Skip to main content
Erschienen in: Clinical and Experimental Medicine 2/2016

26.02.2015 | Review Article

CCR2-V64I genetic polymorphism: a possible involvement in HER2+ breast cancer

Erschienen in: Clinical and Experimental Medicine | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11 [database on the Internet] 2012. Accessed: 25/01/2014. Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11 [database on the Internet] 2012. Accessed: 25/01/2014.
2.
Zurück zum Zitat Citri A, Skaria KB, Yarden Y. The deaf and the dumb: the biology of ErbB-2 and ErbB-3. Exp Cell Res. 2003;284(1):54–65.CrossRefPubMed Citri A, Skaria KB, Yarden Y. The deaf and the dumb: the biology of ErbB-2 and ErbB-3. Exp Cell Res. 2003;284(1):54–65.CrossRefPubMed
3.
Zurück zum Zitat de la Cruz-Merino L, Barco-Sanchez A, Carrasco FH et al. New insights into the role of the immune microenvironment in breast carcinoma. Clin Dev Immunol. 2013. de la Cruz-Merino L, Barco-Sanchez A, Carrasco FH et al. New insights into the role of the immune microenvironment in breast carcinoma. Clin Dev Immunol. 2013.
4.
Zurück zum Zitat Charo IF, Myers SJ, Herman A, Franci C, Connolly AJ, Coughlin SR. Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails. Proc Natl Acad Sci USA. 1994;91(7):2752–6.CrossRefPubMedPubMedCentral Charo IF, Myers SJ, Herman A, Franci C, Connolly AJ, Coughlin SR. Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails. Proc Natl Acad Sci USA. 1994;91(7):2752–6.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Sanders SK, Crean SM, Boxer PA, Kellner D, LaRosa GJ, Hunt SW. Functional differences between monocyte chemotactic protein-1 receptor A and monocyte chemotactic protein-1 receptor B expressed in a Jurkat T cell. J Immunol. 2000;165(9):4877–83.CrossRefPubMed Sanders SK, Crean SM, Boxer PA, Kellner D, LaRosa GJ, Hunt SW. Functional differences between monocyte chemotactic protein-1 receptor A and monocyte chemotactic protein-1 receptor B expressed in a Jurkat T cell. J Immunol. 2000;165(9):4877–83.CrossRefPubMed
6.
Zurück zum Zitat Fang WB, Jokar I, Zou A, Lambert D, Dendukuri P, Cheng N. CCL2/CCR2 chemokine signaling coordinates survival and motility of breast cancer cells through Smad3 protein- and p42/44 mitogen-activated protein kinase (MAPK)-dependent mechanisms. J Biol Chem. 2012;287(43):36593–608.CrossRefPubMedPubMedCentral Fang WB, Jokar I, Zou A, Lambert D, Dendukuri P, Cheng N. CCL2/CCR2 chemokine signaling coordinates survival and motility of breast cancer cells through Smad3 protein- and p42/44 mitogen-activated protein kinase (MAPK)-dependent mechanisms. J Biol Chem. 2012;287(43):36593–608.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Loetscher P, Uguccioni M, Bordoli L, Baggiolini M, Moser B. CCR5 is characteristic of Th1 lymphocytes. Nature. 1998;391(6665):344–5.CrossRefPubMed Loetscher P, Uguccioni M, Bordoli L, Baggiolini M, Moser B. CCR5 is characteristic of Th1 lymphocytes. Nature. 1998;391(6665):344–5.CrossRefPubMed
8.
Zurück zum Zitat Manes S, Mira E, Colomer R, et al. CCR5 expression influences the progression of human breast cancer in a p53-dependent manner. J Exp Med. 2003;198(9):1381–9.CrossRefPubMedPubMedCentral Manes S, Mira E, Colomer R, et al. CCR5 expression influences the progression of human breast cancer in a p53-dependent manner. J Exp Med. 2003;198(9):1381–9.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Velasco-Velazquez M, Jiao XM, De la Fuente M, et al. CCR5 antagonist blocks metastasis of basal breast cancer cells. Cancer Res. 2012;72(15):3839–50.CrossRefPubMed Velasco-Velazquez M, Jiao XM, De la Fuente M, et al. CCR5 antagonist blocks metastasis of basal breast cancer cells. Cancer Res. 2012;72(15):3839–50.CrossRefPubMed
11.
Zurück zum Zitat Ugurel S, Schrama D, Keller G, et al. Impact of the CCR5 gene polymorphism on the survival of metastatic melanoma patients receiving immunotherapy. Cancer Immunol Immunother. 2008;57(5):685–91.CrossRefPubMed Ugurel S, Schrama D, Keller G, et al. Impact of the CCR5 gene polymorphism on the survival of metastatic melanoma patients receiving immunotherapy. Cancer Immunol Immunother. 2008;57(5):685–91.CrossRefPubMed
12.
Zurück zum Zitat Chen MK, Yeh KT, Chiou HL, Lin CW, Chung TT, Yang SF. CCR2-64I gene polymorphism increase susceptibility to oral cancer. Oral Oncol. 2011;47(7):577–82.CrossRefPubMed Chen MK, Yeh KT, Chiou HL, Lin CW, Chung TT, Yang SF. CCR2-64I gene polymorphism increase susceptibility to oral cancer. Oral Oncol. 2011;47(7):577–82.CrossRefPubMed
13.
Zurück zum Zitat Kucukgergin C, Isman FK, Cakmakoglu B, Sanli O, Seckin S. Association of polymorphisms in MCP-1, CCR2, and CCR5 genes with the risk and clinicopathological characteristics of prostate cancer. DNA Cell Biol. 2012;31(8):1418–24.CrossRefPubMed Kucukgergin C, Isman FK, Cakmakoglu B, Sanli O, Seckin S. Association of polymorphisms in MCP-1, CCR2, and CCR5 genes with the risk and clinicopathological characteristics of prostate cancer. DNA Cell Biol. 2012;31(8):1418–24.CrossRefPubMed
14.
Zurück zum Zitat Nakayama EE, Tanaka Y, Nagai Y, Iwamoto A, Shioda T. A CCR2-V641 polymorphism affects stability of CCR2A isoform. Aids. 2004;18(5):729–38.CrossRefPubMed Nakayama EE, Tanaka Y, Nagai Y, Iwamoto A, Shioda T. A CCR2-V641 polymorphism affects stability of CCR2A isoform. Aids. 2004;18(5):729–38.CrossRefPubMed
15.
Zurück zum Zitat Kostrikis LG, Huang YX, Moore JP, et al. A chemokine receptor CCR2 allele delays HIV-1 disease progression and is associated with a CCR5 promoter mutation. Nat Med. 1998;4(3):350–3.CrossRefPubMed Kostrikis LG, Huang YX, Moore JP, et al. A chemokine receptor CCR2 allele delays HIV-1 disease progression and is associated with a CCR5 promoter mutation. Nat Med. 1998;4(3):350–3.CrossRefPubMed
16.
Zurück zum Zitat Barmania F, Pepper M. C–C chemokine receptor type five (CCR5): an emerging target for the control of HIV infection. Appl Transl Genomics. 2013;2:3–16.CrossRef Barmania F, Pepper M. C–C chemokine receptor type five (CCR5): an emerging target for the control of HIV infection. Appl Transl Genomics. 2013;2:3–16.CrossRef
17.
Zurück zum Zitat Zafiropoulos A, Crikas N, Passam AM, Spandidos DA. Significant involvement of CCR2-64I and CXCL12-3a in the development of sporadic breast cancer. J Med Genet. 2004;41(5). Zafiropoulos A, Crikas N, Passam AM, Spandidos DA. Significant involvement of CCR2-64I and CXCL12-3a in the development of sporadic breast cancer. J Med Genet. 2004;41(5).
18.
Zurück zum Zitat Span PN, Pollakis G, Paxton WA et al. Improved metastasis-free survival in nonadjuvantly treated postmenopausal breast cancer patients with chemokine receptor 5 del32 frameshift mutations. Int J Cancer. 2014. Span PN, Pollakis G, Paxton WA et al. Improved metastasis-free survival in nonadjuvantly treated postmenopausal breast cancer patients with chemokine receptor 5 del32 frameshift mutations. Int J Cancer. 2014.
19.
Zurück zum Zitat Sobin LH, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumours. 7th ed. Oxford: Wiley-Blackwell; 2009. Sobin LH, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumours. 7th ed. Oxford: Wiley-Blackwell; 2009.
20.
Zurück zum Zitat Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997–4013.CrossRefPubMed Wolff AC, Hammond ME, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997–4013.CrossRefPubMed
21.
Zurück zum Zitat Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28(16):2784–95.CrossRefPubMedPubMedCentral Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28(16):2784–95.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Aoki MN, da Silva do Amaral Herrera AC, Amarante MK, do Val Carneiro JL, Fungaro MH, Watanabe MA. CCR5 and p53 codon 72 gene polymorphisms: implications in breast cancer development. Int J Mol Med. 2009;23(3):429–35.PubMed Aoki MN, da Silva do Amaral Herrera AC, Amarante MK, do Val Carneiro JL, Fungaro MH, Watanabe MA. CCR5 and p53 codon 72 gene polymorphisms: implications in breast cancer development. Int J Mol Med. 2009;23(3):429–35.PubMed
23.
Zurück zum Zitat Sezgin I, Koksal B, Bagci G, Kurtulgan HK, Ozdemir O. CCR2 polymorphism in chronic renal failure patients requiring long-term hemodialysis. Intern Med. 2011;50(21):2457–61.CrossRefPubMed Sezgin I, Koksal B, Bagci G, Kurtulgan HK, Ozdemir O. CCR2 polymorphism in chronic renal failure patients requiring long-term hemodialysis. Intern Med. 2011;50(21):2457–61.CrossRefPubMed
24.
Zurück zum Zitat Rodriguez S, Gaunt TR, Day IN. Hardy–Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol. 2009;169(4):505–14.CrossRefPubMedPubMedCentral Rodriguez S, Gaunt TR, Day IN. Hardy–Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol. 2009;169(4):505–14.CrossRefPubMedPubMedCentral
25.
26.
Zurück zum Zitat Zhang YM, Yao F, Yao XL, et al. Role of CCL5 in invasion, proliferation and proportion of CD44 +/CD24(−) phenotype of MCF-7 cells and correlation of CCL5 and CCR5 expression with breast cancer progression. Oncol Rep. 2009;21(4):1113–21.CrossRefPubMed Zhang YM, Yao F, Yao XL, et al. Role of CCL5 in invasion, proliferation and proportion of CD44 +/CD24(−) phenotype of MCF-7 cells and correlation of CCL5 and CCR5 expression with breast cancer progression. Oncol Rep. 2009;21(4):1113–21.CrossRefPubMed
27.
28.
Zurück zum Zitat Attar R, Agachan B, Kuran SB, et al. Association of CCL2 and CCR2 gene variants with endometrial cancer in Turkish women. In vivo. 2010;24(2):243–8.PubMed Attar R, Agachan B, Kuran SB, et al. Association of CCL2 and CCR2 gene variants with endometrial cancer in Turkish women. In vivo. 2010;24(2):243–8.PubMed
29.
Zurück zum Zitat Yeh CB, Tsai HT, Chen YC, et al. Genetic polymorphism of CCR2-64I increased the susceptibility of hepatocellular carcinoma. J Surg Oncol. 2010;102(3):264–70.CrossRefPubMed Yeh CB, Tsai HT, Chen YC, et al. Genetic polymorphism of CCR2-64I increased the susceptibility of hepatocellular carcinoma. J Surg Oncol. 2010;102(3):264–70.CrossRefPubMed
30.
Zurück zum Zitat Zheng B, Wiklund F, Gharizadeh B, et al. Genetic polymorphism of chemokine receptors CCR2 and CCR5 in Swedish cervical cancer patients. Anticancer Res. 2006;26(5B):3669–74.PubMed Zheng B, Wiklund F, Gharizadeh B, et al. Genetic polymorphism of chemokine receptors CCR2 and CCR5 in Swedish cervical cancer patients. Anticancer Res. 2006;26(5B):3669–74.PubMed
31.
Zurück zum Zitat Guleria K, Sharma S, Manjari M. Uppal MS, Singh NR, Sambyal V. p. R72P, PIN3 Ins16 bp Polymorphisms of TP53 and CCR5 Delta 32 in North Indian Breast Cancer Patients. Asian Pac J Cancer. 2012;13(7):3305–11.CrossRef Guleria K, Sharma S, Manjari M. Uppal MS, Singh NR, Sambyal V. p. R72P, PIN3 Ins16 bp Polymorphisms of TP53 and CCR5 Delta 32 in North Indian Breast Cancer Patients. Asian Pac J Cancer. 2012;13(7):3305–11.CrossRef
32.
Zurück zum Zitat Degerli N, Yilmaz E, Bardakci F. The Delta 32 allele distribution of the CCR5 gene and its relationship with certain cancers in a Turkish population. Clin Biochem. 2005;38(3):248–52.CrossRefPubMed Degerli N, Yilmaz E, Bardakci F. The Delta 32 allele distribution of the CCR5 gene and its relationship with certain cancers in a Turkish population. Clin Biochem. 2005;38(3):248–52.CrossRefPubMed
33.
Zurück zum Zitat Gharagozloo M, Doroudchi M, Farjadian S, Pezeshki AM, Ghaderi A. The frequency of CCR5Delta32 and CCR2-64I in southern Iranian normal population. Immunol Lett. 2005;96(2):277–81.CrossRefPubMed Gharagozloo M, Doroudchi M, Farjadian S, Pezeshki AM, Ghaderi A. The frequency of CCR5Delta32 and CCR2-64I in southern Iranian normal population. Immunol Lett. 2005;96(2):277–81.CrossRefPubMed
34.
Zurück zum Zitat Slamon DJ, Godolphin W, Jones LA, et al. Studies of the Her-2/Neu proto-oncogene in human-breast and ovarian-cancer. Science. 1989;244(4905):707–12.CrossRefPubMed Slamon DJ, Godolphin W, Jones LA, et al. Studies of the Her-2/Neu proto-oncogene in human-breast and ovarian-cancer. Science. 1989;244(4905):707–12.CrossRefPubMed
35.
Zurück zum Zitat Bosher JM, Williams T, Hurst HC. The developmentally-regulated transcription factor Ap-2 Is involved in C-Erbb-2 overexpression in human mammary-carcinoma. Proc Natl Acad Sci USA. 1995;92(3):744–7.CrossRefPubMedPubMedCentral Bosher JM, Williams T, Hurst HC. The developmentally-regulated transcription factor Ap-2 Is involved in C-Erbb-2 overexpression in human mammary-carcinoma. Proc Natl Acad Sci USA. 1995;92(3):744–7.CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Jimenez F, Quinones MP, Martinez HG, et al. CCR2 plays a critical role in dendritic cell maturation: possible role of CCL2 and NF-kappa B. J Immunol. 2010;184(10):5571–81.CrossRefPubMedPubMedCentral Jimenez F, Quinones MP, Martinez HG, et al. CCR2 plays a critical role in dendritic cell maturation: possible role of CCL2 and NF-kappa B. J Immunol. 2010;184(10):5571–81.CrossRefPubMedPubMedCentral
37.
Metadaten
Titel
CCR2-V64I genetic polymorphism: a possible involvement in HER2+ breast cancer
Publikationsdatum
26.02.2015
Erschienen in
Clinical and Experimental Medicine / Ausgabe 2/2016
Print ISSN: 1591-8890
Elektronische ISSN: 1591-9528
DOI
https://doi.org/10.1007/s10238-015-0342-9

Weitere Artikel der Ausgabe 2/2016

Clinical and Experimental Medicine 2/2016 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.