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

Almudena Espin-Perez*, Dennie G. A. J. Hebels, Hannu Kiviranta, Panu Rantakokko, Panagiotis Georgiadis, Maria Botsivali, Ingvar A. Bergdahl, Domenico Palli, Florentin Spath, Anders Johansson, Marc Chadeau-Hyam, Soterios A. Kyrtopoulos, Jos C. S. Kleinjans, Theo M. C. M. de Kok

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Web of Science)

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.

Original languageEnglish
Article number746
Pages (from-to)1-12
Number of pages12
JournalScientific Reports
Volume9
DOIs
Publication statusPublished - 24 Jan 2019

Keywords

  • PERSISTENT ORGANIC POLLUTANTS
  • GENE-EXPRESSION ANALYSIS
  • CARDIOVASCULAR-DISEASE
  • CARCINOMA-CELLS
  • IMMUNE-SYSTEM
  • CANCER
  • LYMPHOMA
  • EXPOSURE
  • SUPPRESSION
  • HEALTH

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