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      –2518 A/G MCP-1 but not –403 G/A RANTES gene polymorphism is associated with enhanced risk of basal cell carcinoma

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          Abstract

          Introduction

          Polymorphic variants of MCP-1 and RANTES genes and their protein serum levels have been implicated in the increased risk and severity of several malignancies. However, the subject has not been explored in basal cell carcinoma (BCC) patients so far.

          Aim

          To investigate the association between monocyte chemoattractant protein 1 (MCP-1) (–2518 A/G) and RANTES (–403 G/A) polymorphism and risk and clinical course of BCC.

          Material and methods

          The study group consisted of 150 unrelated patients with BCC and 140 healthy, unrelated, age- and sex-matched volunteers. The polymorphisms were analysed using the amplification refractory mutation system polymerase chain reaction method (ARMS-PCR) and single specific primer-polymerase chain reaction (SSP-PCR). Serum cytokine levels were measured with ELISA.

          Results

          The presence of the MCP-1 –2518 GG genotype was statistically more frequent in BCC patients and it increased the risk of BCC (OR = 2.63, p = 0.003). Genotype –330 GG was statistically more common in patients with less advanced tumours (OR = 2.8, p = 0.017). Monocyte chemoattractant protein 1 serum level was statistically higher with GG genotype. In the BCC group MCP-1 serum levels were decreased. Neither polymorphic variants of RANTES nor the chemokine serum concentration differed significantly between the study groups.

          Conclusions

          These findings suggest that –2518 A/G MCP-1 polymorphism may be involved in BCC pathogenesis.

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          Most cited references34

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          Cancer-related inflammation.

          The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
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            Cytokine patterns in patients with cancer: a systematic review.

            Active, but dysfunctional, immune responses in patients with cancer have been studied in several tumour types, but owing to the heterogeneity of cancer theories of common reaction mechanisms seem to be obsolete. In this Review of published clinical studies of patients with cancer, expression and interplay of the following cytokines are examined: interleukin 2, interleukin 6, interleukin 8, interleukin 10, interleukin 12, interleukin 18, tumour necrosis factor α (TNFα), transforming growth factor β (TGFβ), interferon-γ, HLA-DR, macrophage migration inhibitory factor (MIF), and C-X-C motif chemokine receptor 4 (CXCR4). Clinical data were analysed in a non-quantitative descriptive manner and interpreted with regard to experimentally established physiological cytokine interactions. The clinical cytokine pattern that emerged suggests that simultaneous immunostimulation and immunosuppression occur in patients with cancer, with increased concentrations of the cytokines MIF, TNFα, interleukin 6, interleukin 8, interleukin 10, interleukin 18, and TGFβ. This specific cytokine pattern seems to have a prognostic effect, since high interleukin 6 or interleukin 10 serum concentrations are associated with negative prognoses in independent cancer types. Although immunostimulatory cytokines are involved in local cancer-associated inflammation, cancer cells seem to be protected from immunological eradication by cytokine-mediated local immunosuppression and a resulting defect of the interleukin 12-interferon-γ-HLA-DR axis. Cytokines produced by tumours might have a pivotal role in this defect. A working hypothesis is that the cancer-specific and histology-independent uniform cytokine cascade is one of the manifestations of the underlying paraneoplastic systemic disease, and this hypothesis links the stage of cancer with both the functional status of the immune system and the patient's prognosis. Neutralisation of this cytokine pattern could offer novel and so far unexploited treatment approaches for cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              The Inflammatory Chemokine CCL5 and Cancer Progression

              Until recently, inflammatory chemokines were viewed mainly as indispensable “gate keepers” of immunity and inflammation. However, updated research indicates that cancer cells subvert the normal chemokine system and these molecules and their receptors become important constituents of the tumor microenvironment with very different ways to exert tumor-promoting roles. The CCR5 and the CCL5 ligand have been detected in some hematological malignancies, lymphomas, and a great number of solid tumors, but extensive studies on the role of the CCL5/CCR axis were performed only in a limited number of cancers. This review summarizes updated information on the role of CCL5 and its receptor CCR5 in cancer cell proliferation, metastasis, and the formation of an immunosuppressive microenvironment and highlights the development of newer therapeutic strategies aimed to inhibit the binding of CCL5 to CCR5, to inhibit CCL5 secretion, or to inhibit the interactions among tumor cells and the microenvironment leading to CCL5 secretion.
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                Author and article information

                Journal
                Postepy Dermatol Alergol
                Postepy Dermatol Alergol
                PDIA
                Advances in Dermatology and Allergology/Postȩpy Dermatologii i Alergologii
                Termedia Publishing House
                1642-395X
                2299-0046
                21 October 2016
                October 2016
                : 33
                : 5
                : 381-385
                Affiliations
                [1 ]Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Gdansk, Poland
                [2 ]Department of Pathology and Experimental Rheumatology, Medical University of Gdansk, Gdansk, Poland
                Author notes
                Address for correspondence: Michal Sobjanek MD, PhD, Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, 7 Debinki St, 80-952 Gdansk, Poland. phone: +48 58 349 25 83, fax: +48 58 349 25 86. e-mail: sobjanek@ 123456wp.pl
                Article
                28507
                10.5114/ada.2016.62846
                5110628
                b64d02d2-6a91-4c00-ba88-a508134f2835
                Copyright: © 2016 Termedia Sp. z o.o.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

                History
                : 14 July 2015
                : 18 September 2015
                Categories
                Original Paper

                monocyte chemo-attractant protein 1,monocyte chemoattractant protein 1,ccl2,regulated upon activation normal t-cell expressed and secreted,rantes,ccl5,gene polymorphism,basal cell carcinoma,bcc

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