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Smokeless tobacco and cigarette smoking: chemical mechanisms and cancer prevention

Nature Reviews Cancer volume 22, pages 143–155 (2022)Cite this article

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Abstract

Tobacco products present a deadly combination of nicotine addiction and carcinogen exposure resulting in millions of cancer deaths per year worldwide. A plethora of smokeless tobacco products lead to unacceptable exposure to multiple carcinogens, including the tobacco-specific nitrosamine N′-nitrosonornicotine, a likely cause of the commonly occurring oral cavity cancers observed particularly in South-East Asian countries. Cigarettes continue to deliver a large number of carcinogens, including tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons and volatile organic compounds. The multiple carcinogens in cigarette smoke are responsible for the complex mutations observed in critical cancer genes. The exposure of smokeless tobacco users and smokers to carcinogens and toxicants can now be monitored by urinary and DNA adduct biomarkers that may be able to identify those individuals at highest risk of cancer so that effective cancer prevention interventions can be initiated. Regulation of the levels of carcinogens, toxicants and nicotine in tobacco products and evidence-based tobacco control efforts are now recognized as established pathways to preventing tobacco related cancer.

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Fig. 1: Overall established scheme relating smokeless tobacco use and cigarette smoking, as driven by nicotine addiction, to cancer.
Fig. 2: Structures of NNN, NNK and NNAL.
Fig. 3: Metabolism of (S)-nicotine and (S)-NNN by 5′-hydroxylation.

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Acknowledgements

The authors’ research is supported by US National Cancer Institute grants P01 CA-138338 (S.S.H.), R01 CA-081301 (S.S.H.) and P01 CA-217806 (D.K.H.) and by US National Institute on Drug Abuse grant U54 DA-031659 (D.K.H.). The studies reported here were accomplished by an outstanding team of researchers. We thank all team members for their contributions.

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  1. Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Stephen S. Hecht & Dorothy K. Hatsukami

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Both authors researched data for the article. S.S.H. wrote the sections on carcinogens and their effects, and D.K.H. wrote the sections on regulating tobacco products.

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Correspondence to Stephen S. Hecht.

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Glossary

DNA adducts

Compounds formed by the reaction of DNA bases with certain electrophilic intermediates generated during metabolism, or with inherently reactive substances.

Odds ratio

A statistic that explains the association between two events.

Areca nut

The seed of the areca palm, which grows in South-East Asia; it is a common constituent of a quid known as paan, which is chewed by millions of people in the region.

Agronomics

The branch of economics dealing with the distribution, management and productivity of land.

Apurinic sites

Sites in DNA lacking the usual guanine or adenine bases. The sites can be formed when certain relatively unstable DNA adducts, such as 7-methyldeoxyguanosine, lose their purine base (in this case 7-methylguanine) due to spontaneous decomposition or hydrolysis.

Creatinine

A waste product from normal metabolism that is commonly used as a denominator in biomarker studies.

Advance notice of proposed rulemaking

(ANPRM). A document that an agency such as the US Food and Drug Administration may choose to issue before it is ready to issue a notice of proposed rulemaking. It is the first public step in the notice and comment rulemaking process, and the comments received could affect the final rule making process.

Cigarette filter ventilation

The practice of incorporating holes near the cigarette filter to allow air to mix with the smoke stream, leading to overall lower constituent concentrations. It is a defective design because the holes may be blocked during smoking but not during machine measurement of smoke constituents.

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Hecht, S.S., Hatsukami, D.K. Smokeless tobacco and cigarette smoking: chemical mechanisms and cancer prevention. Nat Rev Cancer 22, 143–155 (2022). https://doi.org/10.1038/s41568-021-00423-4

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