Blog
About

14
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Epigenetic, Genetic and Environmental Interactions in Esophageal Squamous Cell Carcinoma from Northeast India

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Esophageal squamous cell carcinoma (ESCC) develops as a result of complex epigenetic, genetic and environmental interactions. Epigenetic changes like, promoter hypermethylation of multiple tumour suppressor genes are frequent events in cancer, and certain habit-related carcinogens are thought to be capable of inducing aberrant methylation. However, the effects of environmental carcinogens depend upon the level of metabolism by carcinogen metabolizing enzymes. As such key interactions between habits related factors and carcinogen metabolizing gene polymorphisms towards modulating promoter methylation of genes are likely. However, this remains largely unexplored in ESCC. Here, we studied the interaction of various habits related factors and polymorphism of GSTM1/ GSTT1 genes towards inducing promoter hypermethylation of multiple tumour suppressor genes.

          Methodology/Principal Findings

          The study included 112 ESCC cases and 130 age and gender matched controls. Conditional logistic regression was used to calculate odds ratios (OR) and multifactor dimensionality reduction (MDR) was used to explore high order interactions. Tobacco chewing and smoking were the major individual risk factors of ESCC after adjusting for all potential confounding factors. With regards to methylation status, significantly higher methylation frequencies were observed in tobacco chewers than non chewers for all the four genes under study (p<0.01). In logistic regression analysis, betel quid chewing, alcohol consumption and null GSTT1 genotypes imparted maximum risk for ESCC without promoter hypermethylation. Whereas, tobacco chewing, smoking and GSTT1 null variants were the most important risk factors for ESCC with promoter hypermethylation. MDR analysis revealed two predictor models for ESCC with promoter hypermethylation (Tobacco chewing/Smoking/Betel quid chewing/ GSTT1 null) and ESCC without promoter hypermethylation (Betel quid chewing/Alcohol/ GSTT1) with TBA of 0.69 and 0.75 respectively and CVC of 10/10 in both models.

          Conclusion

          Our study identified a possible interaction between tobacco consumption and carcinogen metabolizing gene polymorphisms towards modulating promoter methylation of tumour suppressor genes in ESCC.

          Related collections

          Most cited references 39

          • Record: found
          • Abstract: not found
          • Article: not found

          Global cancer statistics

           A Jemal,  F BRAY,  MM Center (2011)
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Global cancer statistics

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Assessing the probability that a positive report is false: an approach for molecular epidemiology studies.

              Too many reports of associations between genetic variants and common cancer sites and other complex diseases are false positives. A major reason for this unfortunate situation is the strategy of declaring statistical significance based on a P value alone, particularly, any P value below.05. The false positive report probability (FPRP), the probability of no true association between a genetic variant and disease given a statistically significant finding, depends not only on the observed P value but also on both the prior probability that the association between the genetic variant and the disease is real and the statistical power of the test. In this commentary, we show how to assess the FPRP and how to use it to decide whether a finding is deserving of attention or "noteworthy." We show how this approach can lead to improvements in the design, analysis, and interpretation of molecular epidemiology studies. Our proposal can help investigators, editors, and readers of research articles to protect themselves from overinterpreting statistically significant findings that are not likely to signify a true association. An FPRP-based criterion for deciding whether to call a finding noteworthy formalizes the process already used informally by investigators--that is, tempering enthusiasm for remarkable study findings with considerations of plausibility.
                Bookmark

                Author and article information

                Affiliations
                Department of Biotechnology, Assam University, Silchar, Assam, India
                Chinese Academy of Medical Sciences, China
                Author notes

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

                Idea: SKG. Experiment: FRT RSL RM. Software analysis: RSL. Design: FRT SKG. Analyzed the data: FRT RSL SKG. Contributed reagents/materials/analysis tools: FRT RSL RM. Wrote the paper: RSL SKG.

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                15 April 2013
                : 8
                : 4
                PONE-D-13-03662
                10.1371/journal.pone.0060996
                3626640
                23596512

                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.

                Counts
                Pages: 12
                Funding
                The authors thank Department of Biotechnology, Government of India for providing infastructural support 380 (DBT grant number- BT/Med/NE-SFC/2009). The authors do not have any Extramural fund 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
                Computational Biology
                Genomics
                Epigenomics
                Genome Analysis Tools
                Population Genetics
                Genetic Polymorphism
                Genetics
                Population Genetics
                Genetic Polymorphism
                Cancer Genetics
                Epigenetics
                Human Genetics
                Population Biology
                Population Genetics
                Genetic Polymorphism
                Medicine
                Epidemiology
                Cancer Epidemiology
                Oncology
                Cancer Risk Factors
                Environmental Causes of Cancer
                Genetic Causes of Cancer
                Lifestyle Causes of Cancer
                Cancers and Neoplasms
                Gastrointestinal Tumors
                Esophageal Cancer
                Cancer Detection and Diagnosis
                Cancer Prevention

                Uncategorized

                Comments

                Comment on this article