Integrated bioinformatics, environmental epidemiologic and genomic approaches to identify environmental and molecular links between endometriosis and breast cancer

Deodutta Roy, Marisa Morgan, Changwon Yoo, Alok Deoraj, Sandhya Roy, Vijay Kumar Yadav, Mohannad Garoub, Hamza Assaggaf, Mayur Doke

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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.

Original languageEnglish
Pages (from-to)25285-25322
Number of pages38
JournalInternational Journal of Molecular Sciences
Volume16
Issue number10
DOIs
StatePublished - 23 Oct 2015
Externally publishedYes

Keywords

  • Bioinformatics
  • Bisphenol A
  • Breast cancer
  • Endocrine disruptors
  • Endometriosis
  • Genomics
  • PCBs
  • Phthalates

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