Mutational signatures associated with tobacco smoking in human cancer

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
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Issue Date
2016-11
Language
English
Keywords

LUNG-CANCER; PROTEIN ADDUCTS; HUMAN TISSUES; DNA; CARCINOGENS; LANDSCAPE; PATTERNS; EXPOSURE; HOTSPOTS; GENOMES

Citation

SCIENCE, v.354, no.6312, pp.618 - 622

ISSN
0036-8075
DOI
10.1126/science.aag0299
URI
http://hdl.handle.net/10203/214601
Appears in Collection
MSE-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
  • Hit : 80
  • Download : 0
  • Cited 0 times in thomson ci
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡClick to seewebofscience_button
⊙ Cited 4 items in WoSClick to see citing articles inrecords_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0