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Correlation between Base-Excision Repair Gene Polymorphisms and Levels of In-Vitro BPDE–Induced DNA Adducts in Cultured Peripheral Blood Lymphocytes
In vitro benzo[a]pyrene diol epoxide (BPDE)-induced DNA adducts in cultured peripheral lymphocytes have been shown to be a phenotypic biomarker of individual’s DNA repair phenotype that is associated with cancer risk. In this study, we explored associations between genotypes of base-excision repair...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390316/ https://www.ncbi.nlm.nih.gov/pubmed/22792228 http://dx.doi.org/10.1371/journal.pone.0040131 |
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author | Yu, Hongping Zhao, Hui Wang, Li-E Liu, Zhensheng Li, Donghui Wei, Qingyi |
author_facet | Yu, Hongping Zhao, Hui Wang, Li-E Liu, Zhensheng Li, Donghui Wei, Qingyi |
author_sort | Yu, Hongping |
collection | PubMed |
description | In vitro benzo[a]pyrene diol epoxide (BPDE)-induced DNA adducts in cultured peripheral lymphocytes have been shown to be a phenotypic biomarker of individual’s DNA repair phenotype that is associated with cancer risk. In this study, we explored associations between genotypes of base-excision repair genes (PARP1 Val762Ala, APEX1 Asp148Glu, and XRCC1 Arg399Gln) and in vitro BPDE-induced DNA adducts in cultured peripheral blood lymphocytes in 706 cancer-free non-Hispanic white subjects. We found that levels of BPDE-induced DNA adducts were significantly higher in ever smokers than in never smokers and that individuals with the Glu variant genotypes (i.e., Asp/Glu and Glu/Glu) exhibited lower levels of BPDE-induced DNA adducts than did individuals with the common Asp/Asp homozygous genotype (median RAL levels: 32.0 for Asp/Asp, 27.0 for Asp/Glu, and 17.0 for Glu/Glu, respectively; P (trend) = 0.030). Further stratified analysis showed that compared with individuals with the common APEX1-148 homozygous Asp/Asp genotype, individuals with the APEX1-148Asp/Glu genotype or the Glu/Glu genotype had a lower risk of having higher-level adducts (adjusted OR = 0.60, 95% CI: 0.36–0.98 and adjusted OR = 0.47, 95% CI: 0.26–0.86, respectively; P (trend) = 0.012) among smokers. Such an effect was not observed in non-smokers. However, there was no significant interaction between the APEX1 Asp148Glu polymorphism and smoking exposure in this study population (P = 0.512). Additional genotype-phenotype analysis found that the APEX1-148Glu allele had significantly increased expression of APEX1 mRNA in 270 Epstein-Barr virus-transformed lymphoblastoid cell lines, which is likely associated with more active repair activity. Our findings suggest that the functional APEX1-148Glu allele is associated with reduced risk of having high levels of BPDE-induced DNA adducts mediated with high levels of mRNA expression. |
format | Online Article Text |
id | pubmed-3390316 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33903162012-07-12 Correlation between Base-Excision Repair Gene Polymorphisms and Levels of In-Vitro BPDE–Induced DNA Adducts in Cultured Peripheral Blood Lymphocytes Yu, Hongping Zhao, Hui Wang, Li-E Liu, Zhensheng Li, Donghui Wei, Qingyi PLoS One Research Article In vitro benzo[a]pyrene diol epoxide (BPDE)-induced DNA adducts in cultured peripheral lymphocytes have been shown to be a phenotypic biomarker of individual’s DNA repair phenotype that is associated with cancer risk. In this study, we explored associations between genotypes of base-excision repair genes (PARP1 Val762Ala, APEX1 Asp148Glu, and XRCC1 Arg399Gln) and in vitro BPDE-induced DNA adducts in cultured peripheral blood lymphocytes in 706 cancer-free non-Hispanic white subjects. We found that levels of BPDE-induced DNA adducts were significantly higher in ever smokers than in never smokers and that individuals with the Glu variant genotypes (i.e., Asp/Glu and Glu/Glu) exhibited lower levels of BPDE-induced DNA adducts than did individuals with the common Asp/Asp homozygous genotype (median RAL levels: 32.0 for Asp/Asp, 27.0 for Asp/Glu, and 17.0 for Glu/Glu, respectively; P (trend) = 0.030). Further stratified analysis showed that compared with individuals with the common APEX1-148 homozygous Asp/Asp genotype, individuals with the APEX1-148Asp/Glu genotype or the Glu/Glu genotype had a lower risk of having higher-level adducts (adjusted OR = 0.60, 95% CI: 0.36–0.98 and adjusted OR = 0.47, 95% CI: 0.26–0.86, respectively; P (trend) = 0.012) among smokers. Such an effect was not observed in non-smokers. However, there was no significant interaction between the APEX1 Asp148Glu polymorphism and smoking exposure in this study population (P = 0.512). Additional genotype-phenotype analysis found that the APEX1-148Glu allele had significantly increased expression of APEX1 mRNA in 270 Epstein-Barr virus-transformed lymphoblastoid cell lines, which is likely associated with more active repair activity. Our findings suggest that the functional APEX1-148Glu allele is associated with reduced risk of having high levels of BPDE-induced DNA adducts mediated with high levels of mRNA expression. Public Library of Science 2012-07-05 /pmc/articles/PMC3390316/ /pubmed/22792228 http://dx.doi.org/10.1371/journal.pone.0040131 Text en Yu 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 Yu, Hongping Zhao, Hui Wang, Li-E Liu, Zhensheng Li, Donghui Wei, Qingyi Correlation between Base-Excision Repair Gene Polymorphisms and Levels of In-Vitro BPDE–Induced DNA Adducts in Cultured Peripheral Blood Lymphocytes |
title | Correlation between Base-Excision Repair Gene Polymorphisms and Levels of In-Vitro BPDE–Induced DNA Adducts in Cultured Peripheral Blood Lymphocytes |
title_full | Correlation between Base-Excision Repair Gene Polymorphisms and Levels of In-Vitro BPDE–Induced DNA Adducts in Cultured Peripheral Blood Lymphocytes |
title_fullStr | Correlation between Base-Excision Repair Gene Polymorphisms and Levels of In-Vitro BPDE–Induced DNA Adducts in Cultured Peripheral Blood Lymphocytes |
title_full_unstemmed | Correlation between Base-Excision Repair Gene Polymorphisms and Levels of In-Vitro BPDE–Induced DNA Adducts in Cultured Peripheral Blood Lymphocytes |
title_short | Correlation between Base-Excision Repair Gene Polymorphisms and Levels of In-Vitro BPDE–Induced DNA Adducts in Cultured Peripheral Blood Lymphocytes |
title_sort | correlation between base-excision repair gene polymorphisms and levels of in-vitro bpde–induced dna adducts in cultured peripheral blood lymphocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390316/ https://www.ncbi.nlm.nih.gov/pubmed/22792228 http://dx.doi.org/10.1371/journal.pone.0040131 |
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