Experimental and pan-cancer genome analyses reveal widespread contribution of acrylamide exposure to carcinogenesis in humans

Genome Res. 2019 Apr;29(4):521-531. doi: 10.1101/gr.242453.118. Epub 2019 Mar 7.


Humans are frequently exposed to acrylamide, a probable human carcinogen found in commonplace sources such as most heated starchy foods or tobacco smoke. Prior evidence has shown that acrylamide causes cancer in rodents, yet epidemiological studies conducted to date are limited and, thus far, have yielded inconclusive data on association of human cancers with acrylamide exposure. In this study, we experimentally identify a novel and unique mutational signature imprinted by acrylamide through the effects of its reactive metabolite glycidamide. We next show that the glycidamide mutational signature is found in a full one-third of approximately 1600 tumor genomes corresponding to 19 human tumor types from 14 organs. The highest enrichment of the glycidamide signature was observed in the cancers of the lung (88% of the interrogated tumors), liver (73%), kidney (>70%), bile duct (57%), cervix (50%), and, to a lesser extent, additional cancer types. Overall, our study reveals an unexpectedly extensive contribution of acrylamide-associated mutagenesis to human cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acrylamides / toxicity*
  • Animals
  • Carcinogenesis / chemically induced
  • Carcinogenesis / genetics*
  • Cells, Cultured
  • Environmental Exposure*
  • Epoxy Compounds / toxicity
  • Genome, Human
  • Humans
  • Mice
  • Mutagens / toxicity*
  • Mutation*
  • Neoplasms / chemically induced
  • Neoplasms / genetics*
  • Tumor Suppressor Protein p53 / genetics


  • Acrylamides
  • Epoxy Compounds
  • Mutagens
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • glycidamide