Grant awarded: November 2020
A multi-disciplinary effort identifying the mutagenic effects of acrylamide in human kidney tissue could considerably advance our understanding of the role of dietary acrylamide in human cancer development.
– Assoc Prof Kim Smits
Background
People are widely exposed to acrylamide when eating carbohydrate-containing foods heated to high temperatures, such as chips or coffee, but also through cigarettes. In the body, acrylamide is turned into reactive glycidamide, known to cause cancer in rodents.
Epidemiological research into acrylamide and cancer in humans has so far provided inconsistent results. Nevertheless, the European Food Safety Authority noted that increased cancer risks could be present at current dietary acrylamide intakes. Recently, experiments in cells and mice revealed a specific mutation in DNA attributed to glycidamide effects.
In addition, glycidamide binds to DNA to form lesions that can induce mutations and thus contribute to cancer development. The glycidamide mutations were also found in human cancer genetic data but this has not yet been experimentally confirmed in humans who are known to eat acrylamide. Given the widespread acrylamide exposure and uncertainty about the consequences of this exposure, it is imperative to further study DNA mutations and damage caused by acrylamide in human tissues.
Aims and objectives
This small preliminary study evaluated the feasibility of identifying the specific DNA mutations caused by glycidamide in renal cell carcinomas and the DNA damage in kidney tissues of healthy people. In addition, it addressed whether the amount of mutations is higher in patients who eat a lot of acrylamide in their diet compared with those with a low intake.
Methods
To examine whether acrylamide- or glycidamide-induced mutations can be detected in human kidney cancer tissue, we analysed 40 archived renal cell carcinoma samples from 20 participants (10 with high and 10 with low dietary acrylamide intake) in the Netherlands Cohort Study on Diet and Cancer.
Results
DNA quality was sufficient for genome-wide mutation analysis, and sequencing produced high-quality data. Single-base substitution and mutational signature analyses indicated that the acrylamide/glycidamide signature correlated more strongly with patient age than with acrylamide intake, though the latter relationship requires further investigation in larger datasets.
Conclusions
The acrylamide/glycidamide mutational signature was detected in renal cell carcinoma cases with documented dietary acrylamide intake and reflected patients’ age at diagnosis, representing the first such observation in human cancers beyond prior in silico analyses.
Impact
Although based on a small pilot set, these findings suggest a molecular link between dietary acrylamide exposure-driven genomic imprints and age of patients with clear-cell renal cell carcinoma, supporting further studies and potential cancer-prevention measures to reduce dietary acrylamide exposure.