title: CCR2-V64I genetic polymorphism: a possible involvement in HER2+ breast cancer.
abstract: Many tumor cells express chemokines and chemokine receptors, and these molecules can affect both tumor progression and anti-tumor immune response. Genetic polymorphisms of some chemokine receptors were found to be closely related to malignant tumors, especially in metastasis process, including breast cancer (BC). Considering this, it was investigated a possible role for CCR2-V64I (C-C chemokine receptor 2) and CCR5-Δ32 (C-C chemokine receptor 5) genetic variants in BC context. Patients were divided into subgroups according to immunohistochemical profile of estrogen (ER) and progesterone (PR) receptors and the human epidermal growth factor receptor 2 (HER2) overexpression. No significant associations were found in relation to susceptibility (CCR2-V64I: OR 1.32; 95 % CI 0.57-3.06; CCR5-∆32: OR 1.04; 95 % CI 0.60-1.81), clinical outcome (tumor size, lymph nodes commitment and/or distant metastasis, TNM staging and nuclear grade) or therapeutic response (recurrence and survival). However, it was found a significant correlation between CCR2-V64I allelic variant and HER2 immunohistochemical positive samples (p = 0.026). All in all, we demonstrate, for the first time, a positive correlation between CCR2 receptor gene polymorphism and a subgroup of BC related to poor prognosis, which deserves further investigation in larger samples for validation.
authors.affiliation: Laboratory of Study and Application of DNA Polymorphisms, Department of Pathological Sciences, Biological Science Center, State University of Londrina, Pr 445 km 380 Celso Garcia Cid Highway, Londrina, PR, 86057-970, Brazil.
authors.forename: Bruna Karina
authors.initials: BK
authors.lastname: Banin-Hirata
authors.affiliation: Laboratory of Study and Application of DNA Polymorphisms, Department of Pathological Sciences, Biological Science Center, State University of Londrina, Pr 445 km 380 Celso Garcia Cid Highway, Londrina, PR, 86057-970, Brazil.
authors.forename: Roberta
authors.initials: R
authors.lastname: Losi-Guembarovski
authors.affiliation: Medicine Course, Federal University of Mato Grosso do Sul, 1662 Capitão Olinto Mancini Avenue, Três Lagoas, MS, 79300-080, Brazil.
authors.forename: Julie Massayo Maeda
authors.initials: JM
authors.lastname: Oda
authors.affiliation: Laboratory of Study and Application of DNA Polymorphisms, Department of Pathological Sciences, Biological Science Center, State University of Londrina, Pr 445 km 380 Celso Garcia Cid Highway, Londrina, PR, 86057-970, Brazil.
authors.forename: Carlos Eduardo Coral
authors.initials: CE
authors.lastname: de Oliveira
authors.affiliation: University Hospital of Londrina, Department of Medical Clinic and Post-Graduate Program of Health Sciences, State University of Londrina, 60 Robert Koch Avenue, Londrina, PR, 86038-440, Brazil.|Cancer Hospital of Londrina, 378 Lucilla Ballalai Street, Londrina, PR, 86015-520, Brazil.
authors.forename: Clodoaldo Zago
authors.initials: CZ
authors.lastname: Campos
authors.affiliation: University Hospital of Londrina, Department of Medical Clinic and Post-Graduate Program of Health Sciences, State University of Londrina, 60 Robert Koch Avenue, Londrina, PR, 86038-440, Brazil.
authors.forename: Tânia Longo
authors.initials: TL
authors.lastname: Mazzuco
authors.affiliation: Department of Basic Health Sciences, State University of Maringá, Colombo Avenue, Maringá, PR, 87020-900, Brazil.
authors.forename: Sueli Donizete
authors.initials: SD
authors.lastname: Borelli
authors.affiliation: Cancer Hospital of Londrina, 378 Lucilla Ballalai Street, Londrina, PR, 86015-520, Brazil.
authors.forename: Jesus Roberto
authors.initials: JR
authors.lastname: Ceribelli
authors.affiliation: Laboratory of Study and Application of DNA Polymorphisms, Department of Pathological Sciences, Biological Science Center, State University of Londrina, Pr 445 km 380 Celso Garcia Cid Highway, Londrina, PR, 86057-970, Brazil. maewat@uel.br.
authors.forename: Maria Angelica Ehara
authors.initials: MA
authors.lastname: Watanabe
mesh_terms: D019943:Amino Acid Substitution; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D050505:Mutant Proteins / Q000235:genetics; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D054390:Receptors, CCR2 / Q000235:genetics*
chemical_list: D050505:Mutant Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D054390:Receptors, CCR2; C515334:CCR2 protein, human; C508053:ERBB2 protein, human
keywords: Breast cancer; CCR2; Clinical outcome; Genetic polymorphism; HER2