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Int. J. Mol. Sci. 2015, 16(10), 25285-25322; doi:10.3390/ijms161025285

Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

1
Department of Environmental & Occupational Health, Florida International University, Miami, FL 33199, USA
2
Department of Biostatistics, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA
3
BMSNF Inc., Aventura, FL 33180, USA
4
Department of Physics, GKPD College, Karpoorigram, Samastipur 848129, India
*
Author to whom correspondence should be addressed.
Academic Editor: Paul B. Tchounwou
Received: 18 August 2015 / Revised: 10 October 2015 / Accepted: 12 October 2015 / Published: 23 October 2015
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Abstract

We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC) and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs), bisphenols (BPs), and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA) and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by exposure to PCBs, phthalate or BPA. EDCs-modified genes in breast neoplasms and endometriosis are part of steroid hormone signaling and inflammation pathways. All three EDCs–PCB 153, phthalates, and BPA influenced five common genes—CYP19A1, EGFR, ESR2, FOS, and IGF1—in breast cancer as well as in endometriosis. These genes are environmentally and estrogen responsive, altered in human breast and uterine tumors and endometriosis lesions, and part of Mitogen Activated Protein Kinase (MAPK) signaling pathways in cancer. Our findings suggest that breast cancer and endometriosis share some common environmental and molecular risk factors. View Full-Text
Keywords: bioinformatics; breast cancer; bisphenol A; endocrine disruptors; endometriosis; genomics; PCBs; phthalates bioinformatics; breast cancer; bisphenol A; endocrine disruptors; endometriosis; genomics; PCBs; phthalates
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Roy, D.; Morgan, M.; Yoo, C.; Deoraj, A.; Roy, S.; Yadav, V.K.; Garoub, M.; Assaggaf, H.; Doke, M. Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer. Int. J. Mol. Sci. 2015, 16, 25285-25322.

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