Impact of multi-mycotoxin exposure on kidney cancer risk: uniting a large-scale epidemiological design & next-generation sequencing coupled with public cancer genomic data mining

01 January 2018 → 31 December 2021
Research Foundation - Flanders (FWO)
Research disciplines
No data available
mycotoxin kidney cancer
Project description

Mycotoxins are fungal toxins that frequently contaminate food & feed, and can contribute to a diversity of adverse health effects in humans such as carcinogenicity and nephrotoxicity. The kidney is a major target of mycotoxins. In addition, multiple mycotoxins can co-occur on one crop due to multi-fungal contamination. Interactions between co-occurring mycotoxins can be additive or synergistic. To date, there is no convincing epidemiological data on the effect of multi-mycotoxin exposures on human kidney cancer (KC), and evidence from mechanistic studies is limited. This project proposal combines a high-quality large-scale epidemiological design with an innovative mechanistic arm using established in vitro & in vivo exposure systems, and next-generation sequencing coupled with public cancer genomic data mining. Objectives are to (1) investigate associations between estimated dietary mycotoxin exposures and KC risk, using data from the full European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n=521,448) and mycotoxin occurrence data from EFSA; (2) measure mycotoxin biomarkers in plasma samples using UHPLC-MS/MS of a KC case-control study nested in EPIC (n=556 pairs) to investigate pathways of mycotoxin exposures and their association with KC risk; and (3) experimentally determine genomewide mutation spectra, extracted from public human cancer genomics data, associated with exposure to putatively carcinogenic mycotoxins OTA, FB1 & DON.