CCR2 and CCR5 genes polymorphisms in benign prostatic hyperplasia and prostate cancer Francis Maria Báo Zambra a , Vanderlei Biolchi b , Ilma Simoni Brum b , José Artur Bogo Chies a,⇑ a Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil b Department of Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil article info Article history: Received 9 November 2012 Accepted 10 April 2013 Available online 28 April 2013 abstract Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are two chronic conditions, very common in aged men, that have been associated to inflammatory process. Chemokines and their receptors are rec- ognized as critical mediators of inflammatory responses, they regulate immune cell migration and are implicated in tumor pathogenesis. The impact of two chemokine receptor gene polymorphisms, CCR2- 64I (rs1799864) and CCR5-D32 (rs333), was evaluated in BPH and PCa. 385 DNA samples (130 BPH, 136 PCa, 119 healthy control) were genotyped. The allele frequencies were similar among control, BPH and PCa groups. Median of serum PSA levels was different between groups: 0.79, 1.45 and 6.91 ng/mL in control, BPH and PCa groups, respectively (all p < 0.001). The prostate volume median was 20.00 cm 3 in the control group, thus, lower than BPH (35.35 cm 3 ) and PCa (35.80 cm 3 ) (both p < 0.001), nevertheless no statistical significant difference was observed between BPH and PCa patients (p = 0.172). Remarkably, CCR2-64I was a protective factor to PCa when compared with BPH (OR = 0.550; 95%CI = 0.311–0.975), although the statistically significant difference was lost after correc- tion for multiple comparisons. No significant associations of CCR5-D32 variant were observed with BPH, PCa or PCa clinicopathologic status. Our data suggest the influence of CCR2-64I variant in the devel- opment of prostate cancer. Ó 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. 1. Introduction Prostate cancer (PCa) is one of the most common cancers in adult male and represents a leading cause of cancer deaths among men worldwide [1,2]. Benign prostatic hyperplasia (BPH) is one of the most frequent proliferative diseases affecting aged men [3,4]. Both conditions are considered chronic diseases with early onset and slow progression [5]. BPH and PCa are also conditions associ- ated with prostatic inflammation, are hormone dependent, their incidence and prevalence rise with the advance of age and, even though there is no clear genetic and molecular relationship be- tween them and considering that both conditions present two dif- ferent pathogenetic pathways, a possible common denominator between them was suggested [6]. Chemokines and chemokine receptors are among factors that may influence PCa and BPH incidence and progression [7,8]. Che- mokines are small chemotactic soluble proteins recognized as crit- ical mediators of inflammatory responses by regulating the migration of immune cells through the interaction with chemokine receptors present on the surface of these cells [9]. These molecules, due to their immunomodulatory activities, are critically involved in processes that allow the development of effective immune re- sponses [9]. Although it is already known that chemokines and chemokine receptors can be involved in tumor pathogenesis, it is not yet clear how they affect human cancer progression. Some con- troversial data exists, since these molecules were already reported as being involved in both tumor development and cancer metasta- sis, as well as in antitumor immune responses [10]. Chemokine receptors are molecules that present seven trans- membrane domains and couples to G-protein for signal transduc- tion [11]. CCR2 is a CC chemokine receptor that can bind CCL2, CCL7, CCL8 and CCL13 chemokines (reviewed by [11]). Among im- mune cells, CCR2 is mainly expressed in macrophages, T lympho- cytes, dendritic cells, B cells and basophils (reviewed by [12]). Recent investigations about PCa and BPH have focused in the CCR2 and its CCL2 ligand, and suggested that CCR2 may contribute to tumor progression [8,13–15]. Regarding this, it was observed 0198-8859/$36.00 - see front matter Ó 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.humimm.2013.04.031 Abbreviations: BPH, benign prostatic hyperplasia; PCa, prostate cancer; CCR, chemokine (C–C motif) receptor; CCL, chemokine (C–C motif) ligand; PSA, prostate- specific antigen. ⇑ Corresponding author. Address: Universidade Federal do Rio Grande do Sul, Departamento de Genética, Instituto de Biociências, Avenida Bento Gonçalves 9500, Prédio 43323, Lab. 212, CEP 91501-970 Agronomia, Porto Alegre, RS, Brazil. Fax: +55 51 3308 7311. E-mail addresses: fbzambra@gmail.com (F.M.B. Zambra), vbiolchi@gmail.com (V. Biolchi), ilma@ufrgs.br (I.S. Brum), jabchies@terra.com.br (J.A.B. Chies). Human Immunology 74 (2013) 1003–1008 Contents lists available at SciVerse ScienceDirect www.ashi-hla.org journal homepage: www.elsevier.com/locate/humimm