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Sci Rep. 2019 Jan 24;9(1):746. doi: 10.1038/s41598-018-37449-y.

Identification of Sex-Specific Transcriptome Responses to Polychlorinated Biphenyls (PCBs).

Author information

1
Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands. a.espin@maastrichtuniversity.nl.
2
Department of Toxicogenomics, Maastricht University, Maastricht, The Netherlands.
3
MERLN Institute for Technology-inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands.
4
Department of Health Protection, Chemicals and Health Unit, National Institute for Health and Welfare, Kuopio, Finland.
5
Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
6
Department of Biobank Research, and Occupational and Environmental Medicine, Umeå University, Umeå, Sweden.
7
Molecular and Nutritional Epidemiology UnitI, ISPO Cancer Prevention and Research Institute, Florence, Italy.
8
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

Abstract

PCBs are classified as xenoestrogens and carcinogens and their health risks may be sex-specific. To identify potential sex-specific responses to PCB-exposure we established gene expression profiles in a population study subdivided into females and males. Gene expression profiles were determined in a study population consisting of 512 subjects from the EnviroGenomarkers project, 217 subjects who developed lymphoma and 295 controls were selected in later life. We ran linear mixed models in order to find associations between gene expression and exposure to PCBs, while correcting for confounders, in particular distribution of white blood cells (WBC), as well as random effects. The analysis was subdivided according to sex and development of lymphoma in later life. The changes in gene expression as a result of exposure to the six studied PCB congeners were sex- and WBC type specific. The relatively large number of genes that are significantly associated with PCB-exposure in the female subpopulation already indicates different biological response mechanisms to PCBs between the two sexes. The interaction analysis between different PCBs and WBCs provides only a small overlap between sexes. In males, cancer-related pathways and in females immune system-related pathways are identified in association with PCBs and WBCs. Future lymphoma cases and controls for both sexes show different responses to the interaction of PCBs with WBCs, suggesting a role of the immune system in PCB-related cancer development.

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