title: HFE Variants and the Expression of Iron-Related Proteins in Breast Cancer-Associated Lymphocytes and Macrophages.
abstract: The association of HFE (High Iron FE) major variants with breast cancer risk and behavior has been a matter of discussion for a long time. However, their impact on the expression of iron-related proteins in the breast cancer tissue has never been addressed. In the present study, hepcidin, ferroportin 1, transferrin receptor 1 (TfR1), and ferritin expressions, as well as tissue iron deposition were evaluated in a collection of samples from breast cancers patients and analyzed according to the patients' HFE genotype. Within the group of patients with invasive carcinoma, those carrying the p.Cys282Tyr variant in heterozygosity presented a higher expression of hepcidin in lymphocytes and macrophages than wild-type or p.His63Asp carriers. An increased expression of TfR1 was also observed in all the cell types analyzed but only in p.Cys282Tyr/p.His63Asp compound heterozygous patients. A differential impact of the two HFE variants was further noticed with the observation of a significantly higher percentage of p.Cys282Tyr heterozygous patients presenting tissue iron deposition in comparison to p.His63Asp heterozygous. In the present cohort, no significant associations were found between HFE variants and classical clinicopathological markers of breast cancer behavior and prognosis. Although limited by a low sampling size, our results provide a new possible explanation for the previously reported impact of HFE major variants on breast cancer progression, i.e., not by influencing systemic iron homeostasis but rather by differentially modulating the local cellular expression of iron-related proteins and tissue iron deposition.
authors.affiliation: Unit for Multidisciplinary Biomedical Research (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal. oamarques@icbas.up.pt.|Lab Immunogenetics & Autoimmu and NeuroScien, UMIB, ICBAS, University of Porto, Porto, Portugal. oamarques@icbas.up.pt.|Pathology and Molecular Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal. oamarques@icbas.up.pt.|Basic and Clinical Research on Iron Biology, Molecular and Cell Biology Institute (IBMC), University of Porto, Porto, Portugal. oamarques@icbas.up.pt.|Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal. oamarques@icbas.up.pt.
authors.forename: Oriana
authors.initials: O
authors.lastname: Marques
authors.affiliation: Pathology and Molecular Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.|Basic and Clinical Research on Iron Biology, Molecular and Cell Biology Institute (IBMC), University of Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Rosa
authors.affiliation: Pathology and Molecular Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Luciana
authors.initials: L
authors.lastname: Leite
authors.affiliation: Human Genetics Department, National Institute of Health Dr. Ricardo Jorge, Lisbon, Portugal.|Institute of Environmental Health, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Faustino
authors.affiliation: Pathology and Molecular Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rêma
authors.affiliation: Unit for Multidisciplinary Biomedical Research (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.|Pathology and Molecular Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Berta
authors.initials: B
authors.lastname: Martins da Silva
authors.affiliation: Pathology and Molecular Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.|Basic and Clinical Research on Iron Biology, Molecular and Cell Biology Institute (IBMC), University of Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal.|Hematology Service, Hospital de Santo António, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Graça
authors.initials: G
authors.lastname: Porto
authors.affiliation: Pathology and Molecular Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.|Department of Pathology, Portuguese Oncology Institute (IPO), Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
keywords: Breast cancer; HFE; Iron; p.Cys282Tyr