Author: John Carter

Alcohol Use and Cancer American Cancer Society

Inflammation is a key pathway to cancer progression at several sites and is enhanced by alcohol use. Chronic alcohol consumption can recruit specific white blood cells (monocytes and macrophages) to the tumour microenvironment. These white blood cells produce pro-inflammatory cytokines, such as tumour necrosis factor α (TNF-α) and the interleukins IL-1, IL-6, and IL-8 [31,33], which activate oxidant-generating enzymes leading to downstream formation of ROS [30]. People who said they had searched for cancer information were more likely to know about the cancer risks posed by drinking beer and by drinking liquor than those who did not. But awareness of the risk from drinking wine was similar in both those who had and hadn’t sought cancer information. The fact that drinking alcohol can cause cancer has received increasing attention in the past few years.

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]. Increased ethanol consumption can induce microbial dysbiosis and bacterial overgrowth in the intestine [20]. Microbiota in the oral cavity metabolise ethanol to acetaldehyde by the enzyme catalase.

We have discussed evidence on mechanistic and epidemiological research in the field, and this information must be used to decrease the burden of cancers, as well as other diseases and injuries, attributable to alcohol. 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.

Retinoids are important regulators against carcinogenesis as they can induce cell growth, cell differentiation, and apoptosis [31]. Alcohol can alter retinoid metabolism by inhibiting the oxidation of vitamin A to retinoic acid [21]. Alcohol increases CYP2E1 activity (Section 3.2) which also functions to metabolise retinoic acid resulting in the production of toxic metabolites [21]. This increased toxicity of retinoids may explain the observation of excess lung cancer risk in smokers who took β-carotene supplements and consumed 11 g or more of ethanol per day in the α-tocopherol, β-carotene cancer prevention study (ATBC trial) study [21].

4. Disruption to One-Carbon Metabolism and Folate Absorption

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. 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.

1. For example, alcohol – even in very small amounts – can irritate mouth sores caused by some cancer treatments, and can even make them worse.
2. Alcohol and its metabolite acetaldehyde can drive cancer development through several pathways.
3. Given the study’s findings, “there’s also a need to better understand why so many cancer survivors have such high alcohol consumption,” she continued.
4. According to the study’s findings, male long-term survivors and younger people being treated for cancer were among those who were particularly likely to be heavy or frequent drinkers.

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.

Can people’s genes affect their risk of alcohol-related cancers?

Cells that are damaged by the alcohol may try to repair themselves, which could lead to DNA changes that can be a step toward cancer. One method which might overcome some of the limitations in observational studies is Mendelian randomisation (MR), which uses genetic variants to explore the causal relationship between exposure and disease outcome. Assuming that analyses are conducted appropriately, due to the random distribution of these genetic variants at birth, MR studies should be less prone to conventional confounding and reverse causality. Alcoholic beverages may also contain a variety of carcinogenic contaminants that are introduced during fermentation and production, such as nitrosamines, asbestos fibers, phenols, and hydrocarbons. That said, Dr. DuVall continued, high alcohol use in AYAs who have or had cancer is not necessarily surprising. Launched in 2018, All of Us captures information on participants’ lifestyle and other behaviors and personal background via comprehensive surveys.

There are also concerns around reverse causality, with the reference categories of alcohol non-drinkers possibly including former drinkers who still have an elevated risk of cancer. There are other concerns over the accuracy of recording of alcohol exposure data where bias may be incorporated through non-participation of heavy drinkers in health studies, and under-reporting of alcohol consumption by the study subjects. The World Cancer Research Fund (WCRF) also conducts classification of physical and dietary components and their potential cancerous effects as part of their Continuous Update Project. The WCRF base their conclusions on the quality of epidemiological evidence and carry out meta-analyses of the association with cancer risk.

More than just light drinking

But the potential threat it poses to people with cancer and longer-term survivors has largely been overlooked, explained Tanya Agurs-Collins, Ph.D., of the Behavioral Research Program in NCI’s Division of Cancer Control and Population Sciences. In addition to its involvement in downstream ROS-producing pathways, it is hypothesised that IL-8 contributes to further accumulation of white blood cells (neutrophils, specifically) in the liver leading to acute inflammation. Elevated IL-8 levels have been found in patients with acute liver injury such as alcoholic hepatitis [34]. Additionally, the cytokine IL-6 stimulates production of the anti-apoptotic protein Mcl-1, thus avoiding cell death and exposing the cell to further DNA damage [35].

Most evidence suggests that it is the ethanol that increases the risk, not other things in the drink. Educating the public about the cancer risk from drinking alcohol, regardless of the beverage type, is especially urgent given the increase in drinking during the COVID-19 pandemic, Dr. Klein said. Numerous changes need to be made to raise public awareness of the fact that drinking alcohol raises the risk of several types of cancer.

But it is not clear whether alcohol use after treatment might increase the risk of these cancers coming back (recurring). For example, alcohol can increase the levels of estrogens in the body, which might increase the risk for breast cancer recurrence. But for some types of cancer, most notably breast cancer, consuming even small amounts of alcohol can increase risk.

The association between alcohol drinking and risk of other cancer types has been studied but without sufficient evidence to be classified in the IARC monographs or WCRF Continuous Update Project. A positive association with lung cancer was only found for heavy drinkers in Bagnardi and colleagues’ meta-analysis, but this was probably due to residual confounding from smoking because alcohol use did not increase the risk of lung cancer among non-smokers [8]. Little evidence of an association between alcohol consumption and gallbladder cancer was found in the WCRF Continuous Update Project, but Bagnardi and colleagues found an excess risk of gallbladder cancer among heavy drinkers (RR 2.64 (95% CI 1.62–4.30)). WCRF found an elevated risk of malignant melanoma per 10 g alcohol per day (RR 1.08 (95% CI 1.03–1.13)), but no effect on basal cell carcinoma (RR 1.04 (95% CI 0.99–1.10)) or squamous cell carcinoma (RR 1.03 (95% CI 0.97–1.09)) risk [7]. An increased risk of prostate cancer was observed for light and moderate drinking in Bagnardi and colleagues’ meta-analysis but not in the dose-response analysis of one drink per day by WCRF [7,8]. The most common histological subtype of liver cancer is hepatocellular carcinoma (HCC) and around 154,700 cases of HCC in 2020 were attributable to alcohol consumption [1].

Effects on body weight

The first mutation is a loss-of-function mutation in the gene for the enzyme aldehyde dehydrogenase 2 (ALDH2). Given the study’s findings, “there’s also a need to better understand why so many cancer survivors have such high alcohol consumption,” she continued. “The high prevalence of cancer survivors engaged in hazardous drinking highlights the need for immediate interventions,” they wrote. More research is needed to better understand alcohol use among people with cancer, the study team wrote. Of the participants with a history of cancer, nearly 1,800 were in active treatment for cancer at the time they completed the initial survey. In fact, there are likely several different ways it can raise risk, and this might depend on the type of cancer.

This superactive ADH enzyme speeds the conversion of alcohol (ethanol) to toxic acetaldehyde. Among people of Japanese descent, those who have this form of ADH have a higher risk of pancreatic cancer than those with the more common form of ADH (30). The mechanisms by which alcohol consumption may decrease the risks of some cancers are not understood and may be indirect. These amounts are used by public health experts in developing health guidelines about alcohol consumption and to provide a way for people to compare the amounts of alcohol they consume. However, they may not reflect the typical serving sizes people may encounter in daily life. Greater collaboration with other specialties and clinicians who regularly interact with people with cancer, such as oncology nurses, to develop ways to reduce risky drinking behaviors will be needed moving forward, Dr. Agurs-Collins said.

And little has been done to understand how to help those who are heavier drinkers change their behavior. According to the American Cancer Society Guideline for Diet and Physical Activity for Cancer Prevention, it is best not to drink alcohol. People who choose to drink alcohol should limit their intake to no more than 2 drinks per day for men and 1 drink a day for women. In pregnant women, alcohol use, especially heavy drinking, may lead to birth defects or other problems with the fetus. Ethanol is the type of alcohol found in alcoholic drinks, whether they are beers, wines, liquors (distilled spirits), or other drinks.