March 7, 2019

expert reaction to mutagenic effects of acrylamide in humans

Research published in Genome Research demonstrates that acrylamide can introduce tumor-specific mutations in humans.

Prof Kevin McConway, Emeritus Professor of Applied Statistics, The Open University, said:

“There’s reasonable evidence that acrylamide has the potential to affect the risk of cancer in humans, but whether it actually does, when humans are exposed at the typical levels they might encounter in everyday life, is another question. The evidence on that is limited and generally inconclusive. This thorough new research does add to what is known about acrylamide and human cancers, but it’s important to understand that it does so in a particular way and that their new results still can’t establish a clear link between acrylamide and human cancer risk.

“One thing that’s been missing so far is an understanding of possible mechanisms inside the body whereby acrylamide might actually cause an increase in cancer risk. The new research throws light on that. The researchers used experiments on mouse cells to establish that glycidamide can produce distinctive patterns of mutation. (Glycidamide is produced in the body from acrylamide.) They then looked to see whether these patterns of mutation could be observed in a wide range of samples of genomes from known human cancers, and they did detect the patterns in several different types of cancer, though they were not always present. This shows that glycidamide can cause changes in DNA that can be observed in some cancers. It cannot establish that the changes actually cause the cancers in question – that’s not how these things work. So this new research does establish a route by which acrylamide could lead to cancers, via glycidamide and the DNA changes it can produce. That’s very useful information, but it’s not yet a smoking gun showing that acrylamide definitely does cause the cancers.

“Because of that, the top line of the press release, ‘Experimental and pan-cancer genome analyses reveal widespread contribution of acrylamide exposure to carcinogenesis in humans’, is very misleading and exaggerated if read in what’s perhaps the obvious way. The research does not point to a widespread set of human cancer cases which were caused, or contributed to, by acrylamide exposure. All it points to is a potential mechanism by which acrylamide could cause cancers, and that potential mechanism applies to more than just one or two cancer types, so the only ‘widespread’ thing is that the mechanism could work in several cancer types.”

Associate Professor Oliver Jones, Associate Professor of Analytical Chemistry, RMIT University, said:

“This study is an interesting and carefully carried out piece of work in which the authors found what might be termed a sort of mutational fingerprint in DNA exposed to glycidamide, a substance which is commonly formed from another compound – acrylamide. Acrylamide is found in many industrial processes and can also form when some starchy foods are cooked. The authors found these signatures using cell cultures and then found the same fingerprint in existing, publicly available cancer genome data.

“However, while the work is clever and enhances our understanding of how some cancers may possibly occur, for most people this will make no difference to their everyday lives. Just because something can happen does not mean that it does happen. While this study should get credit for giving us a better understanding of how some cancers may occur, the potential risks of acrylamide in food are generally overstated.

“Despite a lot of work in the area there is still no firm link between the levels of acrylamide in our everyday diet and cancer, and this new study does not change that.”

Prof Andrew Sharrocks, Professor of Molecular Biology, University of Manchester, said:

“This is an interesting study that provides definitive links between acrylamide and mutations in human cells. This is important as acrylamide is a known carcinogen which is present in some foods cooked at high temperatures and tobacco but until now the links have been mainly correlative.

“These correlative studies provide links between exposure to acrylamide and the chances of getting cancer. This paper demonstrates that the association goes beyond correlative and they identify unique molecular signatures in human cancers which make the links more definitive. This might obviously provide linkages with dietary and lifestyle influences, but that link is not provided in this paper and definitive proof would be needed to show that excessive exposure to acrylamide leads to an increased frequency of mutational signatures in an individual. Nevertheless, this paper strongly suggests this should be the case.”

Prof Justin Stebbing, NIHR Research Professor of Cancer Medicine and Medical Oncology, Imperial College London, said:

“The role of acrylamide and its by-products in causing cancer has been of interest especially as it’s found in tobacco but also certain foods. This research shows how it can damage the genome and cause mutations. In fact, the scientists use lots of models combining sequencing of DNA with computational analyses and describe an acrylamide signature. It helps us understand it better at a molecular level, but we are not yet at the stage where we’re saying it directly causes cancer in humans.

“Humans are frequently exposed to acrylamide, which may be a human carcinogen found in many commonplace sources such as most heated starchy foods or tobacco smoke. Prior evidence has shown that acrylamide causes cancer in animal models, yet many studies conducted to date are limited and thus far yielded inconclusive data on association of human cancers with acrylamide exposure.  This research – an integrated analysis – shows that acrylamide damages the genome and causes mutations.”

‘Experimental and pan-cancer genome analyses reveal widespread contribution of acrylamide exposure to carcinogenesis in humans’ by Zhivagui et al. was published in Genome Research at 18:00 UK time on Thursday 7 March.

Declared interests

Prof Kevin McConway: “Kevin McConway is a Trustee of the Science Media Centre”

Associate Professor Oliver Jones: “No conflict of interest to declare.”

Prof Andrew Sharrocks: “I have no conflicts with this.”

Prof Justin Stebbing: “None.”