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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Gene-environment interactions between DNA repair polymorphisms and exposure to the carcinogen vinyl chloride
Biomarkers, v 14(3), pp 148-155
01 Jan 2009
PMID: 19274602
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We have recently suggested that polymorphisms in metabolism and repair pathways may play a role in modulating the effects of exposure to the carcinogen vinyl chloride in the production of biomarkers of its mutagenic damage. The aim of the present study was to extend these observations by examining gene-environment interactions between several common polymorphisms in the DNA repair genes XRCC1 and ERCC2/XPD and vinyl chloride exposure on the production of vinyl chloride-induced biomarkers of mutation. A cohort of 546 French vinyl chloride workers were genotyped for the XRCC1 codon 194 (ArgTrp; rs1799782), 280 (ArgHis; rs25489) and 399 (ArgGln; rs25487) polymorphisms and the ERCC2/XPD codon 312 (AspAsn; rs1799793) and 751 (LysGln; rs13181) polymorphisms. The results demonstrated a statistically significant allele dosage effect of the XRCC1 399 variant on the production of the vinyl chloride-induced mutant p53 biomarker, even after controlling for confounders including cumulative vinyl chloride exposure (p = 0.03), with a potentially supramultiplicative gene-environment interaction. In addition, the results demonstrate statistically significant allele dosage effects of the ERCC2/XPD 312 and 751 variants on the production of the vinyl chloride-induced mutant ras-p21 biomarker, even after controlling for confounders including cumulative vinyl chloride exposure (p 0.0001 and p = 0.0006, respectively), with a potentially supramultiplicative gene-environment interaction for the codon 751 allele. Finally, the results suggest potential supramultiplicative gene-gene interactions between CYP2E1 (c2 allele; rs3813867) and ERCC2/XPD polymorphisms that are consistent with the proposed carcinogenic pathway for vinyl chloride, which requires metabolic activation by CYP2E1 to reactive intermediates that form DNA adducts that, if not removed by DNA repair mechanisms, result in oncogenic mutations.
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Details
- Title
- Gene-environment interactions between DNA repair polymorphisms and exposure to the carcinogen vinyl chloride
- Creators
- Yongliang Li - Columbia UniversityMarie-Jeanne Marion - InsermJennifer Zipprich - Columbia UniversityRegina M. Santella - Columbia UniversityGreg Freyer - Columbia UniversityPaul W. Brandt-Rauf - Administration
- Publication Details
- Biomarkers, v 14(3), pp 148-155
- Publisher
- Taylor & Francis
- Number of pages
- 8
- Grant note
- P30-ES09089 / NIEHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) R01-OH04192 / NIOSH; United States Department of Health & Human Services; Centers for Disease Control & Prevention - USA; National Institute for Occupational Safety & Health (NIOSH) R01OH004192 / NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH; United States Department of Health & Human Services; Centers for Disease Control & Prevention - USA; National Institute for Occupational Safety & Health (NIOSH) United States EPA under the Science to Achieve Results (STAR) P30ES009089 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000265573600002
- Scopus ID
- 2-s2.0-66149107087
- Other Identifier
- 991019323671904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biotechnology & Applied Microbiology
- Toxicology