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      Role of telomere length in human carcinogenesis (Review)

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          Abstract

          Cancer is considered the most important clinical, social and economic issue regarding cause-specific disability-adjusted life years among all human pathologies. Exogenous, endogenous and individual factors, including genetic predisposition, participate in cancer triggering. Telomeres are specific DNA structures positioned at the end of chromosomes and consist of repetitive nucleotide sequences, which, together with shelterin proteins, facilitate the maintenance of chromosome stability, while protecting them from genomic erosion. Even though the connection between telomere status and carcinogenesis has been identified, the absence of a universal or even a cancer-specific trend renders consent even more complex. It is indicative that both short and long telomere lengths have been associated with a high risk of cancer incidence. When evaluating risk associations between cancer and telomere length, a disparity appears to emerge. Even though shorter telomeres have been adopted as a marker of poorer health status and an older biological age, longer telomeres due to increased cell growth potential are associated with the acquirement of cancer-initiating somatic mutations. Therefore, the present review aimed to comprehensively present the multifaceted pattern of telomere length and cancer incidence association.

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          CpG islands and the regulation of transcription.

          Vertebrate CpG islands (CGIs) are short interspersed DNA sequences that deviate significantly from the average genomic pattern by being GC-rich, CpG-rich, and predominantly nonmethylated. Most, perhaps all, CGIs are sites of transcription initiation, including thousands that are remote from currently annotated promoters. Shared DNA sequence features adapt CGIs for promoter function by destabilizing nucleosomes and attracting proteins that create a transcriptionally permissive chromatin state. Silencing of CGI promoters is achieved through dense CpG methylation or polycomb recruitment, again using their distinctive DNA sequence composition. CGIs are therefore generically equipped to influence local chromatin structure and simplify regulation of gene activity.
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            Telomeres and human disease: ageing, cancer and beyond.

            Telomere length and telomerase activity are important factors in the pathobiology of human disease. Age-related diseases and premature ageing syndromes are characterized by short telomeres, which can compromise cell viability, whereas tumour cells can prevent telomere loss by aberrantly upregulating telomerase. Altered functioning of both telomerase and telomere-interacting proteins is present in some human premature ageing syndromes and in cancer, and recent findings indicate that alterations that affect telomeres at the level of chromatin structure might also have a role in human disease. These findings have inspired a number of potential therapeutic strategies that are based on telomerase and telomeres.
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              Current Cancer Epidemiology

              In this brief report, we offer a concise overview on current cancer epidemiology garnered from the official databases of World Health Organization and American Cancer Society and provide recent information on frequency, mortality, and survival expectancy of the 15 leading types of cancers worldwide. Overall, cancer poses the highest clinical, social, and economic burden in terms of cause-specific Disability-Adjusted Life Years (DALYs) among all human diseases. The overall 0–74 years risk of developing cancer is 20.2% (22.4% in men and 18.2% in women, respectively). A total number of 18 million new cases have been diagnosed in 2018, the most frequent of which are lung (2.09 million cases), breast (2.09 million cases), and prostate (1.28 million cases) cancers. Beside sex-specific malignancies, the ratio of frequency between men and women is >1 for all cancers, except thyroid (i.e., 0.30). As concerns mortality, cancer is the second worldwide cause of death (8.97 million deaths) after ischemic heart disease, but will likely become the first in 2060 (~18.63 million deaths). Lung, liver, and stomach are the three most deadly cancers in the general population, while lung and breast cancers are the leading causes of cancer related-mortality in men and women, respectively. Prostate and thyroid cancers have the best prognosis, with 5-year survival ~100%, while esophagus, liver, and especially pancreas cancers have the worst prognosis, typically <20% at 5 years. We hope that this report will provide fertile ground for addressing health-care interventions aimed at preventing, diagnosing, and managing cancer around the world.
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                Author and article information

                Journal
                Int J Oncol
                Int J Oncol
                IJO
                International Journal of Oncology
                D.A. Spandidos
                1019-6439
                1791-2423
                July 2023
                22 May 2023
                22 May 2023
                : 63
                : 1
                : 78
                Affiliations
                [1 ]Laboratory of Toxicology, School of Medicine, University of Crete, 71003 Heraklion
                [2 ]Department of Anatomy, School of Medicine, University of Crete, 71003 Heraklion
                [3 ]Creta InterClinic HHG, 71304 Heraklion
                [4 ]Laboratory of Microbiology, University Hospital of Heraklion, 71500 Heraklion
                [5 ]Department of Medical Oncology, Venizeleion General Hospital of Heraklion, 71409 Heraklion
                [6 ]Department of Spine Surgery and Scoliosis, KAT General Hospital, 14561 Athens
                [7 ]Department of Neonatology and Neonatal Intensive Care Unit (NICU), University Hospital of Heraklion, 71500 Heraklion
                [8 ]Department of Radiation Oncology, University Hospital of Crete, 71110 Heraklion, Greece
                [9 ]Department of Pharmacology, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119146 Moscow, Russia
                [10 ]Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Greece
                [11 ]Laboratory of Histology-Embryology, School of Medicine, University of Crete, 71003 Heraklion, Greece
                Author notes
                Correspondence to: Professor Aristidis Tsatsakis, Laboratory of Toxicology, School of Medicine, University of Crete, Voutes, 71003 Heraklion, Greece, E-mail: tsatsaka@ 123456uoc.gr
                [*]

                Contributed equally

                Article
                ijo-63-1-05526
                10.3892/ijo.2023.5526
                10552730
                37232367
                92b2e072-e262-4428-92c0-5caad9ab8bad
                Copyright: © Tsatsakis et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 08 March 2023
                : 11 May 2023
                Funding
                No funding was received.
                Categories
                Articles

                telomere length,lung cancer,laryngeal cancer,bladder cancer,kidney cancer,non-hodgkin's lymphoma,leukemia,melanoma of the skin,colorectal cancer,liver cancer

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