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Low dose environmental radon exposure and breast tumor gene expression.

Abstract：

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.

journal_name

BMC Cancer

journal_title

BMC cancer

authors

Peng C,DuPre N,VoPham T,Heng YJ,Baker GM,Rubadue CA,Glass K,Sonawane A,Zeleznik O,Kraft P,Hankinson SE,Eliassen AH,Hart JE,Laden F,Tamimi RM

doi

10.1186/s12885-020-07184-7

subject

Has Abstract

pub_date

2020-07-28 00:00:00

pages

695

issue

issn

1471-2407

pii

10.1186/s12885-020-07184-7

journal_volume

pub_type

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Low dose environmental radon exposure and breast tumor gene expression.