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      High positivity values for bovine leukemia virus in human breast cancer cases from Minas Gerais, Brazil

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          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.

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          pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up

          Morphological assessment of the degree of differentiation has been shown in numerous studies to provide useful prognostic information in breast cancer, but until recently histological grading has not been accepted as a routine procedure, mainly because of perceived problems with reproducibility and consistency. In the Nottingham/Tenovus Primary Breast Cancer Study the most commonly used method, described by Bloom & Richardson, has been modified in order to make the criteria more objective. The revised technique involves semiquantitative evaluation of three morphological features--the percentage of tubule formation, the degree of nuclear pleomorphism and an accurate mitotic count using a defined field area. A numerical scoring system is used and the overall grade is derived from a summation of individual scores for the three variables: three grades of differentiation are used. Since 1973, over 2200 patients with primary operable breast cancer have been entered into a study of multiple prognostic factors. Histological grade, assessed in 1831 patients, shows a very strong correlation with prognosis; patients with grade I tumours have a significantly better survival than those with grade II and III tumours (P less than 0.0001). These results demonstrate that this method for histological grading provides important prognostic information and, if the grading protocol is followed consistently, reproducible results can be obtained. Histological grade forms part of the multifactorial Nottingham prognostic index, together with tumour size and lymph node stage, which is used to stratify individual patients for appropriate therapy.
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            Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer

            Importance Germline pathogenic variants in BRCA1 and BRCA2 predispose to an increased lifetime risk of breast cancer. However, the relevance of germline variants in other genes from multigene hereditary cancer testing panels is not well defined. Objective To determine the risks of breast cancer associated with germline variants in cancer predisposition genes. Design, Setting, and Participants A study population of 65 057 patients with breast cancer receiving germline genetic testing of cancer predisposition genes with hereditary cancer multigene panels. Associations between pathogenic variants in non-BRCA1 and non-BRCA2 predisposition genes and breast cancer risk were estimated in a case-control analysis of patients with breast cancer and Exome Aggregation Consortium reference controls. The women underwent testing between March 15, 2012, and June 30, 2016. Main Outcomes and Measures Breast cancer risk conferred by pathogenic variants in non-BRCA1 and non-BRCA2 predisposition genes. Results The mean (SD) age at diagnosis for the 65 057 women included in the analysis was 48.5 (11.1) years. The frequency of pathogenic variants in 21 panel genes identified in 41 611 consecutively tested white women with breast cancer was estimated at 10.2%. After exclusion of BRCA1, BRCA2 , and syndromic breast cancer genes ( CDH1, PTEN , and TP53 ), observed pathogenic variants in 5 of 16 genes were associated with high or moderately increased risks ofbreast cancer: ATM (OR, 2.78; 95% CI, 2.22-3.62), BARD1 (OR, 2.16; 95% CI, 1.31-3.63), CHEK2 (OR, 1.48; 95% CI, 1.31-1.67), PALB2 (OR, 7.46; 95% CI, 5.12-11.19), and RAD51D (OR, 3.07; 95% CI, 1.21-7.88). Conversely, variants in the BRIP1 and RAD51C ovarian cancer risk genes; the MREHA, RAD50 , and NBN MRN complex genes; the MLH1 and PMS2 mismatch repair genes; and NF1 were not associated with increased risks of breast cancer. Conclusions and Relevance This study establishes several panel genes as high- and moderate-risk breast cancer genes and provides estimates of breast cancer risk associated with pathogenic variants in these genes among individuals qualifying for clinical genetic testing.
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              Mechanisms of leukemogenesis induced by bovine leukemia virus: prospects for novel anti-retroviral therapies in human

              In 1871, the observation of yellowish nodules in the enlarged spleen of a cow was considered to be the first reported case of bovine leukemia. The etiological agent of this lymphoproliferative disease, bovine leukemia virus (BLV), belongs to the deltaretrovirus genus which also includes the related human T-lymphotropic virus type 1 (HTLV-1). This review summarizes current knowledge of this viral system, which is important as a model for leukemogenesis. Recently, the BLV model has also cast light onto novel prospects for therapies of HTLV induced diseases, for which no satisfactory treatment exists so far.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: Formal analysisRole: Methodology
                Role: Methodology
                Role: Methodology
                Role: Formal analysisRole: Investigation
                Role: MethodologyRole: Visualization
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Formal analysis
                Role: ValidationRole: Visualization
                Role: InvestigationRole: Methodology
                Role: ConceptualizationRole: ValidationRole: Visualization
                Role: ConceptualizationRole: Supervision
                Role: ValidationRole: Visualization
                Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                5 October 2020
                2020
                : 15
                : 10
                : e0239745
                Affiliations
                [1 ] Laboratório de Retroviroses—Departamento de Medicina Veterinária Preventiva, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
                [2 ] Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Belo Horizonte, Minas Gerais, Brazil
                [3 ] Departamento de Anatomia Patológica e Medicina Legal, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
                Consejo Nacional de Investigaciones Cientificas y Tecnicas, ARGENTINA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-3947-5962
                http://orcid.org/0000-0003-0395-358X
                Article
                PONE-D-20-13532
                10.1371/journal.pone.0239745
                7535047
                33017448
                5f5f029b-6635-4012-ab80-81632273bbc0
                © 2020 Delarmelina et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 May 2020
                : 11 September 2020
                Page count
                Figures: 1, Tables: 3, Pages: 12
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004901, Fundação de Amparo à Pesquisa do Estado de Minas Gerais;
                Award ID: APQ-01814-16
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100003593, Conselho Nacional de Desenvolvimento Científico e Tecnológico;
                Award ID: 305733/2019-2
                Award Recipient :
                JKPR and RCL are CNPq fellowship recipients. JKPR - FAPEMIG - Grant number APQ-01814-16 Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) - Web site: www.fapemig.br The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Breast Tumors
                Breast Cancer
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Carcinoma
                Hepatocellular Carcinoma
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Gastrointestinal Tumors
                Hepatocellular Carcinoma
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Hepatocellular Carcinoma
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Research and Analysis Methods
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Biology and Life Sciences
                Nutrition
                Diet
                Beverages
                Milk
                Breast Milk
                Medicine and Health Sciences
                Nutrition
                Diet
                Beverages
                Milk
                Breast Milk
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Milk
                Breast Milk
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Milk
                Breast Milk
                Biology and Life Sciences
                Physiology
                Body Fluids
                Milk
                Breast Milk
                Medicine and Health Sciences
                Oncology
                Basic Cancer Research
                Cancer Genomics
                Biology and Life Sciences
                Genetics
                Genomics
                Genomic Medicine
                Cancer Genomics
                People and places
                Geographical locations
                South America
                Brazil
                Research and analysis methods
                Extraction techniques
                DNA extraction
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Bovines
                Cattle
                Biology and Life Sciences
                Zoology
                Animals
                Vertebrates
                Amniotes
                Mammals
                Bovines
                Cattle
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Ruminants
                Cattle
                Biology and Life Sciences
                Zoology
                Animals
                Vertebrates
                Amniotes
                Mammals
                Ruminants
                Cattle
                Custom metadata
                Sequence data are available on NCBI GenBank (accession numbers MN128450-MN128470). All other relevant data are within the manuscript and its supporting Information files.

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