title: Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer.
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.
authors.affiliation: Department of Environmental & Occupational Health, Florida International University, Miami, FL 33199, USA. droy@fiu.edu.
authors.forename: Deodutta
authors.initials: D
authors.lastname: Roy
authors.affiliation: Department of Environmental & Occupational Health, Florida International University, Miami, FL 33199, USA. mmorg003@fiu.edu.
authors.forename: Marisa
authors.initials: M
authors.lastname: Morgan
authors.affiliation: Department of Biostatistics, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL 33199, USA. cyoo@fiu.edu.
authors.forename: Changwon
authors.initials: C
authors.lastname: Yoo
authors.affiliation: Department of Environmental & Occupational Health, Florida International University, Miami, FL 33199, USA. adeoraj@fiu.edu.
authors.forename: Alok
authors.initials: A
authors.lastname: Deoraj
authors.affiliation: BMSNF Inc., Aventura, FL 33180, USA. roy.sandhya09@gmail.com.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Roy
authors.affiliation: Department of Physics, GKPD College, Karpoorigram, Samastipur 848129, India. sundrian9@gmail.com.
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Yadav
authors.affiliation: Department of Environmental & Occupational Health, Florida International University, Miami, FL 33199, USA. mgaro005@fiu.edu.
authors.forename: Mohannad
authors.initials: M
authors.lastname: Garoub
authors.affiliation: Department of Environmental & Occupational Health, Florida International University, Miami, FL 33199, USA. hassagga@fiu.edu.
authors.forename: Hamza
authors.initials: H
authors.lastname: Assaggaf
authors.affiliation: Department of Environmental & Occupational Health, Florida International University, Miami, FL 33199, USA. mdoke001@fiu.edu.
authors.forename: Mayur
authors.initials: M
authors.lastname: Doke
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D052244:Endocrine Disruptors / Q000633:toxicity*; D004715:Endometriosis / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D004967:Estrogens / Q000235:genetics; D005260:Female; D015894:Genome, Human; D006801:Humans
chemical_list: D000393:Air Pollutants; D052244:Endocrine Disruptors; D004967:Estrogens
keywords: PCBs; bioinformatics; bisphenol A; breast cancer; endocrine disruptors; endometriosis; genomics; phthalates