Experimental and pan-cancer genome analyses reveal widespread contribution of acrylamide exposure to carcinogenesis in humans
| Autor: | James McKay, Vincent Cahais, Michael Korenjak, Claire Renard, Adriana Heguy, Monica Hollstein, Liacine Bouaoun, Alexis Robitaille, Stephanie Villar, Martha R. Stampfer, Maude Ardin, Steven G. Rozen, Maria Zhivagui, Mona I. Churchwell, Kathryn Z. Guyton, Alvin Wei Tian Ng, Magali Olivier, Jiri Zavadil, Manuraj Pandey, Frederick A. Beland |
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| Rok vydání: | 2019 |
| Předmět: |
Carcinogenesis
medicine.disease_cause Genome Medical and Health Sciences Tobacco smoke chemistry.chemical_compound Mice 0302 clinical medicine Neoplasms 2.2 Factors relating to the physical environment 2.1 Biological and endogenous factors Aetiology Lung Cells Cultured Genetics (clinical) Cancer 0303 health sciences Mutation Cultured Liver Disease Lung Cancer Environmental exposure Biological Sciences Acrylamide Human Bioinformatics Cells Biology 03 medical and health sciences Rare Diseases Tobacco medicine Genetics Animals Humans Carcinogen 030304 developmental biology Acrylamides Tobacco Smoke and Health Genome Human Research Prevention Human Genome Environmental Exposure medicine.disease chemistry Cancer research Epoxy Compounds Tumor Suppressor Protein p53 Digestive Diseases 030217 neurology & neurosurgery Mutagens |
| Zdroj: | Genome research, vol 29, iss 4 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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