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      Polymorphism of interleukin-6 -174 G/C (rs1800795) & the corresponding interleukin-6 level as a prognostic marker of cervical cancer

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          Abstract

          Background & objectives:

          Aetiology of cervical cancer (CaCx) is multifactorial. Besides human papillomavirus (HPV) infection, many immunogenetic factors are involved in this complex process. The present study was carried out to investigate one such factor, interleukin-6 (IL-6), a central pro-inflammatory cytokine and a polymorphism at its promoter region -174 G/C (rs1800795) with CaCx.

          Methods:

          HPV-infected women with or without CaCx were enrolled in group I and II, respectively. Another group of uninfected healthy women was also included as group III for comparison. Polymorphism in IL-6-174 G/C and IL-6 levels were analyzed by sequence-specific primer PCR (PCR-SSP) and ELISA, respectively.

          Results:

          Groups I (n=111) and II (n=87) had significantly higher frequency of IL-6-174 GG genotype [odds ratios (OR)=3.9; P<0.001 and OR=3.2; P<0.001, respectively] as compared to group III (n=163). Furthermore, individuals with GG or GC genotypes had high IL-6 levels than those with CC genotypes. IL-6 levels were significantly ( P<0.001) elevated in group I. This was also significantly high in untreated cases as compared to treated ( P<0.05) ones. IL-6 levels of treated group were comparable with groups II and III.

          Interpretation & conclusions:

          Our results suggested a possible association of IL-6-174 GG with CaCx, which was also associated with high IL-6 levels. Decreased levels of IL-6 following treatment indicate its possible prognostic use in CaCx cases.

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          Most cited references30

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          Papillomaviruses and cancer: from basic studies to clinical application.

          Links between human papillomaviruses (HPVs) and cervical cancer were first suspected almost 30 years ago. DNA of specific HPV types has since been found in almost all cervical cancer biopsies. HPV oncogenes that are expressed in these cells are involved in their transformation and immortalization, and are required for the progression towards malignancy. Epidemiological studies have underlined that HPVs are the main aetiological factor for cervical cancer. But how has this knowledge been translated into the clinic to allow the prevention, screening and treatment of cervical cancer?
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            Identification of patterns in biological sequences at the ALGGEN server: PROMO and MALGEN.

            In this paper we present several web-based tools to identify conserved patterns in sequences. In particular we present details on the functionality of PROMO version 2.0, a program for the prediction of transcription factor binding site in a single sequence or in a group of related sequences and, of MALGEN, a tool to visualize sequence correspondences among long DNA sequences. The web tools and associated documentation can be accessed at http://www.lsi.upc.es/~alggen (RESEARCH link).
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              Circulating interleukin-6 predicts survival in patients with metastatic breast cancer.

              Interleukin-6 (IL-6) is a multifunctional cytokine produced by macrophages, T cells, B cells, endothelial cells and tumour cells. Interleukin-6 is able to promote tumour growth by upregulating anti-apoptotic and angiogenic proteins in tumour cells. In murine models it has been demonstrated that antibodies against IL-6 diminish tumour growth. Several reports have highlighted the prognostic importance of IL-6 in e.g., prostate and colon cancer. We addressed prospectively the prognostic significance of serum IL-6 (sIL-6), measured at diagnosis of metastasis, in 96 unselected and consecutive patients with progressive metastatic breast cancer before the initiation of systemic therapy. The median sIL-6 value for the breast cancer population was 6.6 +/- 2.1 pg/ml. Patients with 2 or more metastatic sites had higher sIL-6 values compared to those with only 1 metastatic site (respectively 8.15 +/- 1.7 pg/ml and 3.06 +/- 6.6 pg/ml; p < 0.001). Patients with liver metastasis (8.3 +/- 2.4 pg/ml), with pleural effusions (10.65 +/- 9.9 pg/ml) and with dominant visceral disease (8.15 +/- 3.3 pg/ml) had significantly higher values compared to those without liver metastases (4.5 +/- 3.4 pg/ml; p = 0.001), without pleural effusions (5.45 +/- 1.5 pg/ml; p = 0.0077) and with dominant bone disease (4.5 +/- 1.4 pg/ml; p = 0.007) respectively. No correlation between sIL-6 and age, menopausal status, performance status, tumour grade, body-mass index, histology and hormone receptor status was found. Multivariate analysis showed that high levels of serum IL-6 have independent prognostic value. We conclude that circulating IL-6 is associated with worse survival in patients with metastatic breast cancer and is correlated with the extent of disease. Copyright 2002 Wiley-Liss, Inc.
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                Author and article information

                Journal
                Indian J Med Res
                Indian J Med Res
                IJMR
                Indian J Med Res
                The Indian Journal of Medical Research
                Wolters Kluwer - Medknow (India )
                0971-5916
                0975-9174
                August 2021
                August 2021
                : 154
                : 2
                : 391-398
                Affiliations
                [1 ] Department of Infectious Diseases Biology, ICMR-National Institute for Research in Reproductive Health, Mumbai, Maharashtra, India
                [2 ] Department of Surgery, Tata Memorial Hospital, Mumbai, Maharashtra, India
                [3 ] Department of Obstetrics & Gynaecology, King Edward Memorial Hospital & Seth G.S. Medical College, Mumbai, Maharashtra, India
                Author notes
                For correspondence: Dr Jayanti Mania-Pramanik, ICMR- National Institute for Research in Reproductive Health, Mumbai 400 012, Maharashtra, India e-mail: pramanikj@ 123456nirrh.res.in
                Article
                IJMR-154-391
                10.4103/ijmr.IJMR_1111_19
                9131768
                34854425
                3237ab59-4273-4a1d-be8b-527733136a36
                Copyright: © 2022 Indian Journal of Medical Research

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 08 August 2019
                Categories
                Original Article

                Medicine
                cervical cancer,human papillomavirus,interleukin-6,prognostic marker,serum interleukin-6,single-nucleotide polymorphism

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