Background: Alcohol is a risk factor for cancer of the oral cavity, pharynx, oesophagus, colorectum, liver, larynx and female breast, whereas its impact on other cancers remains controversial.

Methods: We investigated the effect of alcohol on 23 cancer types through a meta-analytic approach. We used dose-response meta-regression models and investigated potential sources of heterogeneity.

Results: A total of 572 studies, including 486 538 cancer cases, were identified. Relative risks (RRs) for heavy drinkers compared with nondrinkers and occasional drinkers were 5.13 for oral and pharyngeal cancer, 4.95 for oesophageal squamous cell carcinoma, 1.44 for colorectal, 2.65 for laryngeal and 1.61 for breast cancer; for those neoplasms there was a clear dose-risk relationship. Heavy drinkers also had a significantly higher risk of cancer of the stomach (RR 1.21), liver (2.07), gallbladder (2.64), pancreas (1.19) and lung (1.15). There was indication of a positive association between alcohol consumption and risk of melanoma and prostate cancer. Alcohol consumption and risk of Hodgkin's and Non-Hodgkin's lymphomas were inversely associated.

Conclusions: Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma.

Globally, ethanol — the principal form of alcohol in alcoholic beverages — is the most widely used psychoactive substance. In 2019, 44% of the global population 15 years of age or older had consumed alcohol in the previous year. The prevalence of alcohol consumption varies considerably according to geographic region, ranging from 4% in the World Health Organization (WHO) Eastern Mediterranean Region to at least 60% in the European, American, and Western Pacific Regions, and is higher among men than among women.

The International Agency for Research on Cancer (IARC) classified alcoholic beverages as carcinogenic to humans (Group 1) on the basis of sufficient evidence of causality for oral, pharyngeal, laryngeal, esophageal (squamous-cell), liver (hepatocellular), colorectal, and breast cancers (hereafter referred to as alcohol-related cancers). Ethanol in alcoholic beverages and acetaldehyde that is associated with consumption of alcoholic beverages are also classified as carcinogenic to humans (Group 1). Worldwide, in 2020, an estimated 741,300 new cancer cases (4.1% of all new cancer cases) were attributable to alcohol consumption (6.1% among men and 2.0% among women) (Table 1). Recently, the WHO stated that “no safe amount of alcohol consumption for cancers and health can be established.”

In 2010, the 63rd World Health Assembly endorsed the Global Strategy to Reduce the Harmful Use of Alcohol (resolution WHA63.13). Consistent with the objectives outlined in the Global Strategy is increasing knowledge about the potential benefits of alcohol reduction or cessation for decreasing alcohol-related cancer risks. From February through May 2023, the IARC Handbooks of Cancer Prevention Program convened a Working Group of 15 scientists (all of whom are coauthors of this article) from eight countries to review published studies and qualitatively evaluate the strength of epidemiologic evidence on the potential for alcohol reduction or cessation to reduce alcohol-related cancer risk and of mechanistic evidence on the potential effects of alcohol reduction or cessation to reduce alcohol-related carcinogenesis (no studies in experimental animals with a cancer outcome were available). Presented here is a summary and evaluation of the evidence.

Table 1:
Caption: Global Population Attributable Fractions and Number of New Cancer Cases Attributable to Alcohol Consumption in 2020, According to Cancer Site and Sex.*
Content:
Cancer Site,All,All,Men,Men,Women,Women
Unnamed: 0_level_1,Population Attributable Fraction,No. of New Cases†,Population Attributable Fraction,No. of New Cases†,Population Attributable Fraction,No. of New Cases†
Unnamed: 0_level_2,%,Unnamed: 2_level_2,%,Unnamed: 4_level_2,%,Unnamed: 6_level_2
All sites excluding nonmelanoma skin cancer (ICD-10 codes C00–C97 excluding C44),4.1,741300,6.1,568700,2.0,172600
Lip and oral cavity,20.2,74900,25.9,66700,7.3,8200
Pharynx,22.0,39400,25.3,37000,7.4,2500
Larynx,15.0,27600,16.6,26400,4.7,1200
Esophagus‡,31.6,189700,39.2,163100,14.3,26600
Colon,8.1,91500,13.0,76900,2.7,14600
Rectum,9.0,65100,13.0,57300,2.7,7800
Liver§,17.3,154700,22.7,141300,5.0,13400
Female breast,4.4,98300,—,—,4.4,98300

Alcohol consumption is the third major modifiable cancer risk factor after tobacco use and excess body weight.2 A standard drink of alcohol is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80-proof distilled spirits, which contain approximately 14 grams of ethanol, the primary form of alcohol found in alcoholic beverages.
Alcohol consumption is an established cause of at least 7 types of cancer. In 1987, an expert working group convened by the IARC first classified the consumption of alcoholic beverages as carcinogenic to humans.111 The evidence for causality was found to be sufficient for cancers of the upper aerodigestive tract (UADT) (ie, oral cavity, pharynx, larynx, squamous cell carcinoma of the esophagus) and liver. A second IARC expert working group convened in 2007 confirmed that alcohol consumption causes UADT and liver cancer, and they also found that there was sufficient evidence of causality for colorectal and female breast cancers. This second working group also found for the first time that “ethanol in alcoholic beverages” is carcinogenic to humans112; thus alcoholic beverages of all types increase risk. A 2009 IARC working group reaffirmed the previous conclusions, and added that both ethanol and acetaldehyde—the primary metabolite of ethanol ingestion associated with the consumption of alcoholic beverages—are a cause of cancers of the UADT.113 More recently, a 2018 WCRF/AICR Continuous Update Project report reaffirmed the strong evidence for those cancers (reported previously by other agencies) and also found that alcohol consumption probably increases the risk of stomach cancer.4 Importantly, alcohol consumption also interacts synergistically with tobacco use to increase the risk of cancers of the UADT considerably more than the risk associated with either drinking alcohol or tobacco use alone.112 Of particular relevance for cancer prevention guidelines is evidence showing that consumption of any amount of alcohol increases risk of some types of cancer, most notably breast cancer.4

Background: Alcohol use is causally linked to multiple cancers. We present global, regional, and national estimates of alcohol-attributable cancer burden in 2020 to inform alcohol policy and cancer control across different settings globally.

Methods: In this population-based study, population attributable fractions (PAFs) calculated using a theoretical minimum-risk exposure of lifetime abstention and 2010 alcohol consumption estimates from the Global Information System on Alcohol and Health (assuming a 10-year latency period between alcohol consumption and cancer diagnosis), combined with corresponding relative risk estimates from systematic literature reviews as part of the WCRF Continuous Update Project, were applied to cancer incidence data from GLOBOCAN 2020 to estimate new cancer cases attributable to alcohol. We also calculated the contribution of moderate (<20 g per day), risky (20-60 g per day), and heavy (>60 g per day) drinking to the total alcohol-attributable cancer burden, as well as the contribution by 10 g per day increment (up to a maximum of 150 g). 95% uncertainty intervals (UIs) were estimated using a Monte Carlo-like approach.

Findings: Globally, an estimated 741 300 (95% UI 558 500-951 200), or 4·1% (3·1-5·3), of all new cases of cancer in 2020 were attributable to alcohol consumption. Males accounted for 568 700 (76·7%; 95% UI 422 500-731 100) of total alcohol-attributable cancer cases, and cancers of the oesophagus (189 700 cases [110 900-274 600]), liver (154 700 cases [43 700-281 500]), and breast (98 300 cases [68 200-130 500]) contributed the most cases. PAFs were lowest in northern Africa (0·3% [95% UI 0·1-3·3]) and western Asia (0·7% [0·5-1·2]), and highest in eastern Asia (5·7% [3·6-7·9]) and central and eastern Europe (5·6% [4·6-6·6]). The largest burden of alcohol-attributable cancers was represented by heavy drinking (346 400 [46·7%; 95% UI 227 900-489 400] cases) and risky drinking (291 800 [39·4%; 227 700-333 100] cases), whereas moderate drinking contributed 103 100 (13·9%; 82 600-207 200) cases, and drinking up to 10 g per day contributed 41 300 (35 400-145 800) cases.

Interpretation: Our findings highlight the need for effective policy and interventions to increase awareness of cancer risks associated with alcohol use and decrease overall alcohol consumption to prevent the burden of alcohol-attributable cancers.

Funding: None.

Background: Alcohol consumption has been associated with increased risks of certain site-specific cancers and decreased risks of some other cancers. There is, however, little reliable evidence as to whether the alcohol-associated risks for specific cancers are modified by smoking, body mass index (BMI) and menopausal hormone therapy (MHT) use.

Methods: In the prospective UK Million Women Study, 1,233,177 postmenopausal women without prior cancer, mean age 56 (SD 5) years, reported their alcohol consumption in median year 1998 (IQR 1998-1999), and were followed by record-linkage for incident cancer. 438,056 women who drank no alcohol or < 1 drink/week were excluded. Cox regression yielded adjusted relative risks (RRs) and 95% confidence intervals (CIs) for 21 cancers by alcohol amount; statistical significance of interactions with smoking, BMI and MHT use was assessed after allowing for multiple testing.

Results: In 795,121 participants, mean consumption was 6.7 (SD 6.4) alcoholic drinks/week. During 17 (SD 5) years of follow-up, 140,203 incident cancers were recorded. There was strong evidence for a substantial association between alcohol intake and risk of upper aero-digestive cancers (oesophageal squamous cell carcinoma, oral cavity, pharynx and larynx; RR per 1 drink/day = 1.38 [95% CI 1.31-1.46]). There was also strong evidence for more moderate positive associations with breast, colorectal and pancreatic cancer (RRs per 1 drink/day = 1.12 [1.10-1.14], 1.10 [1.07-1.13], 1.08 [1.02-1.13] respectively), and moderate negative associations with thyroid cancer, non-Hodgkin's lymphoma, renal cell carcinoma and multiple myeloma (RRs per 1 drink/day = 0.79 [0.70-0.89], 0.91 [0.86-0.95], 0.88 [0.83-0.94], 0.90 [0.84-0.97] respectively). Significant interactions between alcohol and smoking were seen for upper aero-digestive cancers (RRs per 1 drink/day = 1.66 [1.54-1.79], 1.23 [1.11-1.36], 1.12 [1.01-1.25] in current, past, and never smokers respectively). BMI and MHT did not significantly modify any alcohol-associated risks.

Conclusions: These findings provide robust evidence that greater alcohol intake, even within relatively moderate ranges, increases the risk of cancers of the aerodigestive tract, breast, colorectal and pancreatic cancer, and probably decreases the risk of thyroid cancer, non-Hodgkin's lymphoma, renal cell carcinoma and multiple myeloma. Associations of alcohol intake with cancer risk were not modified by MHT use, adiposity or smoking, except in the case of upper aero-digestive cancers, where the alcohol-associated risk was largely confined to smokers.

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.

Background: Although overall alcohol consumption is known to increase the risk of a number of cancers internationally, evidence for Australia and evidence regarding the pattern of drinking and cancer risk is limited.

Methods: Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for cancer risk in relation to overall alcohol consumption (drinks/week) and pattern of drinking were calculated using Cox proportional hazard regressions for 226,162 participants aged ≥45 years (2006-2009) in the 45 and Up Study, an Australian prospective cohort study. Incident primary cancer cases were ascertained by linkage to the New South Wales Cancer Registry to 2013 by the Centre for Health Record Linkage.

Results: Over a median of 5.4 years, 17,332 cancers were diagnosed. Increasing levels of alcohol intake were associated with increased risk of cancers of the upper aerodigestive tract (1.19; 1.10-1.29), mouth and pharynx (1.18; 1.08-1.29), oesophagus (1.22; 1.04-1.43), colorectum (1.09; 1.04-1.15), colon (1.13; 1.06-1.20), liver (1.22; 1.04-1.44) and breast (1.11; 1.02-1.21). Breast cancer risk was marginally associated with drinking pattern, with higher risk when intake was concentrated on 1-3 days/week compared to the same amount spread over 4-7 days (P = 0.049).

Conclusions: Alcohol consumption confers a significant risk of cancer, and drinking pattern may be independently related to breast cancer risk.

Aims: Cancers of female breast, upper aero-digestive tract (UADT) (oral cavity, pharynx, larynx, oesophagus) and colorectum are causally related to alcohol consumption. Although alcohol consumption is likely to vary during life, the few studies that have explicitly measured lifetime consumption or intake over time have not been summarised. We therefore conducted a systematic review and meta-analysis.

Methods: Studies were identified by searching the Medline, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and Scopus databases through January 2015 using broad search criteria. Studies reporting relative risks (RR) for quantitatively defined categories of alcohol consumption over time for breast, UADT or colorectal cancer were eligible. A two-stage random-effects meta-analysis was used to estimate a dose-response relationship between alcohol intake and each cancer site. RRs were also calculated for the highest relative to the lowest intake category.

Results: Sixteen articles for breast, 16 for UADT and 7 for colorectal cancer met the eligibility criteria. We observed a weak non-linear dose-response relationship for breast cancer and positive linear dose-response relationships for UADT and colorectal cancer. The pooled RRs were 1.28 (95% confidence interval,

Ci: 1.07, 1.52) for breast, 2.83 (95%

Ci: 1.73, 4.62) for UADT, 4.84 (95%

Ci: 2.51, 9.32) for oral cavity and pharynx, 2.25 (95%

Ci: 1.49, 3.42) for larynx, 6.71 (95%

Ci: 4.21, 10.70) for oesophageal and 1.49 (95%

Ci: 1.27, 1.74) for colorectal cancer.

Conclusion: Our findings confirm dose-dependent associations between long-term alcohol intake and breast, UADT and colorectal cancer.

Background: There is convincing evidence that alcohol consumption increases the risk of cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx. Most of the data derive from studies that focused on the effect of moderate/high alcohol intakes, while little is known about light alcohol drinking (up to 1 drink/day).

Patients And Methods: We evaluated the association between light drinking and cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx, through a meta-analytic approach. We searched epidemiological studies using PubMed, ISI Web of Science and EMBASE, published before December 2010.

Results: We included 222 articles comprising ∼92 000 light drinkers and 60 000 non-drinkers with cancer. Light drinking was associated with the risk of oropharyngeal cancer [relative risk, RR = 1.17; 95% confidence interval (CI) 1.06-1.29], esophageal squamous cell carcinoma (SCC) (RR = 1.30; 95% CI 1.09-1.56) and female breast cancer (RR = 1.05; 95% CI 1.02-1.08). We estimated that ∼5000 deaths from oropharyngeal cancer, 24 000 from esophageal SCC and 5000 from breast cancer were attributable to light drinking in 2004 worldwide. No association was found for colorectum, liver and larynx tumors.

Conclusions: Light drinking increases the risk of cancer of oral cavity and pharynx, esophagus and female breast.

Background And Aims: There is increasing research evidence about the causal role of alcohol in cancer, accompanied by unclear and conflicting messages in the media. This paper aimed to clarify the strength of the evidence for alcohol as a cause of cancer, and the meaning of cause in this context.

Methods: Recent epidemiological and biological research on alcohol and cancer was reviewed and summarized, drawing upon published meta-analyses identified from the Medline database and the archives of the International Agency for Research on Cancer. More recent epidemiological studies not included in these publications were also reviewed. A brief description of the nature of causal inference in epidemiology was used to frame discussion of the strength of the evidence that alcohol causes cancer, and contrast this with the case for a protective association of alcohol with cardiovascular disease.

Results: The usual epidemiological understanding of a cause is a factor that increases the incidence of a condition in the population. In the context of a body of epidemiological evidence of an association of alcohol consumption with a disease, the inference that it is a causal association requires alternative explanations of the observed finding to be judged unlikely. Even without complete knowledge of biological mechanisms, the epidemiological evidence can support the judgement that alcohol causes cancer of the oropharynx, larynx, oesophagus, liver, colon, rectum and breast. The measured associations exhibit gradients of effect that are biologically plausible, and there is some evidence of reversibility of risk in laryngeal, pharyngeal and liver cancers when consumption ceases. The limitations of cohort studies mean that the true effects may be somewhat weaker or stronger than estimated currently, but are unlikely to be qualitatively different. The same, or similar, epidemiological studies also commonly report protection from cardiovascular disease associated with drinking but a high level of scepticism regarding these findings is now warranted.

Conclusions: There is strong evidence that alcohol causes cancer at seven sites in the body and probably others. Current estimates suggest that alcohol-attributable cancers at these sites make up 5.8% of all cancer deaths world-wide. Confirmation of specific biological mechanisms by which alcohol increases the incidence of each type of cancer is not required to infer that alcohol is a cause.

This review focuses on selected aspects of the relation between alcohol consumption and cancer risk. Heavy alcohol consumption (i.e., ≥4 drinks/day) is significantly associated with an increased risk of about 5-fold for oral and pharyngeal cancer and esophageal squamous cell carcinoma, 2.5-fold for laryngeal cancer, 50% for colorectal and breast cancers, and 30% for pancreatic cancer. These estimates are based on a large number of epidemiological studies and are generally consistent across strata of several covariates. The evidence suggests that at low doses of alcohol consumption (i.e., ≤1 drink/day) the risk is also increased by about 20% for oral and pharyngeal cancer and 30% for esophageal squamous cell carcinoma. Thus, for these sites there is little evidence of a threshold effect. While consumption of fewer than 3 alcoholic drinks/wk is not associated with an increased risk of breast cancer, an intake of 3 to 6 drinks/wk might already yield a (small) increase in risk. On the other hand, intakes up to 1 drink/day are not associated to the risk of laryngeal, colorectal, and pancreatic cancer. The positive association between alcohol consumption and the risk of head and neck cancers is independent from tobacco exposure.

A causal association has been established between alcohol consumption and cancers of the oral cavity, pharynx, larynx, oesophagus, liver, colon, rectum, and, in women, breast; an association is suspected for cancers of the pancreas and lung. Evidence suggests that the effect of alcohol is modulated by polymorphisms in genes encoding enzymes for ethanol metabolism (eg, alcohol dehydrogenases, aldehyde dehydrogenases, and cytochrome P450 2E1), folate metabolism, and DNA repair. The mechanisms by which alcohol consumption exerts its carcinogenic effect have not been defined fully, although plausible events include: a genotoxic effect of acetaldehyde, the main metabolite of ethanol; increased oestrogen concentration, which is important for breast carcinogenesis; a role as solvent for tobacco carcinogens; production of reactive oxygen species and nitrogen species; and changes in folate metabolism. Alcohol consumption is increasing in many countries and is an important cause of cancer worldwide.