Paper - Review

DOI: 10.1126/science.aag0299

Abstract

Tobacco smoking
→ increase the risk
← of at least 17 classes of human cancer

Analyzed → 1⃣ somatic mutations 2⃣ DNA methylation
← in 5K cancers of types
← for which tobacco smoking confers an elevated risk

Smoking → associated
→ with increased mutation burdens ← of multiple distinct mutational signatures
← which contribute to different extents ← in different cancers

Mainly found in cancers
← derived from tissues ← directly exposed to tobacco smoke
→ is attributable → to mis-replication of DNA damage
← caused by tobacco carcinogens

∴ Others → reflect
1⃣ indirect activation of DNA editing ← by APOBEC cytidine deaminases
2⃣ indirect activation of an endogenous clocklike mutation process

Smoking is associated
← with limited differences ← in methylation

Smoking
→ increases cancer risk ← by increasing the somatic mutation load

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