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      Neutrophil to lymphocyte ratio and breast cancer risk: analysis by subtype and potential interactions

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          Abstract

          Multiple studies have found the neutrophil to lymphocyte ratio (NLR) to be associated with adverse breast cancer (BC) prognosis and survival. Very limited data exist on the role of NLR and risk of BC. The BREOGAN study is a population-based case–control study conducted in Galicia, Spain. We examined the WBC- and NLR-BC relationships. The risk of BC increased with increasing levels of neutrophils percentage (NE%) (multivariable OR for the highest category (95% CI) = 2.14 (1.39–3.32), P-trend < 0.001) and of the NLR (multivariable OR for the highest category (95% CI) = 1.93 (1.26–2.97), P-trend < 0.001). Lymphocytes absolute (L#) and percentage (L%) were associated with a decreased risk of BC (multivariable OR for the highest category (95% CI) = 0.54 (0.35–0.83), and 0.51 (0.33–0.79), P-trend = 0.001 and < 0.001, respectively). The NLR-BC association was more pronounced among Luminal A BC (multivariable OR for the highest category (95% CI) = 2.00 (1.17–3.45), P-trend < 0.001), HER2-negative BC (multivariable OR for the highest category (95% CI) = 1.87 (1.16–3.02), P-trend < 0.001), and those with high total cholesterol and low H 2O 2 levels.

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          Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions.

          Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue's homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to "bad luck," that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes. Copyright © 2015, American Association for the Advancement of Science.
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            Role of reactive oxygen species (ROS) in apoptosis induction.

            Reactive oxygen species (ROS) and mitochondria play an important role in apoptosis induction under both physiologic and pathologic conditions. Interestingly, mitochondria are both source and target of ROS. Cytochrome c release from mitochondria, that triggers caspase activation, appears to be largely mediated by direct or indirect ROS action. On the other hand, ROS have also anti-apoptotic effects. This review focuses on the role of ROS in the regulation of apoptosis, especially in inflammatory cells.
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              The neutrophil-to-lymphocyte ratio: a narrative review

              Cellular-mediated inflammatory response, lymphocytes, neutrophils, and monocytes are increasingly being recognised as having an important role in tumorigenesis and carcinogenesis. In this context, studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) can be used as an independent prognostic factor in a variety of cancers. Particularly in breast cancer, several studies have shown that a high NLR is associated with shorter survival. Because the NLR can be easily determined from the full blood count, it could potentially provide a simple and inexpensive test cancer prognosis. This review addresses the possibilities and limitations of using the NLR as a clinical tool for risk stratification helpful for individual treatment of breast cancer patients. The potential underlying phenomena and some perspectives are discussed.
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                Author and article information

                Contributors
                manuela.gago.dominguez@sergas.es
                marcos.matabuena@usc.es
                carmen.redondo.marey@sergas.es
                patel@ucsd.edu
                angel.carracedo@usc.es
                sara.miranda.ponte@sergas.es
                e8martinez@ucsd.edu
                jose.esteban.castelao.fernandez@sergas.es
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                6 August 2020
                6 August 2020
                2020
                : 10
                : 13203
                Affiliations
                [1 ]GRID grid.488911.d, ISNI 0000 0004 0408 4897, Galician Public Foundation of Genomic Medicine (FPGMX), Genomic Medicine Group, International Cancer Genetics and Epidemiology Group, , Health Research Institute of Santiago (IDIS), ; Santiago de Compostela, Spain
                [2 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Moores Cancer Center, , University of California San Diego, ; La Jolla, CA USA
                [3 ]GRID grid.11794.3a, ISNI 0000000109410645, Centro de Investigación en Tecnoloxías da Información (CITIUS), , Universidade de Santiago de Compostela, ; Santiago de Compostela, Spain
                [4 ]Oncology and Genetics Unit, Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain
                [5 ]GRID grid.11794.3a, ISNI 0000000109410645, Forensic Department, , Universidade de Santiago de Compostela, ; Santiago de Compostela, Spain
                [6 ]GRID grid.266100.3, ISNI 0000 0001 2107 4242, Department of Family Medicine and Public Health, , University of California San Diego, ; La Jolla, CA USA
                Author information
                http://orcid.org/0000-0002-8387-4840
                Article
                70077
                10.1038/s41598-020-70077-z
                7413522
                32764699
                6a802138-1da0-4f67-ad1c-85dbbff08e29
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 July 2019
                : 21 July 2020
                Funding
                Funded by: FundRef 501100004587, Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III);
                Award ID: PI12/02125
                Award ID: PI17/00918
                Funded by: FundRef 501100010556, Consellería de Economía, Emprego e Industria, Xunta de Galicia (Consellea de Economía e Industria, Xunta de Galicia);
                Award ID: 10CSA012E
                Funded by: FundRef 501100003751, Ministerio de Sanidad, Servicios Sociales e Igualdad (Ministry of Health, Social Services and Equality);
                Award ID: EC11-192
                Funded by: Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
                Award ID: PI13/01136
                Award ID: PI12/02125
                Award ID: PI17/00918
                Funded by: Ministerio de Economía y Competitividad y Consellería de Cultura, Educación e Ordenación Universitaria, Spain and the European Regional Development Fund (ERDF). Grant FEDER-Innterconecta. Accreditation 2016-2019, Programa Grupos Emergentes, Cancer Genetics Unit, CHUVI, Vigo Hospital, Instituto de Salud Carlos III, Spain
                Award ID: ED431G/08
                Funded by: FundRef 100002491, Bristol-Myers Squibb (Bristol-Myers Squibb Company);
                Funded by: FundRef 100004312, Eli Lilly and Company (Lilly);
                Funded by: FundRef 501100004628, MedImmune;
                Funded by: FundRef 100004334, Merck (Merck and Co., Inc.);
                Funded by: FundRef 100004319, Pfizer (Pfizer Inc.);
                Funded by: FundRef 100004328, Genentech (Genentech, Inc.);
                Funded by: Fate,Fate Therapeutics, Incyte, AstraZeneca, Roche, Xcovery, Genocea, Iovance
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                lipidomics,breast cancer,biomarkers
                Uncategorized
                lipidomics, breast cancer, biomarkers

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