Epigenetic, genetic and environmental interactions in esophageal squamous cell carcinoma from northeast India.
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 tho...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3626640?pdf=render |
| _version_ | 1818337288726249472 |
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| author | Fazlur Rahman Talukdar Sankar Kumar Ghosh Ruhina Shirin Laskar Rosy Mondal |
| author_facet | Fazlur Rahman Talukdar Sankar Kumar Ghosh Ruhina Shirin Laskar Rosy Mondal |
| author_sort | Fazlur Rahman Talukdar |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T14:52:50Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a4df29745c6b4018bedde7f5a10515f82022-12-21T23:41:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6099610.1371/journal.pone.0060996Epigenetic, genetic and environmental interactions in esophageal squamous cell carcinoma from northeast India.Fazlur Rahman TalukdarSankar Kumar GhoshRuhina Shirin LaskarRosy MondalBACKGROUND: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.http://europepmc.org/articles/PMC3626640?pdf=render |
| spellingShingle | Fazlur Rahman Talukdar Sankar Kumar Ghosh Ruhina Shirin Laskar Rosy Mondal Epigenetic, genetic and environmental interactions in esophageal squamous cell carcinoma from northeast India. PLoS ONE |
| title | Epigenetic, genetic and environmental interactions in esophageal squamous cell carcinoma from northeast India. |
| title_full | Epigenetic, genetic and environmental interactions in esophageal squamous cell carcinoma from northeast India. |
| title_fullStr | Epigenetic, genetic and environmental interactions in esophageal squamous cell carcinoma from northeast India. |
| title_full_unstemmed | Epigenetic, genetic and environmental interactions in esophageal squamous cell carcinoma from northeast India. |
| title_short | Epigenetic, genetic and environmental interactions in esophageal squamous cell carcinoma from northeast India. |
| title_sort | epigenetic genetic and environmental interactions in esophageal squamous cell carcinoma from northeast india |
| url | http://europepmc.org/articles/PMC3626640?pdf=render |
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