Abstract
Bovine leukemia virus (BLV) is a retrovirus that causes lymphoma in cattle worldwide and has also been associated with breast cancer in humans. The mechanism of BLV infection in humans and its implication as a primary cause of cancer in women are not known yet. BLV infection in humans may be caused by the consumption of milk and milk-products or meat from infected animals. Breast cancer incidence rates in Brazil are high, corresponding to 29.5% a year of cancer cases among women. In 2020, an estimated 66,280 new cases of breast cancer are expected, whereas in 2018 breast cancer has led to 17,572 deaths, the highest incidence and lethality among cancers in women in this country that year. BLV infection occurrence ranges from 60 to 95% in dairy herds. In addition, there are some regions, such as the Minas Gerais State, southeastern Brazil, where the population traditionally consume unpasteurized dairy products. Taken together, this study aimed to verify if there is a higher association between breast cancer and the presence of BLV genome in breast tissue samples within this population that consumes raw milk from animals with high rates of BLV infection. A molecular study of two BLV genes was carried out in 88 breast parenchyma samples, between tumors and controls. The amplified fragment was subjected to BLV proviral sequencing and its identity was confirmed using GenBank. BLV proviral genes were amplified from tumor breast parenchyma samples and healthy tissue control samples from women, revealing a 95.9% (47/49) and 59% (23/39) positivity, respectively. Our results show the highest correlation of BLV and human breast cancer found in the world to date within the population of Minas Gerais, Brazil.
Highlights
Breast cancer has a high incidence among Brazilian women, corresponding to 29.5% of the cancer cases in 2018 of which 25% evolve to terminal illnesses and death [1]
The amplifications of the Beta actin gene can be seen in S1 Fig. As can be seen in S2 and S3 Figs, no individual positive for HIV or Human T leukemia virus (HTLV) presented amplification related to Bovine leukemia virus (BLV)-tax (113 bp) or BLV-env (165 bp) respectively
In the case of Polymerase Chain Reaction (PCR) for BLV-env, some non-specific amplicons can be seen on the gel (S3 Fig) and we think that it was due to the origin of the samples (PBMC Deoxyribonucleic acid (DNA)), which were far better preserved than samples of formalin-fixed and paraffinized tissues, such as the samples of breast tissue used in this work
Summary
Breast cancer has a high incidence among Brazilian women, corresponding to 29.5% of the cancer cases in 2018 of which 25% evolve to terminal illnesses and death [1]. Some viruses have been found in the human breast parenchyma such as Mouse mammary tumor virus (MMTV), Epstein-Barr virus (EBV), and Human papillomavirus (HPV) in both healthy and cancerous samples [4]. In the USA, 59% of breast tumor tissues have been BLV positive versus 29% for control tissues [5]. These data have been contested by Chinese researchers who have not found a single positive case for BLV in human breast parenchyma of 91 patients with breast tumors using RT-PCR and ELISA [10]. In Colombia, in a retrospective study, the positivity for the BLV genome in healthy tissues was markedly greater than in tumor tissues [13]. The geographic location of patients, extraction methodology, and amplification of BLV genomic material in these samples may explain the differences in the obtained results, but further investigation is still needed on this subject
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