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Low dose environmental radon exposure and breast tumor gene expression

BACKGROUND: The International Agency for Research on Cancer classified radon and its decay-products as Group-1-human-carcinogens, and with the current knowledge they are linked specifically to lung cancer. Biokinetic models predict that radon could deliver a carcinogenic dose to breast tissue. Our p...

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Autores principales: Peng, Cheng, DuPre, Natalie, VoPham, Trang, Heng, Yujing J., Baker, Gabrielle M., Rubadue, Christopher A., Glass, Kimberly, Sonawane, Abhijeet, Zeleznik, Oana, Kraft, Peter, Hankinson, Susan E., Eliassen, A. Heather, Hart, Jaime E., Laden, Francine, Tamimi, Rulla M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385902/
https://www.ncbi.nlm.nih.gov/pubmed/32723380
http://dx.doi.org/10.1186/s12885-020-07184-7
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author Peng, Cheng
DuPre, Natalie
VoPham, Trang
Heng, Yujing J.
Baker, Gabrielle M.
Rubadue, Christopher A.
Glass, Kimberly
Sonawane, Abhijeet
Zeleznik, Oana
Kraft, Peter
Hankinson, Susan E.
Eliassen, A. Heather
Hart, Jaime E.
Laden, Francine
Tamimi, Rulla M.
author_facet Peng, Cheng
DuPre, Natalie
VoPham, Trang
Heng, Yujing J.
Baker, Gabrielle M.
Rubadue, Christopher A.
Glass, Kimberly
Sonawane, Abhijeet
Zeleznik, Oana
Kraft, Peter
Hankinson, Susan E.
Eliassen, A. Heather
Hart, Jaime E.
Laden, Francine
Tamimi, Rulla M.
author_sort Peng, Cheng
collection PubMed
description BACKGROUND: The International Agency for Research on Cancer classified radon and its decay-products as Group-1-human-carcinogens, and with the current knowledge they are linked specifically to lung cancer. Biokinetic models predict that radon could deliver a carcinogenic dose to breast tissue. Our previous work suggested that low-dose radon was associated with estrogen-receptor (ER)-negative breast cancer risk. However, there is limited research to examine the role of radon in breast cancer biology at the tissue level. We aim to understand molecular pathways linking radon exposure with breast cancer biology using transcriptome-wide-gene-expression from breast tumor and normal-adjacent tissues. METHODS: Our study included 943 women diagnosed with breast cancer from the Nurses’ Health Study (NHS) and NHSII. We estimated cumulative radon concentration for each participant up-to the year of breast cancer diagnosis by linking residential addresses with a radon exposure model. Transcriptome-wide-gene-expression was measured with the Affymetrix-Glue-Human-Transcriptome-Array-3.0 and Human-Transcriptome-Array-2.0. We performed covariate-adjusted linear-regression for individual genes and further employed pathway-analysis. All analyses were conducted separately for tumor and normal-adjacent samples and by ER-status. RESULTS: No individual gene was associated with cumulative radon exposure in ER-positive tumor, ER-negative tumor, or ER-negative normal-adjacent tissues at FDR < 5%. In ER-positive normal-adjacent samples, PLCH2—reached transcriptome-wide-significance (FDR < 5%). Gene-set-enrichment-analyses identified 2-upregulated pathways (MAPK signaling and phosphocholine biosynthesis) enriched at FDR < 25% in ER-negative tumors and normal-adjacent tissues, and both pathways have been previously reported to play key roles in ionizing radiation induced tumorigenesis in experimental settings. CONCLUSION: Our findings provide insights into the molecular pathways of radon exposure that may influence breast cancer etiology.
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spelling pubmed-73859022020-07-30 Low dose environmental radon exposure and breast tumor gene expression Peng, Cheng DuPre, Natalie VoPham, Trang Heng, Yujing J. Baker, Gabrielle M. Rubadue, Christopher A. Glass, Kimberly Sonawane, Abhijeet Zeleznik, Oana Kraft, Peter Hankinson, Susan E. Eliassen, A. Heather Hart, Jaime E. Laden, Francine Tamimi, Rulla M. BMC Cancer Research Article BACKGROUND: The International Agency for Research on Cancer classified radon and its decay-products as Group-1-human-carcinogens, and with the current knowledge they are linked specifically to lung cancer. Biokinetic models predict that radon could deliver a carcinogenic dose to breast tissue. Our previous work suggested that low-dose radon was associated with estrogen-receptor (ER)-negative breast cancer risk. However, there is limited research to examine the role of radon in breast cancer biology at the tissue level. We aim to understand molecular pathways linking radon exposure with breast cancer biology using transcriptome-wide-gene-expression from breast tumor and normal-adjacent tissues. METHODS: Our study included 943 women diagnosed with breast cancer from the Nurses’ Health Study (NHS) and NHSII. We estimated cumulative radon concentration for each participant up-to the year of breast cancer diagnosis by linking residential addresses with a radon exposure model. Transcriptome-wide-gene-expression was measured with the Affymetrix-Glue-Human-Transcriptome-Array-3.0 and Human-Transcriptome-Array-2.0. We performed covariate-adjusted linear-regression for individual genes and further employed pathway-analysis. All analyses were conducted separately for tumor and normal-adjacent samples and by ER-status. RESULTS: No individual gene was associated with cumulative radon exposure in ER-positive tumor, ER-negative tumor, or ER-negative normal-adjacent tissues at FDR < 5%. In ER-positive normal-adjacent samples, PLCH2—reached transcriptome-wide-significance (FDR < 5%). Gene-set-enrichment-analyses identified 2-upregulated pathways (MAPK signaling and phosphocholine biosynthesis) enriched at FDR < 25% in ER-negative tumors and normal-adjacent tissues, and both pathways have been previously reported to play key roles in ionizing radiation induced tumorigenesis in experimental settings. CONCLUSION: Our findings provide insights into the molecular pathways of radon exposure that may influence breast cancer etiology. BioMed Central 2020-07-28 /pmc/articles/PMC7385902/ /pubmed/32723380 http://dx.doi.org/10.1186/s12885-020-07184-7 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Peng, Cheng
DuPre, Natalie
VoPham, Trang
Heng, Yujing J.
Baker, Gabrielle M.
Rubadue, Christopher A.
Glass, Kimberly
Sonawane, Abhijeet
Zeleznik, Oana
Kraft, Peter
Hankinson, Susan E.
Eliassen, A. Heather
Hart, Jaime E.
Laden, Francine
Tamimi, Rulla M.
Low dose environmental radon exposure and breast tumor gene expression
title Low dose environmental radon exposure and breast tumor gene expression
title_full Low dose environmental radon exposure and breast tumor gene expression
title_fullStr Low dose environmental radon exposure and breast tumor gene expression
title_full_unstemmed Low dose environmental radon exposure and breast tumor gene expression
title_short Low dose environmental radon exposure and breast tumor gene expression
title_sort low dose environmental radon exposure and breast tumor gene expression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385902/
https://www.ncbi.nlm.nih.gov/pubmed/32723380
http://dx.doi.org/10.1186/s12885-020-07184-7
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