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Cervical Carcinogenesis and Immune Response Gene Polymorphisms: A Review

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      Abstract

      The local immune response is considered a key determinant in cervical carcinogenesis after persistent infection with oncogenic, high-risk human papillomavirus (HPV) infections. Genetic variation in various immune response genes has been shown to influence risk of developing cervical cancer, as well as progression and survival among cervical cancer patients. We reviewed the literature on associations of immunogenetic single nucleotide polymorphism, allele, genotype, and haplotype distributions with risk and progression of cervical cancer. Studies on HLA and KIR gene polymorphisms were excluded due to the abundance on literature on that subject. We show that multiple genes and loci are associated with variation in risk of cervical cancer. Rather than one single gene being responsible for cervical carcinogenesis, we postulate that variations in the different immune response genes lead to subtle differences in the effectiveness of the antiviral and antitumour immune responses, ultimately leading to differences in risk of developing cervical cancer and progressive disease after HPV infection.

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      Most cited references 121

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          A single mouse click on the topic tumor necrosis factor (TNF) in PubMed reveals about 50,000 articles providing one or the other information about this pleiotropic cytokine or its relatives. This demonstrates the enormous scientific and clinical interest in elucidating the biology of a molecule (or rather a large family of molecules), which began now almost 30 years ago with the description of a cytokine able to exert antitumoral effects in mouse models. Although our understanding of the multiple functions of TNF in vivo and of the respective underlying mechanisms at a cellular and molecular level has made enormous progress since then, new aspects are steadily uncovered and it appears that still much needs to be learned before we can conclude that we have a full comprehension of TNF biology. This review shortly covers some general aspects of this fascinating molecule and then concentrates on the molecular mechanisms of TNF signal transduction. In particular, the multiple facets of crosstalk between the various signalling pathways engaged by TNF will be addressed.
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            Author and article information

            Affiliations
            1Department of Pathology, Leiden University Medical Centre, Leiden, Netherlands
            2Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Centre, Amsterdam, Netherlands
            3Institute for Public Health Genomics, Department of Genetics and Cell Biology, School for Oncology and Developmental Biology (GROW), Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
            4Centre for Gynaecological Oncology Amsterdam, Amsterdam, Netherlands
            Author notes
            *Ekaterina S. Jordanova: e.jordanova@ 123456lumc.nl

            Academic Editor: Margarete D. Bagatini

            Journal
            J Immunol Res
            J Immunol Res
            JIR
            Journal of Immunology Research
            Hindawi Publishing Corporation
            2314-8861
            2314-7156
            2017
            9 February 2017
            : 2017
            5322437
            10.1155/2017/8913860
            Copyright © 2017 Akash M. Mehta et al.

            This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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