No abstract

Bovine leukemia virus (BLV), a deltaretrovirus, causes B-cell leukemia/lymphoma in cattle and is prevalent in herds globally. A previous finding of antibodies against BLV in humans led us to examine the possibility of human infection with BLV. We focused on breast tissue because, in cattle, BLV DNA and protein have been found to be more abundant in mammary epithelium than in lymphocytes. In human breast tissue specimens, we identified BLV DNA by using nested liquid-phase PCR and DNA sequencing. Variations from the bovine reference sequence were infrequent and limited to base substitutions. In situ PCR and immunohistochemical testing localized BLV to the secretory epithelium of the breast. Our finding of BLV in human tissues indicates a risk for the acquisition and proliferation of this virus in humans. Further research is needed to determine whether BLV may play a direct role in human disease.

BackgroundAge, reproductive history, hormones, genetics, and lifestyle are known risk factors for breast cancer, but the agents that initiate cellular changes from normal to malignant are not understood. We previously detected bovine leukemia virus (BLV), a common oncogenic virus of cattle, in the breast epithelium of humans. The objective of this study was to determine whether the presence of BLV DNA in human mammary epithelium is associated with breast cancer.MethodsThis was a case-control study of archival formalin fixed paraffin embedded breast tissues from 239 donors, received 2002–2008 from the Cooperative Human Tissue Network. Case definition as breast cancer versus normal (women with no history of breast cancer) was established through medical records and examination of tissues by an anatomical pathologist. Breast exposure to BLV was determined by in situ-PCR detection of a biomarker, BLV DNA, localized within mammary epithelium.ResultsThe frequency of BLV DNA in mammary epithelium from women with breast cancer (59%) was significantly higher than in normal controls (29%) (multiply- adjusted odds ratio = 3.07, confidence interval = 1.66–5.69, p = .0004, attributable risk = 37%). In women with premalignant breast changes the frequency of BLV DNA was intermediate (38%) between that of women with breast cancer and normal controls (p for trend < .001).ConclusionsAmong the specimens in this study, the presence of amplified BLV DNA was significantly associated with breast cancer. The odds ratio magnitude was comparable to those of well-established breast cancer risk factors related to reproductive history, hormones, and lifestyle and was exceeded only by risk factors related to genetics (familial breast cancer), high dose ionizing radiation, and age. These findings have the potential for primary and secondary prevention of breast cancer.

Identification of the factors responsible for high-risk histological changes may offer new insights into the etiology of breast cancer and potentially lead to the development of methods for its prevention.

Factors that predict outcome after ABO-incompatible RBC transfusions are not well defined. We studied whether the volume of incompatible blood transfused would determine the signs and symptoms and survival outcome for ABO-incompatible RBC transfusions. We reviewed ABO-incompatible RBC transfusions from our institutions and our consultations for 35 years and from a survey of America's Blood Centers' members regarding causes, volume, signs, symptoms, and outcomes of ABO-incompatible RBC transfusions in their service areas from 1995 through 2005. All ABO-incompatible transfusions were due to error; 26 (62%) of 42 occurred at the patient's bedside. Of 36 patients who received more than 50 mL of incompatible blood, 23 (64%) manifested signs or symptoms related to the incompatible transfusion, and 6 (17)% died. Only 3 (25%) of 12 patients who received 50 mL or less of incompatible blood had associated signs or symptoms, and none died. Hypotension, hemoglobinuria, and/or hemoglobinemia were the most frequent findings in survivors and patients who died.ABO-incompatible RBC transfusion does not inevitably mean death or even occurrence of symptoms. Prompt recognition and discontinuation of the transfusion are critical because transfusing less ABO-incompatible blood may minimize signs and symptoms and may prevent death.