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

1. Alvin W.T. Ng2,3,4,
2. Maude Ardin1,
3. Mona I. Churchwell5,
4. Manuraj Pandey1,
5. Claire Renard1,
6. Stephanie Villar1,
7. Vincent Cahais6,
8. Alexis Robitaille7,
9. Liacine Bouaoun8,
10. Adriana Heguy9,
11. Kathryn Z. Guyton10,
12. Martha R. Stampfer11,
13. James McKay12,
14. Monica Hollstein1,13,14,
15. Magali Olivier1,
16. Steven G. Rozen2,3,4,
17. Frederick A. Beland5,
18. Michael Korenjak1 and
19. Jiri Zavadil1
20. 1Molecular Mechanisms and Biomarkers Group, International Agency for Research on Cancer, Lyon 69008, France;
21. 2Centre for Computational Biology, Duke–NUS Medical School, Singapore 169857, Singapore;
22. 3Program in Cancer and Stem Cell Biology, Duke–NUS Medical School, 169857, Singapore;
23. 4NUS Graduate School for Integrative Sciences and Engineering, Singapore 117456, Singapore;
24. 5Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079, USA;
25. 6Epigenetics Group, International Agency for Research on Cancer, Lyon 69008, France;
26. 7Infections and Cancer Biology Group, International Agency for Research on Cancer, Lyon 69008, France;
27. 8Environment and Radiation Section, International Agency for Research on Cancer, Lyon 69008, France;
28. 9Department of Pathology and Genome Technology Center, New York University, Langone Medical Center, New York, New York 10016, USA;
29. 10IARC Monographs Group, International Agency for Research on Cancer, Lyon 69008, France;
30. 11Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;
31. 12Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, Lyon 69008, France;
32. 13Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany;
33. 14Faculty of Medicine and Health, University of Leeds, LIGHT Laboratories, Leeds LS2 9JT, United Kingdom

• Corresponding authors: zavadilj{at}iarc.fr; korenjakm{at}iarc.fr

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.

Footnotes

• [Supplemental material is available for this article.]

• Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.242453.118.

• Freely available online through the Genome Research Open Access option.

• Received July 31, 2018.

• Accepted February 1, 2019.

• © 2019 Zhivagui et al.; Published by Cold Spring Harbor Laboratory Press

This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.