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      Role of Nitrative and Oxidative DNA Damage in Inflammation-Related Carcinogenesis

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          Abstract

          Chronic inflammation induced by biological, chemical, and physical factors has been found to be associated with the increased risk of cancer in various organs. We revealed that infectious agents including liver fluke, Helicobacter pylori, and human papilloma virus and noninfectious agents such as asbestos fiber induced iNOS-dependent formation of 8-nitroguanine and 8-oxo-7, 8-dihydro-2′-deoxyguanosine (8-oxodG) in cancer tissues and precancerous regions. Our results with the colocalization of phosphorylated ATM and γ-H2AX with 8-oxodG and 8-nitroguanine in inflammation-related cancer tissues suggest that DNA base damage leads to double-stranded breaks. It is interesting from the aspect of genetic instability. We also demonstrated IL-6-modulated iNOS expression via STAT3 and EGFR in Epstein-Barr-virus-associated nasopharyngeal carcinoma and found promoter hypermethylation in several tumor suppressor genes. Such epigenetic alteration may occur by controlling the DNA methylation through IL-6-mediated JAK/STAT3 pathways. Collectively, 8-nitroguanine would be a useful biomarker for predicting the risk of inflammation-related cancers.

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          Most cited references118

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          Cancer statistics, 2004.

          Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival rates based on incidence data from the National Cancer Institute and mortality data from the National Center for Health Statistics. Incidence and mortality rates are age standardized to the 2000 US standard million population. A total of 1,368,030 new cancer cases and 563,700 deaths are expected in the United States in 2004. Incidence rates stabilized among men from 1995 through 2000 but continued to increase among females by 0.4% per year from 1987 through 2000. Mortality rates have decreased by 1.5% per year since 1992 among men, but have stabilized from 1998 through 2000 among women. Cancer death rates continued to decrease from the three major cancer sites in men (lung and bronchus, colon and rectum, and prostate) and from female breast and colorectal cancers in women. In analyses by race and ethnicity, African-American men and women have 40% and 20% higher death rates from all cancers combined compared with White men and women, respectively. Cancer incidence and mortality rates are lower in other racial and ethnic groups than in Whites and African Americans for all sites combined and for the four major cancer sites. However, these groups generally have higher rates for stomach, liver, and cervical cancers than do Whites. Furthermore, minority populations are more likely to be diagnosed with advanced stage disease than are Whites. Progress in reducing the burden from cancer can be accelerated by applying existing cancer control knowledge into practice among all segments of the population.
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            Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States.

            T. Patel (2001)
            Clinical observations suggest a recent increase in intrahepatic biliary tract malignancies. Thus, our aim was to determine recent trends in the epidemiology of intrahepatic cholangiocarcinoma in the United States. Reported data from the Surveillance, Epidemiology, and End Results (SEER) program and the United States Vital Statistics databases were analyzed to determine the incidence, mortality, and survival rates of primary intrahepatic cholangiocarcinoma. Between 1973 and 1997, the incidence and mortality rates from intrahepatic cholangiocarcinoma markedly increased, with an estimated annual percent change (EAPC) of 9.11% (95% CI, 7.46 to 10.78) and 9.44% (95%, CI 8.46 to 10.41), respectively. The age-adjusted mortality rate per 100,000 persons for whites increased from 0.14 for the period 1975-1979 to 0.65 for the period 1993-1997, and that for blacks increased from 0.15 to 0.58 over the same period. The increase in mortality was similar across all age groups above age 45. The relative 1- and 2-year survival rates following diagnosis from 1989 to 1996 were 24.5% and 12.8%, respectively. In conclusion, there has been a marked increase in the incidence and mortality from intrahepatic cholangiocarcinoma in the United States in recent years. This tumor continues to be associated with a poor prognosis.
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              Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA.

              Spontaneous oxidation of guanine residues in DNA generates 8-oxoguanine (oxoG). By mispairing with adenine during replication, oxoG gives rise to a G x C --> T x A transversion, a frequent somatic mutation in human cancers. The dedicated repair pathway for oxoG centres on 8-oxoguanine DNA glycosylase (hOGG1), an enzyme that recognizes oxoG x C base pairs, catalysing expulsion of the oxoG and cleavage of the DNA backbone. Here we report the X-ray structure of the catalytic core of hOGG1 bound to oxoG x C-containing DNA at 2.1 A resolution. The structure reveals the mechanistic basis for the recognition and catalytic excision of DNA damage by hOGG1 and by other members of the enzyme superfamily to which it belongs. The structure also provides a rationale for the biochemical effects of inactivating mutations and polymorphisms in hOGG1. One known mutation, R154H, converts hOGG1 to a promutator by relaxing the specificity of the enzyme for the base opposite oxoG.
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                Author and article information

                Journal
                J Biomed Biotechnol
                J. Biomed. Biotechnol
                JBB
                Journal of Biomedicine and Biotechnology
                Hindawi Publishing Corporation
                1110-7243
                1110-7251
                2012
                26 January 2012
                : 2012
                : 623019
                Affiliations
                1Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, 514-8507, Japan
                2Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, 513-8670, Japan
                3Faculty of Health Science, Suzuka University of Medical Science, Suzuka, 510-0293, Japan
                Author notes

                Academic Editor: Vassilis Gorgoulis

                Article
                10.1155/2012/623019
                3272848
                22363173
                830e3569-251c-451a-9f5b-52e344029035
                Copyright © 2012 Mariko Murata 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.

                History
                : 28 July 2011
                : 7 October 2011
                Categories
                Review Article

                Molecular medicine
                Molecular medicine

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