Mutational signatures associated with tobacco smoking in human cancer.

Mutational signatures associated with tobacco smoking in human cancer.
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DOI:
10.1126/science.aag0299
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发表时间:
2016-11-04
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Stratton MR
Stratton MR
中科院分区:
其他
文献类型:
--
作者:
Alexandrov LB;Ju YS;Haase K;Van Loo P;Martincorena I;Nik-Zainal S;Totoki Y;Fujimoto A;Nakagawa H;Shibata T;Campbell PJ;Vineis P;Phillips DH;Stratton MR

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Tobacco smoking increases the risk of at least 17 classes of cancer. We analyzed somatic mutations and DNA methylation in 5,243 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 clock-like 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.
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