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Review
. 2023 Dec 20;11(12):410.
doi: 10.21037/atm-23-1710. Epub 2023 Dec 4.

A systematic review of preclinical studies evaluating the association between nicotine and the initiation and progression of cancer

Mimi M Kim  1 , Isabella Steffensen  1 , Red Thaddeus D Miguel  1 , Tanja Babic  1 , Aubrey D Johnson  2 , Ryan Potts  2 , Christopher S Junker  2
Affiliations
Review

A systematic review of preclinical studies evaluating the association between nicotine and the initiation and progression of cancer

Mimi M Kim et al. Ann Transl Med. .

Abstract

Background: The association between cigarette smoking and the increased risk of many cancers is well established. Conversely, epidemiological studies of smokeless tobacco demonstrate decreased risk, or no elevated risk, of certain cancers versus smoking. However, it is unclear what role, if any, nicotine plays in these associations. The objective of this systematic review was to synthesize the available evidence from preclinical studies that examined the potential association between nicotine and the initiation and/or progression of cancer.

Methods: MEDLINE, Embase, PsychInfo, and Cochrane Database of Systematic Reviews were searched for articles published from inception until February 13, 2022. Studies were eligible for inclusion if they evaluated animal cancer or tumor models, compared nicotine and non-nicotine groups, and evaluated measures of cancer initiation or progression.

Results: Among 1,137 identified articles, 61 were included in qualitative synthesis. Twelve studies reported data on tumor initiation, and 54 studies reported data on tumor progression. The majority of the tumor initiation studies did not identify an association between nicotine exposure and an increased risk of spontaneous tumor initiation. Results of tumor progression studies were inconsistent and varied across the reported measures, cancer type being evaluated, and animal cancer model used. Overall, the quality of reporting was poor, with many studies not demonstrating a high level of internal and/or external validity.

Conclusions: In conclusion, although animal models have provided invaluable data for human health risk assessments of chemical exposures, the heterogeneity across the studies included in this systematic review make the interpretation and generalizability of the results difficult.

Keywords: Cancer; nicotine; preclinical; tumor initiation; tumor progression.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-23-1710/coif). M.M.K. serviced as a full-time employee of Reynolds American until March 31, 2023 and received restricted company shares as part of the company benefits package. In April of 2023, M.M.K. began a new full-time position at Thera-Business. Thera-Business Inc. has provided regulatory science consulting services to RAI Services Company, a wholly-owned subsidiary of British American Tobacco. I.S. is an employee of Thera-Business. Thera-Business Inc. has provided consulting services to RAI Services Company, a wholly-owned subsidiary of British American Tobacco. R.T.D.M. is an employee of Thera-Business. Thera-Business Inc. has provided consulting services to RAI Services Company, a wholly-owned subsidiary of British American Tobacco. A.D.J. is a full-time employee of Reynolds American. R.P. is a full-time employee of Reynolds American and receives restricted shares as a part of the benefits package. Reynolds American is a sponsor that has paid Thera-Business for contracted regulatory research services. C.S.J. is a full-time employee of Reynolds American, and receive restricted shares as a part of the benefits package. Reynolds American is a sponsor that has paid Thera-Business for contracted regulatory research services. T.B. has no conflicts of interest to declare.

Figures

Figure 1
Figure 1
PRISMA flow diagram.
Figure 2
Figure 2
Included studies by publication year.
Figure 3
Figure 3
Included studies by country/region of publication.
See this image and copyright information in PMC

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