Another study found that using multiple and diverse information sources can reduce alcohol use intentions as compared to reliance on a single source (41). A high proportion of American adults, both drinkers and non-drinkers (35), are unaware of the association between alcohol consumption and cancer risk. However, the fact that most Americans are unaware of the association suggests effective evidence-based strategies are needed to increase awareness, encourage informed decision making, modify health behavior, and develop policies to reduce consumption. However, some individuals with the defective form of ALDH2 can become tolerant to the unpleasant effects of acetaldehyde and consume large amounts of alcohol.
Studying the Impact of Total Diet on Cancer Risk
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]. Following epidemiological evidence of the link between alcohol use and risk of cancer at multiple sites, several pathways have been investigated to explain the carcinogenic effects of alcohol. Here, we discuss the key mechanisms linking alcohol consumption to carcinogenesis, which are depicted in Figure 4.
Site-of-care shifts: Healthcare’s $50B opportunity
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. Participants can also allow access to their electronic health records (with all identifying information removed), providing important insights on treatments received and other relevant health information. But the All of Us study, Dr. Cao and her colleagues explained, offered a unique opportunity to take a robust look at people in these groups in the United States. But results from a new study suggest that this information may not be reaching people who fall into either of these two categories. 4Epithelial mesenchymal transition is a process whereby epithelial cells lose their innate cellular polarity and cell–cell adhesive properties to become mesenchymal cells, which lack polarity and have the ability to migrate and to invade through tissues.
Alcohol drinking disorders can lead to liver fibrosis and cirrhosis (12)–an established cause of liver cancer. 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. The study also found that people who believed drinking alcohol increased the risk of heart disease were more aware of the alcohol–cancer risk than those who were unsure or believed drinking lowered the effect on heart risk.
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]. In addition to associations from epidemiological studies, multiple mechanistic pathways through which alcohol can cause cancer have been proposed.
The study found that the ethanol group exhibited higher primary tumor growth rates, increased final tumor weights, and a twofold increase in lung metastases compared with the water-drinking control group. Immunohistochemical analyses of the mammary tumor tissues also showed a higher density of tiny blood vessels in the ethanol group, indicating that ethanol promoted tumor angiogenesis. MCP-1 plays an important role in suppressing antitumor immune functions and facilitating tumor metastasis (Kudo-Saito et al. 2013), indicating another mechanism through which alcohol could promote breast cancer progression. 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. Positive associations have been reported in some meta-analyses; for example, a 3% increase in lung cancer risk was observed per 10 g alcohol per day in the WCRF meta-analysis based on 28 studies (RR 1.03 (95% CI 1.01–1.04)) after excluding studies which did not control for smoking [7]. 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].
Furthermore, metastases were significantly reduced in the 2-week and 8-week ethanol groups but not in the 4-week and 5-week groups. Administration of ethanol for 2 weeks after tumor inoculation affected neither tumor growth nor metastasis. Exposure to ethanol before but not after tumor injection significantly decreased the tumor cell number.
Alcohol and Cancer: Existing Knowledge and Evidence Gaps Across the Cancer Continuum
I think there is a chunk of society that, if they knew [about the risk], would drink differently,” she said. Breast cancer in women came in third place for number of cases, with almost 100,000 cases (about 4% worldwide) attributable to alcohol use. “The breast cancer numbers are pretty high, just because breast cancer is so common,” Dr. LoConte explained. Cancers of the esophagus and liver accounted for more than 340,000 alcohol-attributable cancers diagnosed in 2020. The researchers solution focused therapy interventions estimated that, overall, about 17% of liver cancer cases and 32% of esophageal cancer cases diagnosed in 2020 were attributable to alcohol use. Dr. LoConte said that she has direct conversations with her patients about drinking and other behaviors that could affect their treatment.
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 foods that contain alcohol causality. „That’s similar in other high-income countries, and it’s probably even lower in other parts of the world.” The first mutation is a loss-of-function mutation in the gene for the enzyme aldehyde dehydrogenase 2 (ALDH2). These molecules can damage DNA, and the gene changes that result can lead to a cell turning cancerous. But much of the kind of work necessary to help people with substance abuse problems of any sort is beyond the realm of oncologists, he stressed.
- DHEAS is metabolised to oestrogen by aromatase, the activity of which is also increased in chronic alcohol consumers [40].
- Several other parameters (i.e., insulin sensitivity, leptin levels in the blood, and estrogen levels) were elevated in the alcohol-consuming mice.
- 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.
- An MR analysis by Ong and colleagues found no significant increase in breast cancer risk per genetically predicted drink per day (odds ratio 1.00 (95% CI 0.93–1.08)) [19].
- 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.
- In the study, many people being treated for cancer and longer-term cancer survivors reported regularly drinking alcohol—many moderately, but some also heavily and often.
“A lot of our surveys just estimate the total number of drinks per week and haven’t differentiated between the person who has one drink a day each week and someone who has 7 drinks just one day a week,” he said. “We are worried that 10 to 20 years down the road, we’re going to see a substantial increase in alcohol-related cancers,” Dr. Klein said. As it is highly reactive towards DNA, acetaldehyde may bind to DNA to form DNA adducts which alter its physical shape and potentially block DNA synthesis and repair [21]. These DNA adducts are particularly genotoxic as they can induce DNA point mutations, double-strand breaks, sister chromatid exchanges, and structural changes to chromosomes [21,22].
The overall percentage of all T cells, as well as of CD4+ T-, CD8+ T-, B-, and NK cells, in contrast, did not differ between cancer and control patients. However, this effect cannot be clearly attributed to alcohol because the patients also were heavy tobacco users. The study found that among healthy participants, those with high alcohol consumption or smoking had a pronounced decrease of antigen-specific antibody production in vitro. Cancer patients who were heavy drinkers, in contrast, did not show any antigen-specific antibody production in vitro.
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Sex hormone levels may be increased by alcohol through oxidative stress and through inhibition of the steroid degradation enzymes sulfotransferase and 2-hydroxylase [39]. Heavy use of alcohol has also been linked with increased circulating levels of oestrone and oestradiol as well as dehydroepiandrosterone sulphate (DHEAS) [39]. DHEAS is metabolised to oestrogen by aromatase, the activity of which is also increased in chronic alcohol consumers [40]. A large cohort study found DHEAS levels 25% higher among women consuming at least 20 g alcohol per day compared with non-drinkers [41].
Tumor metastasis is the ability of tumor cells to spread from their original site to other sites in the body and to re-establish growth, a new blood supply, and tumor colonies at the new location. (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). Several factors are involved in the invasion process, including the ability to activate enzymes called matrix metalloproteinases (MMP), which are important for the tumor cells to degrade basement membranes and underlying stroma. (2) The escaped cells reach the blood either directly by actively passing through endothelial cells that line the blood vessels or passively through the lymphatic system, which ultimately carries the tumor cells to the blood. (3) Once in the blood, the tumor cells exit into tissues at the secondary site from small capillaries by passing through endothelial cells and then invading the basement membrane of the ECM. Dormant cells also can proliferate at a future date and ultimately establish a new metastatic tumor.
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]. As with most questions related to a specific individual’s cancer treatment, it is best for patients to check with their health care team about whether it is safe to drink alcohol during or immediately following chemotherapy treatment.
More recent studies have evaluated the role of a protein famous fetal alcohol syndrome called macrophage migration inhibitory factor (MIF), which is an important regulator of the innate immune response. This factor has been studied in patients with lip or intra-oral squamous carcinoma as well as in patients who consumed alcohol regularly (Franca et al. 2013). The analyses found a significant relationship between the incidence of intra-oral cancer, alcohol use, and the number of MIF-positive cells in the stroma. Thus, MIF in the stroma of intra-oral tumors (i.e., tongue, floor of mouth, and alveolar ridge) was decreased in patients who consumed alcohol. The importance of these findings is unknown, although patients with tumors that did not express MIF had a worse prognosis than patients that did.
