Furthermore, alcohol consumption reduced the overall numbers of B cells in the spleen, although it did not affect all types of B cells equally. Thus, there was no effect on splenic follicular B cells, whereas the number of immature T1 B (CD19+CD93+CD23−) cells increased and the number of marginal zone B cells (CD19+CD1dhiCD21hi) decreased. Increased ethanol consumption can induce microbial dysbiosis and bacterial overgrowth in the intestine 20. This heightened bacterial presence may compromise the intestinal barrier resulting in ”gut leakiness” where the permeability of the intestinal lumen is high enough such that bacterial products including lipopolysaccharides and peptidoglycan move from the intestine into the blood 20,45. Once in the blood these bacterial products easily reach the liver where a variety of cells are activated (endothelial cells, liver macrophages, stellate cells and hepatocytes) producing a chronic inflammatory environment 33, which may confer an increased risk of liver cancer 46.
3. Increased Inflammation
There is mounting evidence that alcohol can negatively affect one-carbon metabolism which is essential for DNA methylation and DNA synthesis 25. Ethanol and acetaldehyde can reduce the activity of enzymes involved in one-carbon metabolism that regulate DNA methylation, namely methionine synthase, methionine adenosyl transferase and DNMT, thus dysregulating epigenetic patterns and resulting in DNA hypomethylation 20. Both acetaldehyde and ethanol can impact DNA methylation which may lead to changes in the expression of oncogenes and tumour-suppressor genes 21.
Studying the Impact of Total Diet on Cancer Risk
It can also increase blood levels of estrogen, a sex hormone linked to breast cancer, and make the carcinogens found in tobacco smoke easier for the body to absorb. Ethanol–the principal form of alcohol in alcoholic beverages–is a widely-used, psychoactive, and dependence-producing substance. Alcohol research and control efforts supported by multiple governmental and non-governmental organizations (NGOs) internationally have found that the public health impact of harmful alcohol consumption is substantial. In 2016, it resulted in an estimated 5.1% of the global burden of disease and injury, and 5.3% of deaths (1). A large meta-analysis of 23 health outcomes showed that the number of daily alcohol beverages that minimized harm overall was 0 (95% uncertainty interval 0.00–0.08) (2).
The higher ethanol doses (i.e., 2.5 g/kg and 3.5 g/kg) significantly increased the number of lung metastases, whereas the lowest dose (1.5 g/kg) did not. Administration of naltrexone, an opioid receptor antagonist used to group activities for recovery treat alcohol dependence, did not modify the alcohol-related increase in metastasis. Thus, in a related study these researchers found that administration of 2.5 g/kg ethanol 24 hours before or after tumor inoculation did not affect lung metastasis (Ben-Eliyahu et al. 1996).
How does alcohol affect the risk of cancer?
Despite the large body of scientific evidence on the topic, the full cancer burden due to alcohol remains uncertain because for many cancer (sub)types associations with risk and survivorship are inconsistent or there are few studies. Moreover, most U.S. adults are unaware of the alcohol-cancer link (7), and the interrelationships of alcohol control regulations and cancer risk is unclear. Few studies have specifically examined the interaction between alcohol and the immune response in cancer patients or in experimental animals implanted with cancer cells.
Drinking alcohol even at lower levels of intake can increase the risk of cancer and we previously estimated that over 100,000 cases of cancer in 2020 were caused by light and moderate drinking of the equivalent of around one or two alcoholic drinks per day 1. Despite this, there is low public awareness of the causal link between alcohol and cancer and alcohol use is growing in several regions of the world 2,3. The contribution of NK how to wean off alcohol cells to the inhibition of metastasis was evaluated in mice consuming 10 percent or 20 percent w/v ethanol for 4 weeks (Meadows et al. 1993a). Whereas consumption of 10 percent ethanol did not alter the NK cells’ ability to destroy other cells (i.e., decrease cytolytic activity), animals consuming 20 percent ethanol showed decreased NK cytolytic activity. And although experimental stimulation of NK cells could enhance their cytolytic activity 4.3-fold in the ethanol-drinking animals, compared with 2.6-fold in the control animals, overall cytolytic activity still was lower in the ethanol group than in the control group. Treatment of mice with an antibody against NK cells (i.e., anti-NK1.1 antibody) markedly decreased NK-cell cytolytic activity in both water- and ethanol-drinking animals.
- Similarly, incubation for 48 hours in 0.1 percent and 0.2 percent w/v ethanol stimulated invasion of estrogen receptor–negative SKBR3 and estrogen receptor–positive BT474 breast cancer cells.
- The higher ethanol doses (i.e., 2.5 g/kg and 3.5 g/kg) significantly increased the number of lung metastases, whereas the lowest dose (1.5 g/kg) did not.
- A further updated MR study using UK Biobank data did not find an association between alcohol exposure and cancer of any site, though they noted limitations of a lack of precision in their analyses due to low variance explained by the single nucleotide polymorphisms 18.
- The effect of alcohol on one-carbon metabolism and folate might also be important in colorectal cancer development 20.
Publication types
Tumors also release factors that can directly or indirectly suppress antitumor immune responses, thus facilitating angiogenesis, invasion of surrounding tissues, and metastasis to distant sites in the body (for a general review, see Jung 2011). (For more information on the processes involved in tumor metastasis, see the sidebar.) The following sections will review the role of alcohol in cancer growth and progression, both in humans and in animal models. 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.
But it has been difficult to establish whether alcohol directly causes cancer, what does being roofied feel like or if it is linked to possible confounding factors (such as smoking and diet) that could generate biased results. It was also unclear whether alcohol is linked to other types of cancer, including lung and stomach cancers. There is further hypothesis that alcohol consumption might activate the pathways of other carcinogenic agents; this could occur through the alcohol-induced activity of CYP2E1 which may metabolise pro-carcinogens in tobacco smoke and industrial chemicals 21. It is also possible that ethanol might aid these carcinogens to penetrate cells, especially those of the mucosa of the upper aerodigestive tract 21,48, where tobacco and alcohol have a synergistic effect on the risk of cancer 11,12.
ROS can further promote cell proliferation and metastasis by interfering with mitogen-activated protein kinase signalling pathways and upregulating vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) which can stimulate angiogenesis 31. In HCC tissue samples from alcohol drinkers, ROS accumulation and increased synthesis of VEGF, MCP-1 and NF-κB were observed, indicating alcohol-driven promotion and progression of HCC 32. The future potential of MR studies is yet to be discovered but disclosing potential sources of biases and confounding in observational studies is necessary to obtain robust estimates of the causal relationship between alcohol consumption and cancer risk. A related study using the same alcohol-feeding regimen confirmed alcohol’s effects on growth and angiogenesis of E0771 inoculated into other female C57BL/6 mice (Lu et al. 2014). In that study, a molecule that can inhibit VEGF receptor 2 blocked alcohol’s stimulatory effect on tumor growth, indicating that alcohol acts via a VEGF pathway. 1In estrogen-positive breast cancer, the cancer cells carry the estrogen receptor and depend on estrogen for growth.