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Contribution of Environment and Genetics to Pancreatic Cancer Susceptibility
Several risk factors have been identified as potential contributors to pancreatic cancer development, including environmental and lifestyle factors, such as smoking, drinking and diet, and medical conditions such as diabetes and pancreatitis, all of which generate oxidative stress and DNA damage. Ox...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961224/ https://www.ncbi.nlm.nih.gov/pubmed/24651674 http://dx.doi.org/10.1371/journal.pone.0090052 |
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author | Hocevar, Barbara A. Kamendulis, Lisa M. Pu, Xinzhu Perkins, Susan M. Wang, Zheng-Yu Johnston, Erica L. DeWitt, John M. Li, Lang Loehrer, Patrick J. Klaunig, James E. Chiorean, E. Gabriela |
author_facet | Hocevar, Barbara A. Kamendulis, Lisa M. Pu, Xinzhu Perkins, Susan M. Wang, Zheng-Yu Johnston, Erica L. DeWitt, John M. Li, Lang Loehrer, Patrick J. Klaunig, James E. Chiorean, E. Gabriela |
author_sort | Hocevar, Barbara A. |
collection | PubMed |
description | Several risk factors have been identified as potential contributors to pancreatic cancer development, including environmental and lifestyle factors, such as smoking, drinking and diet, and medical conditions such as diabetes and pancreatitis, all of which generate oxidative stress and DNA damage. Oxidative stress status can be modified by environmental factors and also by an individual's unique genetic makeup. Here we examined the contribution of environment and genetics to an individual's level of oxidative stress, DNA damage and susceptibility to pancreatic cancer in a pilot study using three groups of subjects: a newly diagnosed pancreatic cancer group, a healthy genetically-unrelated control group living with the case subject, and a healthy genetically-related control group which does not reside with the subject. Oxidative stress and DNA damage was evaluated by measuring total antioxidant capacity, direct and oxidative DNA damage by Comet assay, and malondialdehyde levels. Direct DNA damage was significantly elevated in pancreatic cancer patients (age and sex adjusted mean ± standard error: 1.00±0.05) versus both healthy unrelated and related controls (0.70±0.06, p<0.001 and 0.82±0.07, p = 0.046, respectively). Analysis of 22 selected SNPs in oxidative stress and DNA damage genes revealed that CYP2A6 L160H was associated with pancreatic cancer. In addition, DNA damage was found to be associated with TNFA −308G>A and ERCC4 R415Q polymorphisms. These results suggest that measurement of DNA damage, as well as select SNPs, may provide an important screening tool to identify individuals at risk for development of pancreatic cancer. |
format | Online Article Text |
id | pubmed-3961224 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39612242014-03-27 Contribution of Environment and Genetics to Pancreatic Cancer Susceptibility Hocevar, Barbara A. Kamendulis, Lisa M. Pu, Xinzhu Perkins, Susan M. Wang, Zheng-Yu Johnston, Erica L. DeWitt, John M. Li, Lang Loehrer, Patrick J. Klaunig, James E. Chiorean, E. Gabriela PLoS One Research Article Several risk factors have been identified as potential contributors to pancreatic cancer development, including environmental and lifestyle factors, such as smoking, drinking and diet, and medical conditions such as diabetes and pancreatitis, all of which generate oxidative stress and DNA damage. Oxidative stress status can be modified by environmental factors and also by an individual's unique genetic makeup. Here we examined the contribution of environment and genetics to an individual's level of oxidative stress, DNA damage and susceptibility to pancreatic cancer in a pilot study using three groups of subjects: a newly diagnosed pancreatic cancer group, a healthy genetically-unrelated control group living with the case subject, and a healthy genetically-related control group which does not reside with the subject. Oxidative stress and DNA damage was evaluated by measuring total antioxidant capacity, direct and oxidative DNA damage by Comet assay, and malondialdehyde levels. Direct DNA damage was significantly elevated in pancreatic cancer patients (age and sex adjusted mean ± standard error: 1.00±0.05) versus both healthy unrelated and related controls (0.70±0.06, p<0.001 and 0.82±0.07, p = 0.046, respectively). Analysis of 22 selected SNPs in oxidative stress and DNA damage genes revealed that CYP2A6 L160H was associated with pancreatic cancer. In addition, DNA damage was found to be associated with TNFA −308G>A and ERCC4 R415Q polymorphisms. These results suggest that measurement of DNA damage, as well as select SNPs, may provide an important screening tool to identify individuals at risk for development of pancreatic cancer. Public Library of Science 2014-03-20 /pmc/articles/PMC3961224/ /pubmed/24651674 http://dx.doi.org/10.1371/journal.pone.0090052 Text en © 2014 Hocevar et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Hocevar, Barbara A. Kamendulis, Lisa M. Pu, Xinzhu Perkins, Susan M. Wang, Zheng-Yu Johnston, Erica L. DeWitt, John M. Li, Lang Loehrer, Patrick J. Klaunig, James E. Chiorean, E. Gabriela Contribution of Environment and Genetics to Pancreatic Cancer Susceptibility |
title | Contribution of Environment and Genetics to Pancreatic Cancer Susceptibility |
title_full | Contribution of Environment and Genetics to Pancreatic Cancer Susceptibility |
title_fullStr | Contribution of Environment and Genetics to Pancreatic Cancer Susceptibility |
title_full_unstemmed | Contribution of Environment and Genetics to Pancreatic Cancer Susceptibility |
title_short | Contribution of Environment and Genetics to Pancreatic Cancer Susceptibility |
title_sort | contribution of environment and genetics to pancreatic cancer susceptibility |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961224/ https://www.ncbi.nlm.nih.gov/pubmed/24651674 http://dx.doi.org/10.1371/journal.pone.0090052 |
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