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PCB exposure and potential future cancer incidence in Slovak children: an assessment from molecular finger printing by Ingenuity Pathway Analysis (IPA®) derived from experimental and epidemiological investigations |
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| Authors: | Ghosh Somiranjan Loffredo Christopher A Mitra Partha S Trnovec Tomas Palkovicova Murinova Lubica Sovcikova Eva Hoffman Eric P Makambi Kepher H Dutta Sisir K |
| Institution: | 1.Molecular Genetics Laboratory, Department of Biology, Howard University, 415 College Street, NW, Room 408, EE Just Hall, Washington, DC, 20059, USA ;2.Department of Pediatrics and Child Health, College of Medicine, Howard University, Washington, DC, 20059, USA ;3.Departments of Oncology and of Biostatistics, Georgetown University, Washington, DC, 20057, USA ;4.Department of Environmental Medicine, Faculty of Public Health, Slovak Medical University, Bratislava, Slovak Republic ;5.School of Pharmacy and Pharmaceutical Science, Binghamton University, State University of New York, Binghamton, NY, 13902, USA ;6.Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University, Washington, DC, 20057, USA ; |
| Abstract: | The risk of cancer due to PCB exposure in humans is highly debated. In eastern Slovakia, high exposure of the population to organochlorines (especially PCBs) was associated with various disease and disorder pathways, viz., endocrine disruption, metabolic disorder & diabetes, and cancer, thereby disturbing several cellular processes, including protein synthesis, stress response, and apoptosis. We have evaluated a Slovak cohort (45-month children, at lower and higher levels of PCB exposure from the environment) for disease and disorder development to develop early disease cancer biomarkers that could shed new light on possible mechanisms for the genesis of cancers under such chemical exposures, and identify potential avenues for prevention. Microarray studies of global gene expression were conducted from the 45-month-old children on the Affymetrix platform followed by Ingenuity Pathway Analysis (IPA®) to associate the affected genes with their mechanistic pathways. High-throughput qRT-PCR TaqMan low-density array (TLDA) was performed to further validate the selected genes on the whole blood cells of the most highly exposed children from the study cohort (n = 71). TP53, MYC, BCL2, and LRP12 differential gene expressions suggested strong relationships between potential future tumor promotion and PCB exposure in Slovak children. The IPA analysis further detected the most important signaling pathways, including molecular mechanism of cancers, prostate cancer signaling, ovarian cancer signaling, P53 signaling, oncostatin M signaling, and their respective functions (viz., prostate cancer, breast cancer, progression of tumor, growth of tumor, and non-Hodgkin’s disease). The results suggest that PCB exposures, even at the early age of these children, may have lifelong consequences for the future development of chronic diseases. |
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