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Review
. 2024 Jul 18;25(14):7854.
doi: 10.3390/ijms25147854.

The Impact of Tobacco Smoking and Alcohol Consumption on the Development of Gastric Cancers

Waku Hatta  1 , Tomoyuki Koike  1 , Naoki Asano  1   2   3 , Yutaka Hatayama  1 , Yohei Ogata  1 , Masahiro Saito  1 , Xiaoyi Jin  1 , Kaname Uno  1 , Akira Imatani  1 , Atsushi Masamune  1
Affiliations
Review

The Impact of Tobacco Smoking and Alcohol Consumption on the Development of Gastric Cancers

Waku Hatta et al. Int J Mol Sci. .

Abstract

Chronic infection of Helicobacter pylori is considered the principal cause of gastric cancers, but evidence has accumulated regarding the impact of tobacco smoking and alcohol consumption on the development of gastric cancers. Several possible mechanisms, including the activation of nicotinic acetylcholine receptors, have been proposed for smoking-induced gastric carcinogenesis. On the other hand, local acetaldehyde exposure and ethanol-induced mucosal inflammation have been proposed as the mechanisms involved in the development of gastric cancers in heavy alcohol drinkers. In addition, genetic polymorphisms are also considered to play a pivotal role in smoking-related and alcohol-related gastric carcinogenesis. In this review, we will discuss the molecular mechanisms involved in the development of gastric cancers in relation to tobacco smoking and alcohol consumption.

Keywords: alcohol consumption; alcohol drinking; carcinogenesis; gastric cancer; gastric intestinal metaplasia; polymorphism; tobacco smoking.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Ethanol metabolism and its role in carcinogenesis. Ethanol, metabolized by ADH, CYP2E1, and, to a much lesser extent, by catalase, is further metabolized to harmless acetate by ALDH. SNPs of ADH1B, ADH1C, CYP2E1, and ALDH2 vary in ethanol and acetaldehyde exposure across individuals. Oral microbe, H. pylori, and the swollen oral microbe in the stomach, as well as the gastric mucosa itself possess ADH activity. Acetaldehyde promotes acetaldehyde adduct formation during ethanol metabolism, causing DNA adduct formation. Increased CYP2E1 activity causes the increased ROS generation. Both ADH and ALDH2 enzyme activity causes an increased NADH/NAD+ ratio. NADH is reoxidized to NAD+ in the mitochondria, causing further increased ROS generation. ROS-induced lipid peroxidation causes lipid peroxidation products, such as 4HNE and MDA, that interact with DNA bases to form DNA adducts. H. pylori, Helicobacter pylori; ADH, alcohol dehydrogenase; NAD, nicotinamide adenine dinucleotide; CYP2E1, cytochrome P450 2E1; ALDH, aldehyde dehydrogenase; AA, acetaldehyde; ROS, reactive oxygen species; SNPs, single nucleotide polymorphisms; 4HNE, trans-4-hydroxy-2-nonenal; MDA, malondialdehyde.
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References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Chen Y.C., Malfertheiner P., Yu H.T., Kuo C.L., Chang Y.Y., Meng F.T., Wu Y.X., Hsiao J.L., Chen M.J., Lin K.P., et al. Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022. Gastroenterology. 2024;166:605–619. doi: 10.1053/j.gastro.2023.12.022. - DOI - PubMed
    1. Ogata Y., Hatta W., Ohara Y., Koike T., Abe H., Saito M., Jin X., Kanno T., Uno K., Asano N., et al. Predictors of early and late mortality after the treatment for early gastric cancers. Dig. Endosc. 2022;34:816–825. doi: 10.1111/den.14172. - DOI - PubMed
    1. Probst A., Schneider A., Schaller T., Anthuber M., Ebigbo A., Messmann H. Endoscopic submucosal dissection for early gastric cancer: Are expanded resection criteria safe for Western patients? Endoscopy. 2017;49:855–865. doi: 10.1055/s-0043-110672. - DOI - PubMed
    1. Morais R., Libanio D., Dinis Ribeiro M., Ferreira A., Barreiro P., Bourke M.J., Gupta S., Amaro P., Kuttner Magalhaes R., Cecinato P., et al. Predicting residual neoplasia after a non-curative gastric ESD: Validation and modification of the eCura system in the Western setting: The W-eCura score. Gut. 2023;73:105–117. doi: 10.1136/gutjnl-2023-330804. - DOI - PubMed

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