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Review
. 2021 Sep 11;13(9):3173.
doi: 10.3390/nu13093173.

Alcohol and Cancer: Epidemiology and Biological Mechanisms

Harriet Rumgay  1 , Neil Murphy  2 , Pietro Ferrari  2 , Isabelle Soerjomataram  1
Affiliations
Review

Alcohol and Cancer: Epidemiology and Biological Mechanisms

Harriet Rumgay et al. Nutrients. .

Abstract

Approximately 4% of cancers worldwide are caused by alcohol consumption. Drinking alcohol increases the risk of several cancer types, including cancers of the upper aerodigestive tract, liver, colorectum, and breast. In this review, we summarise the epidemiological evidence on alcohol and cancer risk and the mechanistic evidence of alcohol-mediated carcinogenesis. There are several mechanistic pathways by which the consumption of alcohol, as ethanol, is known to cause cancer, though some are still not fully understood. Ethanol's metabolite acetaldehyde can cause DNA damage and block DNA synthesis and repair, whilst both ethanol and acetaldehyde can disrupt DNA methylation. Ethanol can also induce inflammation and oxidative stress leading to lipid peroxidation and further DNA damage. One-carbon metabolism and folate levels are also impaired by ethanol. Other known mechanisms are discussed. Further understanding of the carcinogenic properties of alcohol and its metabolites will inform future research, but there is already a need for comprehensive alcohol control and cancer prevention strategies to reduce the burden of cancer attributable to alcohol.

Keywords: DNA damage; acetaldehyde; alcohol; cancer; carcinogenesis; inflammation; lipid metabolism; one carbon metabolism; oxidative stress.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Global number and proportion of cancer cases attributable to alcohol consumption according to cancer type. Source of alcohol-attributable cases: Rumgay and colleagues [1].
Figure 2
Figure 2
The dose-response relationship for the risk of cancer at different sites per 10 g/day increase in alcohol consumption. Source of relative risk estimates: WCRF Continuous Update Project [7]. RR = Relative risk; CI = Confidence interval. * Non-linear dose-response observed indicating threshold effect.
Figure 3
Figure 3
The dose-response relationship for the risk of cancer at different sites by three level of alcohol intake: light (up to 12.5 g/day), moderate (12.5 to 50 g/day), and heavy (more than 50 g/day). Source of relative risk estimates: Bagnardi and colleagues [8]. RR = Relative risk; CI = Confidence interval.
Figure 4
Figure 4
A simplification of the pathways by which alcohol, as ethanol, might drive carcinogenesis. The enzymes alcohol dehydrogenase (ADH), cytochrome P-450 2E1 (CYP2E1), and catalase metabolise ethanol to acetaldehyde; acetaldehyde dehydrogenase (ALDH) enzymes then metabolise acetaldehyde to acetate but common polymorphisms can reduce ALDH activity. Acetaldehyde forms DNA adducts causing mutations and blocking DNA synthesis and repair. Both ethanol and acetaldehyde can disrupt DNA methylation by inhibiting S-adenosyl-L-methionine (SAMe) synthesis and DNA methyltransferase (DNMT) activity, and ethanol can impair one-carbon metabolism. Cytochrome P-450 2E1 (CYP2E1) activity produces reactive oxygen species (ROS) leading to lipid peroxidation, metastasis, angiogenesis, and further formation of DNA adducts. Ethanol can also induce inflammation leading to production of ROS and their downstream effects. Retinoid metabolism and the normal function of the immune system are both impaired by ethanol, while ethanol may lead to increases in sex hormone levels, as well as dysbiosis of the microbiome and liver cirrhosis.
See this image and copyright information in PMC

References

    1. Rumgay H., Shield K., Charvat H., Ferrari P., Sornpaisarn B., Obot I., Islami F., Lemmens V.E.P.P., Rehm J., Soerjomataram I. Global burden of cancer in 2020 attributable to alcohol consumption: A population-based study. Lancet Oncol. 2021;22:1071–1080. doi: 10.1016/S1470-2045(21)00279-5. - DOI - PMC - PubMed
    1. Buykx P., Li J., Gavens L., Hooper L., Lovatt M., Gomes de Matos E., Meier P., Holmes J. Public awareness of the link between alcohol and cancer in England in 2015: A population-based survey. BMC Public Health. 2016;16:1194. doi: 10.1186/s12889-016-3855-6. - DOI - PMC - PubMed
    1. Manthey J., Shield K.D., Rylett M., Hasan O.S.M., Probst C., Rehm J. Global alcohol exposure between 1990 and 2017 and forecasts until 2030: A modelling study. Lancet. 2019;393:2493–2502. doi: 10.1016/S0140-6736(18)32744-2. - DOI - PubMed
    1. International Agency for Research on Cancer [(accessed on 20 June 2021)];IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 44. Alcohol Drinking. 1988 Volume 44 Available online: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Monographs-On-T....
    1. International Agency for Research on Cancer [(accessed on 20 June 2021)];IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 96. Alcohol Consumption and Ethyl Carbamate. 2010 Volume 96 Available online: https://publications.iarc.fr/Book-And-Report-Series/Iarc-Monographs-On-T.... - PMC - PubMed

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