Title |
Mutational signatures associated with tobacco smoking in human cancer
|
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Published in |
Science, November 2016
|
DOI | 10.1126/science.aag0299 |
Pubmed ID | |
Authors |
Ludmil B Alexandrov, Young Seok Ju, Kerstin Haase, Peter Van Loo, Iñigo Martincorena, Serena Nik-Zainal, Yasushi Totoki, Akihiro Fujimoto, Hidewaki Nakagawa, Tatsuhiro Shibata, Peter J Campbell, Paolo Vineis, David H Phillips, Michael R Stratton |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 89 | 12% |
Spain | 79 | 10% |
Japan | 36 | 5% |
United Kingdom | 35 | 5% |
Canada | 18 | 2% |
France | 18 | 2% |
Turkey | 18 | 2% |
Mexico | 12 | 2% |
India | 10 | 1% |
Other | 109 | 14% |
Unknown | 340 | 45% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 582 | 76% |
Scientists | 123 | 16% |
Practitioners (doctors, other healthcare professionals) | 44 | 6% |
Science communicators (journalists, bloggers, editors) | 15 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 8 | <1% |
France | 3 | <1% |
United Kingdom | 3 | <1% |
Brazil | 2 | <1% |
Germany | 2 | <1% |
Uruguay | 1 | <1% |
Korea, Republic of | 1 | <1% |
Canada | 1 | <1% |
Denmark | 1 | <1% |
Other | 5 | <1% |
Unknown | 1023 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 189 | 18% |
Researcher | 186 | 18% |
Student > Bachelor | 134 | 13% |
Student > Master | 89 | 8% |
Other | 59 | 6% |
Other | 153 | 15% |
Unknown | 240 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 294 | 28% |
Agricultural and Biological Sciences | 166 | 16% |
Medicine and Dentistry | 152 | 14% |
Computer Science | 31 | 3% |
Nursing and Health Professions | 18 | 2% |
Other | 123 | 12% |
Unknown | 266 | 25% |