articleScienceNov 3, 2016GREEN OA

Mutational signatures associated with tobacco smoking in human cancer

LBLudmil B. AlexandrovYSYoung Seok JuKHKerstin HaasePVPeter Van LooSMSancha Martin

Los Alamos National Laboratory · University of New Mexico · +15 more institutions

PubMed
Indexed incrossrefpubmed

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…

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Topics & keywords

Topics
Keywords
  • Tobacco use
  • Cancer
  • Genetics
  • Biology
  • Tobacco smoke
  • Environmental health
  • Computational biology
  • Medicine
UN Sustainable Development Goals
  • Good health and well-being
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