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Genetic Variation in Base Excision Repair Pathway Genes, Pesticide Exposure, and Prostate Cancer Risk

Background: Previous research indicates increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, evidence suggests a role of oxidative DNA damage. Objectives: Because base excision repair (BER) is the predominant pathwa...

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Autores principales: Barry, Kathryn Hughes, Koutros, Stella, Berndt, Sonja I., Andreotti, Gabriella, Hoppin, Jane A., Sandler, Dale P., Burdette, Laurie A., Yeager, Meredith, Freeman, Laura E. Beane, Lubin, Jay H., Ma, Xiaomei, Zheng, Tongzhang, Alavanja, Michael C.R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Institute of Environmental Health Sciences 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261977/
https://www.ncbi.nlm.nih.gov/pubmed/21810555
http://dx.doi.org/10.1289/ehp.1103454
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author Barry, Kathryn Hughes
Koutros, Stella
Berndt, Sonja I.
Andreotti, Gabriella
Hoppin, Jane A.
Sandler, Dale P.
Burdette, Laurie A.
Yeager, Meredith
Freeman, Laura E. Beane
Lubin, Jay H.
Ma, Xiaomei
Zheng, Tongzhang
Alavanja, Michael C.R.
author_facet Barry, Kathryn Hughes
Koutros, Stella
Berndt, Sonja I.
Andreotti, Gabriella
Hoppin, Jane A.
Sandler, Dale P.
Burdette, Laurie A.
Yeager, Meredith
Freeman, Laura E. Beane
Lubin, Jay H.
Ma, Xiaomei
Zheng, Tongzhang
Alavanja, Michael C.R.
author_sort Barry, Kathryn Hughes
collection PubMed
description Background: Previous research indicates increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, evidence suggests a role of oxidative DNA damage. Objectives: Because base excision repair (BER) is the predominant pathway involved in repairing oxidative damage, we evaluated interactions between 39 pesticides and 394 tag single-nucleotide polymorphisms (SNPs) for 31 BER genes among 776 prostate cancer cases and 1,444 male controls in a nested case–control study of white Agricultural Health Study (AHS) pesticide applicators. Methods: We used likelihood ratio tests from logistic regression models to determine p-values for interactions between three-level pesticide exposure variables (none/low/high) and SNPs (assuming a dominant model), and the false discovery rate (FDR) multiple comparison adjustment approach. Results: The interaction between fonofos and rs1983132 in NEIL3 [nei endonuclease VIII-like 3 (Escherichia coli)], which encodes a glycosylase that can initiate BER, was the most significant overall [interaction p-value (p(interact)) = 9.3 × 10(–6); FDR-adjusted p-value = 0.01]. Fonofos exposure was associated with a monotonic increase in prostate cancer risk among men with CT/TT genotypes for rs1983132 [odds ratios (95% confidence intervals) for low and high use compared with no use were 1.65 (0.91, 3.01) and 3.25 (1.78, 5.92), respectively], whereas fonofos was not associated with prostate cancer risk among men with the CC genotype. Carbofuran and S-ethyl dipropylthiocarbamate (EPTC) interacted similarly with rs1983132; however, these interactions did not meet an FDR < 0.2. Conclusions: Our significant finding regarding fonofos is consistent with previous AHS findings of increased prostate cancer risk with fonofos exposure among those with a family history of prostate cancer. Although requiring replication, our findings suggest a role of BER genetic variation in pesticide-associated prostate cancer risk.
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spelling pubmed-32619772012-01-20 Genetic Variation in Base Excision Repair Pathway Genes, Pesticide Exposure, and Prostate Cancer Risk Barry, Kathryn Hughes Koutros, Stella Berndt, Sonja I. Andreotti, Gabriella Hoppin, Jane A. Sandler, Dale P. Burdette, Laurie A. Yeager, Meredith Freeman, Laura E. Beane Lubin, Jay H. Ma, Xiaomei Zheng, Tongzhang Alavanja, Michael C.R. Environ Health Perspect Research Background: Previous research indicates increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, evidence suggests a role of oxidative DNA damage. Objectives: Because base excision repair (BER) is the predominant pathway involved in repairing oxidative damage, we evaluated interactions between 39 pesticides and 394 tag single-nucleotide polymorphisms (SNPs) for 31 BER genes among 776 prostate cancer cases and 1,444 male controls in a nested case–control study of white Agricultural Health Study (AHS) pesticide applicators. Methods: We used likelihood ratio tests from logistic regression models to determine p-values for interactions between three-level pesticide exposure variables (none/low/high) and SNPs (assuming a dominant model), and the false discovery rate (FDR) multiple comparison adjustment approach. Results: The interaction between fonofos and rs1983132 in NEIL3 [nei endonuclease VIII-like 3 (Escherichia coli)], which encodes a glycosylase that can initiate BER, was the most significant overall [interaction p-value (p(interact)) = 9.3 × 10(–6); FDR-adjusted p-value = 0.01]. Fonofos exposure was associated with a monotonic increase in prostate cancer risk among men with CT/TT genotypes for rs1983132 [odds ratios (95% confidence intervals) for low and high use compared with no use were 1.65 (0.91, 3.01) and 3.25 (1.78, 5.92), respectively], whereas fonofos was not associated with prostate cancer risk among men with the CC genotype. Carbofuran and S-ethyl dipropylthiocarbamate (EPTC) interacted similarly with rs1983132; however, these interactions did not meet an FDR < 0.2. Conclusions: Our significant finding regarding fonofos is consistent with previous AHS findings of increased prostate cancer risk with fonofos exposure among those with a family history of prostate cancer. Although requiring replication, our findings suggest a role of BER genetic variation in pesticide-associated prostate cancer risk. National Institute of Environmental Health Sciences 2011-08-02 2011-12 /pmc/articles/PMC3261977/ /pubmed/21810555 http://dx.doi.org/10.1289/ehp.1103454 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
Barry, Kathryn Hughes
Koutros, Stella
Berndt, Sonja I.
Andreotti, Gabriella
Hoppin, Jane A.
Sandler, Dale P.
Burdette, Laurie A.
Yeager, Meredith
Freeman, Laura E. Beane
Lubin, Jay H.
Ma, Xiaomei
Zheng, Tongzhang
Alavanja, Michael C.R.
Genetic Variation in Base Excision Repair Pathway Genes, Pesticide Exposure, and Prostate Cancer Risk
title Genetic Variation in Base Excision Repair Pathway Genes, Pesticide Exposure, and Prostate Cancer Risk
title_full Genetic Variation in Base Excision Repair Pathway Genes, Pesticide Exposure, and Prostate Cancer Risk
title_fullStr Genetic Variation in Base Excision Repair Pathway Genes, Pesticide Exposure, and Prostate Cancer Risk
title_full_unstemmed Genetic Variation in Base Excision Repair Pathway Genes, Pesticide Exposure, and Prostate Cancer Risk
title_short Genetic Variation in Base Excision Repair Pathway Genes, Pesticide Exposure, and Prostate Cancer Risk
title_sort genetic variation in base excision repair pathway genes, pesticide exposure, and prostate cancer risk
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261977/
https://www.ncbi.nlm.nih.gov/pubmed/21810555
http://dx.doi.org/10.1289/ehp.1103454
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