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.