Systemic sclerosis and occupational silica or solvent exposure: investigating epidemiology, gene-environment interactions and objective markers of exposure to improve occupational epidemiology, risk assessment and prevention.
Systemic sclerosis is a rare autoimmune disease that can develop in genetically predisposed individuals upon exposure to – at present largely unknown- environmental triggers. The best available evidence supports a link between systemic sclerosis and job exposure to silica or solvents. Due to the rarity of the disease many questions remain open: what is the critical threshold of exposure above which disease will develop? Is intensity of exposure the most important factor or rather the duration, or both? By what mechanism do silica or solvents cause systemic sclerosis? What is the specific genetic background that renders an individual susceptible? Europe has acknowledged that it is a top research priority to elucidate the role of the environment in disease development. This is highly relevant as it would allow for true preventive strategies lowering disease incidence and lead to better understanding of disease processes and identification of new therapeutic targets. In this project, we will perform a large epidemiological study to clarify the association between occupational exposure and systemic sclerosis. We will determine genetic backgrounds to evaluate the relation between exposure, genetics and disease characteristics. We will evaluate objective markers of exposure. This will lead to substantial progress in the field and shed light on the link between environmental exposure and human disease.