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      Human papilloma virus and breast cancer: the role of inflammation and viral expressed proteins

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          Abstract

          Background

          Breast cancer is currently the most common neoplasm diagnosed in women globally. There is a growing body of evidence to suggest that human papillomavirus (HPV) infection may play a key role in invasiveness of breast cancer. The aim of this study was to determine the presence of HPV in patients with breast cancer and its possible association with cancer progression.

          Methods

          Breast specimens were collected from 72 patients with breast cancer and 31 healthy controls. The presence of HPV was investigated by polymerase chain reaction (PCR) and genotyping was performed for positive cases. We also evaluated the viral factors such as E6, E2, and E7 in HPV positive cases. Enzyme-linked immunosorbent assay (ELISA (and Real-time PCR techniques were used to measure the expression level of anti-carcinogenic genes, such as p53, retinoblastoma ( RB), breast and ovarian cancer susceptibility gene ( BRCA1, BRCA2) and inflammatory cytokines, including tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β), nuclear factor-kB (NF-kB), and different interleukins [ILs] (IL-1,IL6, and IL-17).

          Results

          The HPV DNA was detected in 48.6% of breast cancer samples, whereas only 16.1% of controls were positive for HPV. We observed statistically significant differences between breast cancer patients and HPV presence ( P = 0.003). HPV type 18 was the most prevalent virus genotype in patients. The expression of P53, RB, BRCA1, and BRCA2 were decreased in patients with HPV-positive breast cancer as compared to HPV-negative breast cancer and healthy controls. (All P-values were less than 0.05). The presence of the HPV was associated with increased inflammatory cytokines (IL-1, IL-6, IL-17, TGF-β, TNF-α, and NF-kB) and tumor progression.

          Conclusion

          The present study demonstrated that HPV infection may implicate in the development of some types of breast cancer.

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          Most cited references65

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          Inflammation and cancer.

          Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.
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            Global Cancer Statistics, 2002

            Estimates of the worldwide incidence, mortality and prevalence of 26 cancers in the year 2002 are now available in the GLOBOCAN series of the International Agency for Research on Cancer. The results are presented here in summary form, including the geographic variation between 20 large "areas" of the world. Overall, there were 10.9 million new cases, 6.7 million deaths, and 24.6 million persons alive with cancer (within three years of diagnosis). The most commonly diagnosed cancers are lung (1.35 million), breast (1.15 million), and colorectal (1 million); the most common causes of cancer death are lung cancer (1.18 million deaths), stomach cancer (700,000 deaths), and liver cancer (598,000 deaths). The most prevalent cancer in the world is breast cancer (4.4 million survivors up to 5 years following diagnosis). There are striking variations in the risk of different cancers by geographic area. Most of the international variation is due to exposure to known or suspected risk factors related to lifestyle or environment, and provides a clear challenge to prevention.
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              Inflammation in prostate carcinogenesis.

              About 20% of all human cancers are caused by chronic infection or chronic inflammatory states. Recently, a new hypothesis has been proposed for prostate carcinogenesis. It proposes that exposure to environmental factors such as infectious agents and dietary carcinogens, and hormonal imbalances lead to injury of the prostate and to the development of chronic inflammation and regenerative 'risk factor' lesions, referred to as proliferative inflammatory atrophy (PIA). By developing new experimental animal models coupled with classical epidemiological studies, genetic epidemiological studies and molecular pathological approaches, we should be able to determine whether prostate cancer is driven by inflammation, and if so, to develop new strategies to prevent the disease.
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                Author and article information

                Contributors
                nkh2333@yahoo.com
                shayanmostafaee@yahoo.com
                etemadiashkan68@yahoo.com
                ghasemi.mse@gmail.com
                md.payandeh@yahoo.com
                shima_hadifar@yahoo.com
                norooznezhad@gmail.com
                Kazemnejad_an@modares.ac.ir
                +98-8334622427 , mohsenmoghoofei@yahoo.com
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                14 January 2019
                14 January 2019
                2019
                : 19
                : 61
                Affiliations
                [1 ]ISNI 0000 0004 4911 7066, GRID grid.411746.1, Department of Internal Medicine, Faculty of Medicine, , Iran University of Medical Sciences, ; Tehran, Iran
                [2 ]ISNI 0000 0001 0166 0922, GRID grid.411705.6, Department of Community Medicine, Faculty of Medicine, , Alborz University of Medical Sciences, ; Tehran, Iran
                [3 ]ISNI 0000 0001 1781 3962, GRID grid.412266.5, Department of Biostatistics, Faculty of Medical Sciences, , Tarbiat Modares University, ; Tehran, Iran
                [4 ]ISNI 0000 0004 0382 5622, GRID grid.440800.8, Department of Biology, Faculty of Science, , Shahrekord University, ; Shahrekord, Iran
                [5 ]ISNI 0000 0001 0740 9747, GRID grid.412553.4, Department of Materials Science and Engineering, , Sharif University of Technology, ; Tehran, Iran
                [6 ]ISNI 0000 0001 2012 5829, GRID grid.412112.5, Cancer Research Center, , Kermanshah University of Medical Sciences, ; Kermanshah, Iran
                [7 ]ISNI 0000 0000 9562 2611, GRID grid.420169.8, Department of Mycobacteriology & Pulmonary Research, , Pasteur Institute of Iran, ; Tehran, Iran
                [8 ]ISNI 0000 0001 2012 5829, GRID grid.412112.5, Regenerative Medicine Research Center, , Kermanshah University of Medical Sciences, ; Kermanshah, Iran
                [9 ]ISNI 0000 0001 2012 5829, GRID grid.412112.5, Department of Microbiology, Faculty of Medicine, , Kermanshah University of Medical Sciences, ; Sorkheh-Ligeh Blvd, P. O. Box: 6716777816, Kermanshah, Iran
                Article
                5286
                10.1186/s12885-019-5286-0
                6332859
                30642295
                d5f72640-6a1e-4da5-9280-43069cacb520
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 1 November 2017
                : 7 January 2019
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Oncology & Radiotherapy
                breast cancer,human papilloma virus,risk factor,tumor development,inflammation

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