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Polymorphisms in Nucleotide Excision Repair Genes, Arsenic Exposure, and Non-Melanoma Skin Cancer in New Hampshire

BACKGROUND: Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC). OBJECTIVE: We tested whether polymorphisms in the NER genes XPA (A23G...

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Autores principales: Applebaum, Katie M., Karagas, Margaret R., Hunter, David J., Catalano, Paul J., Byler, Steven H., Morris, Steve, Nelson, Heather H.
Formato: Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1940098/
https://www.ncbi.nlm.nih.gov/pubmed/17687452
http://dx.doi.org/10.1289/ehp.10096
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author Applebaum, Katie M.
Karagas, Margaret R.
Hunter, David J.
Catalano, Paul J.
Byler, Steven H.
Morris, Steve
Nelson, Heather H.
author_facet Applebaum, Katie M.
Karagas, Margaret R.
Hunter, David J.
Catalano, Paul J.
Byler, Steven H.
Morris, Steve
Nelson, Heather H.
author_sort Applebaum, Katie M.
collection PubMed
description BACKGROUND: Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC). OBJECTIVE: We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp312Asn and Lys751Gln) modify the association between arsenic and NMSC. METHODS: Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail clippings. The analysis included 880 cases of BCC, 666 cases of SCC, and 780 controls. RESULTS: There was an increased BCC risk associated with high arsenic exposure among those homozygous variant for XPA [odds ratio (OR) = 1.8; 95% confidence interval (CI), 0.9–3.7]. For XPD, having variation at both loci (312Asn and 751Gln) occurred less frequently among BCC and SCC cases compared with controls (OR = 0.8; 95% CI, 0.6–1.0) for both case groups. In the stratum of subjects who have variant for both XPD polymorphisms, there was a 2-fold increased risk of SCC associated with elevated arsenic (OR = 2.2; 95% CI, 1.0–5.0). The test for interaction between XPD and arsenic in SCC was of borderline significance (p < 0.07, 3 degrees of freedom). CONCLUSIONS: Our findings indicate a reduced NMSC risk in relation to XPD Asp312Asn and Lys751Gln variants. Further, these data support the hypothesis that NER polymorphisms may modify the association between NMSC and arsenic.
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spelling pubmed-19400982007-08-08 Polymorphisms in Nucleotide Excision Repair Genes, Arsenic Exposure, and Non-Melanoma Skin Cancer in New Hampshire Applebaum, Katie M. Karagas, Margaret R. Hunter, David J. Catalano, Paul J. Byler, Steven H. Morris, Steve Nelson, Heather H. Environ Health Perspect Research BACKGROUND: Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC). OBJECTIVE: We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp312Asn and Lys751Gln) modify the association between arsenic and NMSC. METHODS: Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail clippings. The analysis included 880 cases of BCC, 666 cases of SCC, and 780 controls. RESULTS: There was an increased BCC risk associated with high arsenic exposure among those homozygous variant for XPA [odds ratio (OR) = 1.8; 95% confidence interval (CI), 0.9–3.7]. For XPD, having variation at both loci (312Asn and 751Gln) occurred less frequently among BCC and SCC cases compared with controls (OR = 0.8; 95% CI, 0.6–1.0) for both case groups. In the stratum of subjects who have variant for both XPD polymorphisms, there was a 2-fold increased risk of SCC associated with elevated arsenic (OR = 2.2; 95% CI, 1.0–5.0). The test for interaction between XPD and arsenic in SCC was of borderline significance (p < 0.07, 3 degrees of freedom). CONCLUSIONS: Our findings indicate a reduced NMSC risk in relation to XPD Asp312Asn and Lys751Gln variants. Further, these data support the hypothesis that NER polymorphisms may modify the association between NMSC and arsenic. National Institute of Environmental Health Sciences 2007-08 2007-06-11 /pmc/articles/PMC1940098/ /pubmed/17687452 http://dx.doi.org/10.1289/ehp.10096 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.
spellingShingle Research
Applebaum, Katie M.
Karagas, Margaret R.
Hunter, David J.
Catalano, Paul J.
Byler, Steven H.
Morris, Steve
Nelson, Heather H.
Polymorphisms in Nucleotide Excision Repair Genes, Arsenic Exposure, and Non-Melanoma Skin Cancer in New Hampshire
title Polymorphisms in Nucleotide Excision Repair Genes, Arsenic Exposure, and Non-Melanoma Skin Cancer in New Hampshire
title_full Polymorphisms in Nucleotide Excision Repair Genes, Arsenic Exposure, and Non-Melanoma Skin Cancer in New Hampshire
title_fullStr Polymorphisms in Nucleotide Excision Repair Genes, Arsenic Exposure, and Non-Melanoma Skin Cancer in New Hampshire
title_full_unstemmed Polymorphisms in Nucleotide Excision Repair Genes, Arsenic Exposure, and Non-Melanoma Skin Cancer in New Hampshire
title_short Polymorphisms in Nucleotide Excision Repair Genes, Arsenic Exposure, and Non-Melanoma Skin Cancer in New Hampshire
title_sort polymorphisms in nucleotide excision repair genes, arsenic exposure, and non-melanoma skin cancer in new hampshire
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1940098/
https://www.ncbi.nlm.nih.gov/pubmed/17687452
http://dx.doi.org/10.1289/ehp.10096
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