Using the data from All of Us does come with some limitations, they acknowledged, including that cancer diagnoses were self-reported and couldn’t be verified in every case. And because of the study’s nature, it can also create certain “biases” in the data that may affect its accuracy or how relevant it is to the larger population of people with cancer and long-term survivors. Public health campaigns about the cancer risk posed by alcohol in England and Australia have been effective at raising awareness with their target audiences. 2The exception to this is a study in Russia indicating an inverse association between alcohol consumption and mortality (Zaridze et al. 2009). Overall, very few studies have addressed the role of and interaction among alcohol, cancer, and the immune system once the cancer is established. It is important to understand these interactions, however, because many alcoholics have immune deficiencies and because a competent immune system is important to the success of many conventional drug therapies for cancer.

Does the type of alcohol matter?

The oxidative metabolism of ethanol to acetaldehyde by alcohol dehydrogenase (ADH), and at high blood alcohol concentrations by ethanol-inducible cytochrome P4502E1 (CYP2E1) and catalase, also appears to play a role in carcinogenesis (10). The induction of CYP2E1 can activate procarcinogens, leading to the formation of reactive oxygen species which react with cellular lipids to form mutagenic DNA adducts, and DNA damage (10). Acetaldehyde can interfere with DNA synthesis and repair, form DNA-adducts, and cause cytotoxicity and mutagenicity (10). 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. Ethanol can also contribute to carcinogenesis through the induction of oxidative stress which is recognised as a key determinant of disease initiation [26].

1. The participants were tracked for a median period of 11 years through linkage to health insurance records and death registers.
2. (1) Cells that escape from a primary solid tumor invade into the surrounding normal tissue by passing through the basement membrane and extracellular matrix (ECM).
3. While studies have provided evidence on alcohol’s carcinogenic potential, further understanding of alcohol’s pathways to cancer development will inform the direction of future research.
4. Furthermore, DNA damage can occur through exposure to acetaldehyde and ROS which are both produced through CYP2E1 activity, with acetaldehyde also a product of ADH activity.

Methods Used for the Meta-Analysis

This review relates the amount and duration of alcohol intake in humans and in animal models of cancer to tumor growth, angiogenesis, invasion, metastasis, immune response, and host survival in specific types and subtypes of cancer. Although there is more information in animal models of cancer, many aspects still are ill defined. More research is needed to define the mechanisms that underlie the role of alcohol on cancer progression in both animals and humans. Activation of the immune system can play a positive role in keeping cancer under control, but this also can facilitate cancer progression.

Statistical Methods Used in the Meta-Analysis

Acetaldehyde can inhibit the activity of DNA methyltransferase (DNMT) which is essential for normal DNA methylation; acetaldehyde can also reduce DNMT mRNA levels leading to less production of DNMT [25]. Acetaldehyde and ethanol may also inhibit the synthesis of S-adenosyl-L-methionine (SAMe) which is essential to DNA methylation [21]. While no alcohol is best, women who choose to drink should have no more than one drink a day, and men no more than two drinks a day.

Finally, evidence from animal models and human studies suggests that appropriately combined chemotherapy and immunotherapy may be more beneficial than either therapeutic approach alone (Ardiani et al. 2013; Shi et al. 2014; van Meir et al. 2014; Wang et al. 2014). Despite substantial epidemiological and mechanistic evidence on alcohol and cancer, several knowledge gaps remain that if filled could improve estimates of the burden of alcohol-attributable alcohol use disorder cancers, and inform tailord interventions to reduce consumption. Many individuals of East Asian descent carry a version of the gene for ADH that codes for a “superactive” form of the enzyme. 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).

How does the combination of alcohol and tobacco affect cancer risk?

We have only covered carcinogenesis in this review, but alcohol likely alters, through these pathways and others, other functions in the body which render it more susceptible to other diseases and injuries, as discussed in other articles in this Special Issue. More than 30 years ago, in 1988, the International Agency for Research on Cancer (IARC) classified alcoholic beverages as a group 1 carcinogen, the most severe classification [4]. The IARC Monographs program aims to classify cancerous agents according to the strength of the available epidemiological and experimental evidence.

While studies have provided evidence on alcohol’s carcinogenic potential, further understanding of alcohol’s pathways to cancer development will inform the direction of future research. This information is useful to corroborate existing evidence, develop chemoprevention strategies, and could improve cancer therapy, but there is already a wealth of evidence to support the need for further alcohol control and cancer prevention efforts. 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. 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].

Learning about the downsides of mammograms did not discourage women from wanting to get the test at some point, the study showed. The health department recommends seeing a doctor if attempting to reduce or quit alcohol. “Zero alcohol ads are reaching young people through several avenues, including popular social media platforms like Instagram and TikTok,” he said. “Obviously there are other factors that doctors and patients consider when choosing drugs for treating diabetes,” Basen-Engquist says, but patients taking insulin may want to discuss with their physician whether they might gain additional benefit from a GLP-1 medication. Get instant access to members-only products and hundreds of discounts, a free second membership, and a subscription to AARP The Magazine.

A large body of literature indicates that alcohol consumption modulates many aspects of the innate and adaptive immune systems. Alcohol originally was described as immunosuppressive, and numerous studies support the immunosuppressive aspects of alcohol consumption on the innate and adaptive immune systems. However, it also is well documented that chronic alcohol administration can activate the immune system—especially dendritic cells, T cells, and NKT cells—in experimental animals as well as humans (Cook et al. 1991; Laso et al. 2007; Song et al. 2002; Zhang and Meadows 2005).

Yirmiya and colleagues (1992) also administered ethanol in a liquid diet for 2 weeks before and 3 weeks after tumor inoculation and found that lung metastases were increased. Gu and colleagues (2005) assessed the effects of alcohol on human HT1080 colon cancer cells in a chick embryo model, focusing on variables related to the blood supply of the tumor. One of the variables analyzed was the expression of vascular endothelial growth factor (VEGF)—a growth factor that promotes blood vessel formation (i.e., is proangiogenic) and enhances tumor vascularization. Exposure of isolated tumor cells to 10 mM and 20 mM ethanol for 19 hours also increased VEGF mRNA and protein expression.

To address these unknowns, researchers from Oxford Population Health, Peking University and the Chinese Academy of Medical Sciences, Beijing, used a genetic approach by investigating gene variants linked to lower alcohol consumption in Asian populations. 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. Continued research into the detrimental and beneficial effects of alcohol in human cancer patients and animal models of cancer is a key factor to understanding the complex interactions that affect tumor progression and survival, particularly in the context of alcohol use. This research has a strong potential to discover new immunotherapy and epigenetic approaches to cancer treatment as well as treatment of other alcohol-induced diseases.

After 8 weeks of ethanol administration or regular food, the mice were implanted with the tumor cells and also received one injection of the anti-CD4 antibody. Mice in the non–ethanol-fed control group injected with one dose of anti-CD4 antibody initially developed large tumors at 6 weeks, which significantly regressed thereafter. Compared with these control animals, the ethanol-fed mice exhibited significantly larger alcohol and diabetes tumors at 6 weeks as well as a diminished ability to decrease their tumor size at 13 weeks. The findings suggest that this difference in the ability of the ethanol-fed mice to reduce their tumor burden results from an impaired immune system caused by chronic alcohol intake. Drinking alcohol increases the risk of several cancer types, including cancers of the upper aerodigestive tract, liver, colorectum, and breast.

The study determined that all cervical and Kaposi sarcoma cancers were caused by elevated risk factors that had the potential to be modified, as well as more than 50% in 19 of the 30 cancer typesat which researchers looked. Trailing some way behind were being overweight with a population attributable fraction of 7% was excess body weight; alcohol consumption at 5.4%; and UV radiation exposure and physical salvia drug overview inactivity at 4.6% and 3.1%, respectively. In the meantime, experts say, you should talk with your doctor about how much you drink so that you can better understand the risks. Many people aren’t having this conversation about alcohol with health care providers. Indeed, one study found that more than a quarter of older adults who used alcohol were not asked about their drinking by their physician.

The results remained the same when the data were adjusted for other cancer risk factors, such as smoking, diet, physical activity, body mass and family history of cancer. There likely are additional cancers linked to drinking alcohol, Dr. Orlow says, but more well-designed studies (epidemiological and other) are needed to prove that alcohol is a contributing risk factor. Because cancer risk increases with the amount of ethanol consumed, all alcoholic beverages pose a risk.

Estrogen pellets were implanted after 19 weeks of alcohol consumption, and tumors were implanted after 22 weeks. The results on tumor growth were similar to those obtained by Hong and colleagues (2011), with the high-fat diet and alcohol promoting tumor growth and estrogen suppressing it. Tumor growth was greatly inhibited in the mice receiving a high-fat diet as well as estrogen supplements.