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

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Date
2019-03-07
Authors
Zhivagui, Maria
Ng, Alvin WT
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
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Abstract
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.
Type
Journal article
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https://hdl.handle.net/10161/18203
Published Version (Please cite this version)
10.1101/gr.242453.118
Publication Info
Zhivagui, Maria; Ng, Alvin WT; Ardin, Maude; Churchwell, Mona I; Pandey, Manuraj; Renard, Claire; ... Zavadil, Jiri (2019). Experimental and pan-cancer genome analyses reveal widespread contribution of acrylamide exposure to carcinogenesis in humans. Genome research. 10.1101/gr.242453.118. Retrieved from https://hdl.handle.net/10161/18203.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Rozen

Steven George Rozen

Associate Professor in Psychiatry and Behavioral Sciences
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