lymphoma develops in <1% of infected cattle;, most remain healthy, are retained in the herd, and are sources of beef and dairy products. Infectious virus may be present in bovine foodstuffs not adequately cooked or pasteurized. BLV infects lymphocytes and mammary epithelial cells of cattle. It can cross species naturally to infect goats and sheep, and can infect human cells in vitro. Evidence is accumulating that some humans are infected with BLV. Antibodies to BLV were detected in 74% of human volunteers. BLV protein and proviral DNA have been detected in human breast epithelium. Preliminary studies indicate the virus is present more frequently in the breast tissue of women with a diagnosis of breast cancer vs. women who have never had breast cancer. The specific aims of the research proposed here are: 1) to determine the frequency of human leukocyte infecttion with BLV and to obtain preliminary clues about whether infection of leukocytes precedes infection of mammary epithelial cells; 2) to obtain preliminary data to determine if the profile of anti-BLV antibody isotypes (IgG, IgM, IgA) correlates with the presence of BLV proviral DNA in leukocytes and/or the breast tissue. Matched blood and breast tissue samples from the same donor will be obtained from 70 volunteers. Serum IgG, IgM, and IgA antibodies to BLV will be detected by immunoblotting (western blot), and BLV proviral DNA in blood leukocytes and breast tissue will be detected by standard PCR and in situ-PCR. The correlation of antibody presence, BLV infection of leukocytes, BLV infection of breast tissues, and a diagnosis of breast cancer will be tested. The results should provide preliminary data upon which to build a larger study to determine the role of leukocytes in breast tissue infection by BLV and whether tests for anti- BLV antibodies or BLV in leukocytes could serve as possible surrogate markers for BLV infection of breast tissue and be used to predict risk of breast cancer development.
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