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      Association of Betel Nut with Carcinogenesis: Revisit with a Clinical Perspective

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          Abstract

          Betel nut (BN), betel quid (BQ) and products derived from them are widely used as a socially endorsed masticatory product. The addictive nature of BN/BQ has resulted in its widespread usage making it the fourth most abused substance by humans. Progressively, several additives, including chewing tobacco, got added to simple BN preparations. This addictive practice has been shown to have strong etiological correlation with human susceptibility to cancer, particularly oral and oropharyngeal cancers.

          The PUBMED database was searched to retrieve all relevant published studies in English on BN and BQ, and its association with oral and oropharyngeal cancers. Only complete studies directly dealing with BN/BQ induced carcinogenesis using statistically valid and acceptable sample size were analyzed. Additional relevant information available from other sources was also considered.

          This systematic review attempts to put in perspective the consequences of this widespread habit of BN/BQ mastication, practiced by approximately 10% of the world population, on oral cancer with a clinical perspective. BN/BQ mastication seems to be significantly associated with susceptibility to oral and oropharyngeal cancers. Addition of tobacco to BN has been found to only marginally increase the cancer risk. Despite the widespread usage of BN/BQ and its strong association with human susceptibility to cancer, no serious strategy seems to exist to control this habit. The review, therefore, also looks at various preventive efforts being made by governments and highlights the multifaceted intervention strategies required to mitigate and/or control the habit of BN/BQ mastication.

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          Most cited references136

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          p53 mutations in human cancers.

          Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues. Analysis of these mutations can provide clues to the etiology of these diverse tumors and to the function of specific regions of p53. Transitions predominate in colon, brain, and lymphoid malignancies, whereas G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung and liver. Mutations at A:T base pairs are seen more frequently in esophageal carcinomas than in other solid tumors. Most transitions in colorectal carcinomas, brain tumors, leukemias, and lymphomas are at CpG dinucleotide mutational hot spots. G to T transversions in lung, breast, and esophageal carcinomas are dispersed among numerous codons. In liver tumors in persons from geographic areas in which both aflatoxin B1 and hepatitis B virus are cancer risk factors, most mutations are at one nucleotide pair of codon 249. These differences may reflect the etiological contributions of both exogenous and endogenous factors to human carcinogenesis.
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            Tannins and human health: a review.

            Tannins (commonly referred to as tannic acid) are water-soluble polyphenols that are present in many plant foods. They have been reported to be responsible for decreases in feed intake, growth rate, feed efficiency, net metabolizable energy, and protein digestibility in experimental animals. Therefore, foods rich in tannins are considered to be of low nutritional value. However, recent findings indicate that the major effect of tannins was not due to their inhibition on food consumption or digestion but rather the decreased efficiency in converting the absorbed nutrients to new body substances. Incidences of certain cancers, such as esophageal cancer, have been reported to be related to consumption of tannins-rich foods such as betel nuts and herbal teas, suggesting that tannins might be carcinogenic. However, other reports indicated that the carcinogenic activity of tannins might be related to components associated with tannins rather than tannins themselves. Interestingly, many reports indicated negative association between tea consumption and incidences of cancers. Tea polyphenols and many tannin components were suggested to be anticarcinogenic. Many tannin molecules have also been shown to reduce the mutagenic activity of a number of mutagens. Many carcinogens and/or mutagens produce oxygen-free radicals for interaction with cellular macromolecules. The anticarcinogenic and antimutagenic potentials of tannins may be related to their antioxidative property, which is important in protecting cellular oxidative damage, including lipid peroxidation. The generation of superoxide radicals was reported to be inhibited by tannins and related compounds. The antimicrobial activities of tannins are well documented. The growth of many fungi, yeasts, bacteria, and viruses was inhibited by tannins. We have also found that tannic acid and propyl gallate, but not gallic acid, were inhibitory to foodborne bacteria, aquatic bacteria, and off-flavor-producing microorganisms. Their antimicrobial properties seemed to be associated with the hydrolysis of ester linkage between gallic acid and polyols hydrolyzed after ripening of many edible fruits. Tannins in these fruits thus serve as a natural defense mechanism against microbial infections. The antimicrobial property of tannic acid can also be used in food processing to increase the shelf-life of certain foods, such as catfish fillets. Tannins have also been reported to exert other physiological effects, such as to accelerate blood clotting, reduce blood pressure, decrease the serum lipid level, produce liver necrosis, and modulate immunoresponses. The dosage and kind of tannins are critical to these effects. The aim of this review is to summarize and analyze the vast and sometimes conflicting literature on tannins and to provide as accurately as possible the needed information for assessment of the overall effects of tannins on human health.
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              Clinical implications of the p53 tumor-suppressor gene.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                13 August 2012
                : 7
                : 8
                : e42759
                Affiliations
                [1 ]Radiation and Molecular Biology Unit, Department of Biochemistry, North-Eastern Hill University, Shillong, Meghalaya, India
                [2 ]Division of Cytopathology, Center for Oral Cancer and Precancer, Moti Lal Nehru Medical College, Allahabad, Uttar Pradesh, India
                [3 ]Department of Biotechnology, Assam University, Silchar, Assam, India
                [4 ]Ganeshiva Consultants, Los Angeles, California, United States of America
                Ohio State University, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Article
                PONE-D-12-10391
                10.1371/journal.pone.0042759
                3418282
                22912735
                e3183b51-37a7-42b5-8786-fad0e1205251
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 5 April 2012
                : 11 July 2012
                Page count
                Pages: 1
                Funding
                Part funding from North Eastern Hill University, UPE (NEHU) and DST, which where utilized for some of the works mentioned in the manuscript, are acknowledged. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Molecular Cell Biology
                Cellular Stress Responses
                Toxicology
                Genetic Toxicology
                Toxic Agents
                Medicine
                Clinical Research Design
                Systematic Reviews
                Drugs and Devices
                Behavioral Pharmacology
                Recreational Drug Use
                Epidemiology
                Cancer Epidemiology
                Environmental Epidemiology
                Social Epidemiology
                Gastroenterology and Hepatology
                Gastrointestinal Cancers
                Global Health
                Mental Health
                Psychiatry
                Substance Abuse
                Oncology
                Cancer Risk Factors
                Lifestyle Causes of Cancer
                Nutritional Correlates of Cancer
                Cancers and Neoplasms
                Skin Tumors
                Oral Mucosal Cancers
                Gastrointestinal Tumors
                Cancer Prevention
                Oral Medicine
                Oral Diseases
                Otorhinolaryngology
                Head and Neck Cancers
                Public Health
                Behavioral and Social Aspects of Health

                Uncategorized
                Uncategorized

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