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

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 y...

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Bibliographic Details
Published in:Genome research 2019-04, Vol.29 (4), p.521-531
Main Authors: Zhivagui, Maria, Ng, Alvin W T, Ardin, Maude, Churchwell, Mona I, Pandey, Manuraj, Renard, Claire, Villar, Stephanie, Cahais, Vincent, Robitaille, Alexis, Bouaoun, Liacine, Heguy, Adriana, Guyton, Kathryn Z, Stampfer, Martha R, McKay, James, Hollstein, Monica, Olivier, Magali, Rozen, Steven G, Beland, Frederick A, Korenjak, Michael, Zavadil, Jiri
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Acrylamide
Acrylamides - toxicity
Animals
Bile ducts
Biochemistry & Molecular Biology
Biotechnology & Applied Microbiology
Cancer
Carcinogenesis
Carcinogenesis - chemically induced
Carcinogenesis - genetics
Carcinogens
Cells, Cultured
Cervix
Environmental Exposure
Epidemiology
Epoxy Compounds - toxicity
Genetics & Heredity
Genome, Human
Genomes
Humans
Kidneys
Metabolites
Mice
Mutagenesis
Mutagens - toxicity
Mutation
Neoplasms - chemically induced
Neoplasms - genetics
Tobacco
Tumor Suppressor Protein p53 - genetics
Tumors
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Summary: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.
ISSN:1088-9051
1549-5469
DOI:10.1101/gr.242453.118