Mutational signatures associated with tobacco smoking in human cancer
Author(s)
Type
Journal Article
Abstract
Tobacco smoking increases the risk of at least 17 classes of human cancer. We analyzed somatic mutations and DNA methylation in 5243 cancers of types for which tobacco smoking confers an elevated risk. Smoking is associated with increased mutation burdens of multiple distinct mutational signatures, which contribute to different extents in different cancers. One of these signatures, mainly found in cancers derived from tissues directly exposed to tobacco smoke, is attributable to misreplication of DNA damage caused by tobacco carcinogens. Others likely reflect indirect activation of DNA editing by APOBEC cytidine deaminases and of an endogenous clocklike mutational process. Smoking is associated with limited differences in methylation. The results are consistent with the proposition that smoking increases cancer risk by increasing the somatic mutation load, although direct evidence for this mechanism is lacking in some smoking-related cancer types.
Date Issued
2016-11-04
Date Acceptance
2016-09-23
Citation
Science, 2016, 354 (6312), pp.618-622
Publisher
Springer
Start Page
618
End Page
622
Journal / Book Title
Science
Volume
354
Issue
6312
Copyright Statement
© 2016, American Association for the Advancement of Science.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000386869800049&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
LUNG-CANCER
PROTEIN ADDUCTS
HUMAN TISSUES
DNA
CARCINOGENS
LANDSCAPE
PATTERNS
EXPOSURE
HOTSPOTS
GENOMES
Publication Status
Published
Date Publish Online
2016-11-04