Tobacco use is a major public health problem worldwide. Tobacco-related
cancers cause millions of deaths annually. Although several tobacco agents play a role in the
development of tumors, the potent effects of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
(NNK) and N'-nitrosonornicotine (NNN) are unique. Metabolically activated NNK and
NNN induce deleterious mutations in oncogenes and tumor suppression genes by forming
DNA adducts, which could be considered as tumor initiation. Meanwhile, the binding of
NNK and NNN to the nicotinic acetylcholine receptor promotes tumor growth by
enhancing and deregulating cell proliferation, survival, migration, and invasion, thereby
creating a microenvironment for tumor growth. These two unique aspects of NNK and
NNN synergistically induce cancers in tobacco-exposed individuals. This review will
discuss various types of tobacco products and tobacco-related cancers, as well as the
molecular mechanisms by which nitrosamines, such as NNK and NNN, induce cancer.