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Nicotine and oxidative stress induced exomic variations are concordant and overrepresented in cancer-associated genes
Although the connection between cancer and cigarette smoke is well established, nicotine is not characterized as a carcinogen. Here, we used exome sequencing to identify nicotine and oxidative stress-induced somatic mutations in normal human epithelial cells and its correlation with cancer. We ident...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148099/ https://www.ncbi.nlm.nih.gov/pubmed/24947164 |
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author | Bavarva, Jasmin H. Tae, Hongseok McIver, Lauren Garner, Harold R. |
author_facet | Bavarva, Jasmin H. Tae, Hongseok McIver, Lauren Garner, Harold R. |
author_sort | Bavarva, Jasmin H. |
collection | PubMed |
description | Although the connection between cancer and cigarette smoke is well established, nicotine is not characterized as a carcinogen. Here, we used exome sequencing to identify nicotine and oxidative stress-induced somatic mutations in normal human epithelial cells and its correlation with cancer. We identified over 6,400 SNVs, indels and microsatellites in each of the stress exposed cells relative to the control, of which, 2,159 were consistently observed at all nicotine doses. These included 429 nsSNVs including 158 novel and 79 cancer-associated. Over 80% of consistently nicotine induced variants overlap with variations detected in oxidative stressed cells, indicating that nicotine induced genomic alterations could be mediated through oxidative stress. Nicotine induced mutations were distributed across 1,585 genes, of which 49% were associated with cancer. MUC family genes were among the top mutated genes. Analysis of 591 lung carcinoma tumor exomes from The Cancer Genome Atlas (TCGA) revealed that 20% of non-small-cell lung cancer tumors in smokers have mutations in at least one of the MUC4, MUC6 or MUC12 genes in contrast to only 6% in non-smokers. These results indicate that nicotine induces genomic variations, promotes instability potentially mediated by oxidative stress, implicating nicotine in carcinogenesis, and establishes MUC genes as potential targets. |
format | Online Article Text |
id | pubmed-4148099 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-41480992014-08-29 Nicotine and oxidative stress induced exomic variations are concordant and overrepresented in cancer-associated genes Bavarva, Jasmin H. Tae, Hongseok McIver, Lauren Garner, Harold R. Oncotarget Research Paper Although the connection between cancer and cigarette smoke is well established, nicotine is not characterized as a carcinogen. Here, we used exome sequencing to identify nicotine and oxidative stress-induced somatic mutations in normal human epithelial cells and its correlation with cancer. We identified over 6,400 SNVs, indels and microsatellites in each of the stress exposed cells relative to the control, of which, 2,159 were consistently observed at all nicotine doses. These included 429 nsSNVs including 158 novel and 79 cancer-associated. Over 80% of consistently nicotine induced variants overlap with variations detected in oxidative stressed cells, indicating that nicotine induced genomic alterations could be mediated through oxidative stress. Nicotine induced mutations were distributed across 1,585 genes, of which 49% were associated with cancer. MUC family genes were among the top mutated genes. Analysis of 591 lung carcinoma tumor exomes from The Cancer Genome Atlas (TCGA) revealed that 20% of non-small-cell lung cancer tumors in smokers have mutations in at least one of the MUC4, MUC6 or MUC12 genes in contrast to only 6% in non-smokers. These results indicate that nicotine induces genomic variations, promotes instability potentially mediated by oxidative stress, implicating nicotine in carcinogenesis, and establishes MUC genes as potential targets. Impact Journals LLC 2014-05-28 /pmc/articles/PMC4148099/ /pubmed/24947164 Text en Copyright: © 2014 Bavarva et al. http://creativecommons.org/licenses/by/2.5/ 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. |
spellingShingle | Research Paper Bavarva, Jasmin H. Tae, Hongseok McIver, Lauren Garner, Harold R. Nicotine and oxidative stress induced exomic variations are concordant and overrepresented in cancer-associated genes |
title | Nicotine and oxidative stress induced exomic variations are concordant and overrepresented in cancer-associated genes |
title_full | Nicotine and oxidative stress induced exomic variations are concordant and overrepresented in cancer-associated genes |
title_fullStr | Nicotine and oxidative stress induced exomic variations are concordant and overrepresented in cancer-associated genes |
title_full_unstemmed | Nicotine and oxidative stress induced exomic variations are concordant and overrepresented in cancer-associated genes |
title_short | Nicotine and oxidative stress induced exomic variations are concordant and overrepresented in cancer-associated genes |
title_sort | nicotine and oxidative stress induced exomic variations are concordant and overrepresented in cancer-associated genes |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148099/ https://www.ncbi.nlm.nih.gov/pubmed/24947164 |
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