April 2018 Issue

Alcohol Consumption and Cancer Risk — The Other Side of a Health Halo
By Karen Collins, MS, RDN, CDN, FAND
Today's Dietitian
Vol. 20, No. 4, P. 34

Many people give alcohol a "health halo" because of its association with lower heart disease risk—although even this association pertains to amounts of alcohol only within the limits of moderation.1 But the side of alcohol that's often overlooked is its role in raising cancer risk. In fact, surveys suggest that 60% to 70% of Americans are unaware of the alcohol-cancer link.2,3

This article will provide dietitians with an update and big-picture view of the research about alcohol and cancer risk and help identify talking points for discussions with clients and patients.

Research Overview
Analysis conducted as part of the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Continuous Update Project includes a systematic review of all available research from around the world graded for quality. Reports based on this analysis identify evidence as convincing (the strongest grade of evidence), linking alcohol with increased risk of cancers of the breast (postmenopausal), colorectum, esophagus (squamous cell), liver, mouth, pharynx, and larynx. The analysis also cites probable increased risk of stomach and premenopausal breast cancers.

Considering overall cancer, which may include some forms that are less influenced by alcohol, cancer risk in men who consume less than two alcoholic drinks per day and women who consume less than one drink per day is 6% lower than in people with higher alcohol consumption, according to analysis conducted for the European Code Against Cancer project.4 Any reduction in alcohol consumption has a beneficial effect on reducing cancer risk.4

The magnitude of alcohol's association with cancer differs with type of cancer and the level of alcohol consumption. Understanding the dose-response relationship is an important underpinning for communication about risk with patients. Individual studies vary in how they classify levels of alcohol consumption. Light drinking in many studies refers to 12.5 g of ethanol (pure alcohol) per day or less.5 In the United States, this would translate to no more than about one standard alcoholic drink per day. In some studies, however, up to 25 g of ethanol per day may be grouped with "light" drinking.4 Most studies classify moderate drinking as between 12.5 and 50 g of ethanol per day, and heavy drinking as greater than 50 g per day (more than about four drinks per day).4,5

Alcohol-related risk should be of special concern to women, since increased breast cancer risk starts at consumption of fewer than one drink per day.6 Just 10 g of ethanol consumed daily raises risk of premenopausal breast cancer 5%, and risk of postmenopausal breast cancer 9%, compared with women who don't drink alcohol.7

Likewise, there's been no "safe" threshold identified for upper digestive tract cancers that involve tissues that come into direct contact with alcohol consumed. Risk of squamous cell esophageal cancer increases 25% per 10 g daily ethanol.8 For oropharyngeal cancers, analyses that include both cohort and case-control studies (which may therefore be somewhat less reliable than the WCRF/AICR Continuous Update Project analyses) identify a 13% to 23% increase in risk with one standard drink per day, and a 500% to 600% increase in risk for heavy drinkers consuming four or more drinks per day.4,5

When alcohol intake exceeds two standard drinks per day, it also adds a statistically significant increase in risk of cancers of the larynx, colorectum, and liver. Risk of laryngeal cancer among moderate drinkers (between 12.6 and 50 g per day) is 44% higher than nondrinkers, and risk is more than double among heavy drinkers.4,5 Risk of liver cancer increases 4% for each 10 g of alcohol consumed daily, although this doesn't become significant until intake exceeds 45 g per day (about four standard US drinks).9 Colorectal cancer risk increases 7% for each 10 g of alcohol consumed daily, but this becomes statistically significant at 30 g or more.10

Research Evaluation Challenges
This view of alcohol as a health risk may be surprising to many people, since it's commonly associated with lower heart disease risk. Alcohol in moderation can reduce cardiovascular risk by increasing HDL cholesterol and reducing insulin resistance and fibrinogen levels.1 However, alcohol beyond moderation can raise blood pressure11,12 and serum triglycerides,13 and lead to cardiomyopathy.1 Alcohol also can contribute to excessive calorie consumption, promoting unhealthy weight gain.1,14 This can lead to chronic inflammation and insulin resistance, which raise risk of both CVD and cancer.

One analysis shows lower coronary heart disease incidence (but not stroke incidence) with alcohol in the range equivalent to one drink per week to one drink per day compared with intake less than that; but intake beyond that isn't associated with any additional risk reduction.15 For cardiovascular mortality and all-cause mortality, alcohol consumption exhibits a "J-shaped curve."1,15 Lowest risk is observed between one drink per week and one drink per day (average daily intake 2.5 to 14.9 g of ethanol), and risk begins to increase above that level.1

An effect known as "abstainer bias" poses challenges for interpreting these observational studies. Some people in these studies with little or no alcohol consumption include people who already have health problems that led them to avoid alcohol.1 This can make current low-volume drinkers appear healthier than nondrinkers, when the latter includes former and occasional drinkers. Best practice is for research analysis to group "never drinkers" separately from "former drinkers," but many studies comparing health outcomes in relationship to different levels of alcohol intake omit this step.

For example, a meta-analysis of 87 studies shows a J-shaped curve for alcohol consumption and all-cause mortality. People who consumed 1.3 to 24.9 g of ethanol per day (low-volume drinkers) demonstrated a 14% lower risk than nondrinkers.16 However, after adjustment for abstainer bias and quality-related study characteristics, these low-volume drinkers had no significant difference in mortality risk than nondrinkers. In another analysis, however, although the reduction in cardiovascular mortality was smaller when active drinkers were compared with lifetime abstainers instead of all nondrinkers, some reduction was still apparent.15

Problems inherent in observational studies lead to some questions about interpreting alcohol's association with cancer risk, too. "Recall bias" is a concern in all studies of self-reported dietary intake, and many researchers note that people tend to underreport alcohol intake. This could mean that cancer risk associated with low levels of alcohol consumption is overstated, essentially representing risk of higher intake.17

Why Would Alcohol Raise Cancer Risk?
Regardless of the challenges observational studies pose, an important message point is that WCRF/AICR recommendations for cancer prevention are issued only when studies from laboratory and human randomized controlled trials identify mechanisms that support findings from human population studies. Several mechanisms may account for alcohol's role in cancer development.

• Increased circulating estrogen seems to be an important reason for alcohol's link to breast cancer, and explains why risk of estrogen receptor-positive breast cancer (the most common form) particularly rises with alcohol consumption.7,18,19 Women often ask about whether certain foods may be "estrogenic," yet completely overlook this effect of alcohol.

• DNA damage can occur from the free radicals formed as alcohol, a recognized carcinogen, is metabolized, forming acetaldehyde, another recognized carcinogen. Alcohol also may act as a solvent, increasing other carcinogens' ability to damage cells.4,6-10,18

• Chronic tissue inflammation can result from drinking alcohol at levels high enough to produce oxidative stress, contrary to low levels of inflammation biomarkers associated with low-volume alcohol consumption in some observational studies.6 For example, tissue damage in the liver from high levels of alcohol that lead to cirrhosis is a cause of the hepatocellular form of liver cancer.6,9

• Genetics. It's possible that genetic predisposition may increase cancer risk from alcohol. People with specific variations in the gene encoding the enzyme responsible for breaking down the acetaldehyde generated from alcohol accumulate higher levels of acetaldehyde, amplifying its carcinogenic potential. This could lead to greater susceptibility to alcohol-induced cancer for these individuals, but more research is needed.6,18 For smokers, the alcohol-related risk of cancers of the mouth, larynx, and esophagus increases synergistically.14 For breast cancer, some studies suggest there's a window of greatest vulnerability when alcohol consumed before a first pregnancy may increase cancer risk.20,21 However, other research concludes that total lifetime alcohol exposure is the most important way of expressing risk.4

Talking Points About Alcohol and Health
• Moderate drinking may mean less alcohol than people think. For women, moderation is defined as up to one standard alcoholic drink per day, and for men, up to two.22 That standard drink (defined as one providing 14 g of ethanol) is equivalent to 5 oz of wine, 12 oz of beer, or a 1.5-oz shot of 80-proof liquor.

When working with individual clients or patients, it's important to ask about the particular alcoholic beverages they choose when discussing moderate alcohol consumption. For example, the 12-oz serving of beer refers to traditional beer that's 5% alcohol. Craft beers are becoming increasingly popular, however, and often contain 6.5% or 7% alcohol, and the number of beers over 8% alcohol is growing as well. For these beers, one serving isn't 12 oz, but 9 oz or less. Likewise, for people who choose 100-proof liquor, one serving equivalent isn't 1.5 oz, but 1.2 oz.

• Common serving sizes can be deceiving. As glass sizes have increased, many people are unaware that what seems like one drink is substantially more.6,17 For example, a standard all-purpose wineglass used to be about 8 oz, which fit a standard 5-oz serving of wine, since wineglasses aren't meant to be poured full in order to provide enough room to swirl the wine in the glass and hold the aroma. However, 12- to 16-oz wineglasses have now become standard in many restaurants and homes. Especially if people fill these glasses beyond the traditional one-third to one-half point, "one glass" of wine can be two or more standard servings of alcohol. Likewise, people who drink cocktails that include more than one shot of alcohol may consider it "one drink," even though alcohol content is at least double that. Beers poured on tap often are served in pint glasses, which may make 16 oz, rather than 12 oz, seem like "one beer."

• Binge drinking isn't moderate drinking, regardless of whether it averages out over the course of a week to the same total amount of alcohol defined as moderate drinking.1,14 The 2015–2020 Dietary Guidelines for Americans specifically note that the definition of moderate drinking isn't intended as an average over several days, but rather the amount consumed on any single day.22

Binge drinking raises risk of heart disease.23 Studies on binge drinking and breast cancer risk are still limited, but available evidence shows risk increases from 33% for monthly binge drinking to 55% for weekly binge drinking.4 Binge drinking is defined as consumption of four or more drinks during a single occasion for women, or five or more drinks during a single occasion for men.6,24,25

• Limits for women and older adults are lower. The same amount of alcohol poses more risk for women because differences in alcohol metabolizing enzymes and total body water make alcohol more concentrated in the blood and is more slowly eliminated than in men.17,26 The same concerns seem to apply to older adults of both genders.27

• Wine is not "safe" alcohol. Some sources talk about wine as a more healthful choice of alcohol and suggest that the phytochemical called reservatrol in red wine may be protective. However, the association between alcohol drinking and cancer risk is consistent, regardless of whether it's beer, wine, or distilled liquor. And among wine drinkers, risk doesn't vary by choice of red, white, or a mixture.6,18 Although scores for higher adherence to a Mediterranean diet link to lower CVD risk and a modestly lower cancer risk, moderate wine intake accounts for only one point out of nine in those scores, and intake beyond 15 g per day doesn't add any points to the Mediterranean score.28 Moreover, researchers noted that wine as traditionally consumed in the Mediterranean diet was in moderate amounts and consumed at meals—not in a binge-drinking context— which slows alcohol absorption and results in lower peak levels for the body to handle.29,30

• Alcohol is a concern for cancer survivors, too. Although alcohol is a well-established risk factor for the development of certain cancers, it's unclear how postdiagnosis alcohol use affects cancer treatment and long-term survival.31 In one systematic review and meta-analysis, when pre- and postdiagnosis alcohol consumption were considered together, people with highest intake had 17% increased risk of recurrence and 8% increased all-cause mortality compared with people with lowest intake.32 However, when postdiagnosis intake alone was considered, highest intake was associated with 31% increased risk of recurrence, but there was no association with overall mortality.32

During cancer treatment, some patients or their families may ask about alcohol to stimulate appetite and boost calorie intake. However, limited data from controlled trials don't support a benefit for appetite or weight stability in advanced cancer.6 A significant number of people with upper aerodigestive tract cancer reportedly continue to drink alcohol after diagnosis.6 Among these patients, some studies link moderate (12.6 to 49.9 g per day) and heavy (50 g per day or more) alcohol consumption during and after radiation treatment with increased risk of osteoradionecrosis of the jaw, second primary tumors, and cancer mortality.6

Despite alcohol's clear association with breast cancer risk, the WCRF/AICR review found data too limited to make any conclusions about alcohol use in breast cancer survivors.31 Whether considering intake prediagnosis, within 12 months of diagnosis, or 12 months or more after diagnosis, and whether based on high vs low intake or one drink per day, analysis didn't show any significant association with breast cancer mortality, all-cause mortality, or second primary cancer.

Common Ground Bottom Line
Alcohol poses greatest cancer risk with long-term heavy consumption. But there's some risk with intake defined as moderate, and some cancer risk even at low levels of consumption.4,6-10 Just as wearing sunscreen can reduce skin cancer risk, limiting alcohol is one of several steps people can take to reduce overall cancer risk.33

Whether focused on heart health or lower cancer risk, recommendations agree that for those who choose to drink alcohol, it's best for women to drink no more than one standard drink per day, and men to drink no more than two standard drinks per day.

— Karen Collins, MS, RDN, CDN, FAND, is a nutrition consultant specializing in cancer prevention and cardiometabolic health, and a nutrition advisor to the American Institute for Cancer Research.

References
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