A new advisory by the US Surgeon General highlights a topic that – as the document itself notes – has been flying mostly under the public’s radar: the relationship between alcohol consumption and cancer. While most people are aware of smoking and obesity being risk factors for cancer, apparently, less than half of Americans know that a growing body of evidence links alcohol to this deadly disease.
A major preventable risk factor
The advisory, based on the current state of research, calls alcohol “a leading preventable cause of cancer in the United States, contributing to nearly 100,000 cancer cases and about 20,000 cancer deaths each year.” Alcohol consumption is linked to at least seven cancer types: breast, colorectum, esophagus, liver, mouth, throat, and larynx.
“It appears that alcohol is most closely linked to the cancers of all levels of the digestive system, which is expected, as alcohol causes DNA damage, creating dangerous mutations and causing a malignant transformation in some cells,” explained Anna Barkovskaya, PhD, of Lifespan Research Institute. “This is most likely to happen in tissues that it directly comes into contact with.”
There is one notable outlier, however: breast cancer. The advisory speculates that alcohol could elevate the risk of breast cancer by affecting hormonal levels. “It is unclear and unproven, however, as the advisory itself mentions, that this takes place,” Barkovskaya explained. “It is also unclear and unspecified why this does not occur in men and why there does not appear to be a link with prostate cancer.”
The numbers
According to the document, alcohol consumption is the third leading preventable cause of cancer in the US, after tobacco and obesity. “In absolute numbers, in 2019,” it says, “an estimated 96,730 cancer cases were related to alcohol consumption, including 42,400 in men and 54,330 in women. This translates to nearly 1 million preventable cancer cases over ten years in the U.S.”
In general, the higher the alcohol consumption, the greater the risk of cancer. However, alarmingly, at least with breast, mouth, and throat cancers, the risk increase starts even at low levels of consumption, even at less than one drink per day on average. 83% of alcohol-related cancer deaths are associated with levels of alcohol consumption above the recommended limit of two drinks daily for men and one drink daily for women. Still, the remaining 17% occur below this threshold.
In American women, the largest burden of alcohol-related cancer is for breast cancer: estimated 44,180 cases in 2019. For men, the leading alcohol-related cancers are liver and colorectal.
“Breast cancer is the most common cancer type in women,” Barkovskaya mentioned. “However, it is very diverse, and the different brands of this disease are caused by distinct molecular dysfunctions. It is therefore unclear exactly how and if alcohol directly promotes breast cancer, or if this effect reflects a broader alcohol-related cancer probability increase.”
Discussing the actual increases in risk, the advisory cites a study that reported that in women, the absolute lifetime risk of developing any alcohol-related cancer increases from 16.5% to 19.0% for those who consume one drink daily on average and to 21.8% for those who consume two drinks daily on average, compared to those consuming less than one drink per week. In other words, even heavy drinking increases a woman’s chances to get cancer by only about 5 percentage points. For men, those figures are 10%, 11.4%, and 13.1%, respectively.
The mechanisms
The advisory offers some thoughts on possible mechanisms that link alcohol to cancer, while admitting those are still under investigation. “Multiple studies,” it says, “have shown that giving rats and mice drinking water with ethanol or its primary metabolic breakdown product, acetaldehyde, results in increased tumor numbers at multiple places in the body. At high levels such as those that occur with consumption of alcohol, acetaldehyde is highly toxic and cancer-causing.”
Acetaldehyde causes cancer by binding to DNA and damaging it, which can trigger oncogenic mutations. On top of that, alcohol generates reactive oxygen species, which promote inflammation and can also damage DNA, proteins, and lipids through oxidation.
The third possible mechanism involves alcohol altering hormone levels, including estrogen, which might be relevant for breast cancer. Finally, the report says, carcinogens from other sources, such as particles of tobacco smoke, can dissolve in alcohol, which would increase their absorption.
“The best-established evidence is on the first two pathways of acetaldehyde and inflammation,” the document concludes. “Hormonal regulation and alcohol as a solvent are widely agreed upon to be important pathways for carcinogenesis but are not yet fully understood.”
Isn’t moderate drinking good for you?
Longevity physician David Barzilai, MD, PhD, fittingly calls the report “quite sobering” and adds that it “challenges the presumed protective role of moderate alcohol consumption and emphasizes the need for improved methodologies to address this critical public health issue.”
Indeed, until fairly recently, most research showed a U-shaped (or J-shaped) association between alcohol and mortality, meaning that the lowest risk corresponds to moderate levels of consumption. Newest findings, however, suggest a more linear correlation.
One possible cause of misinterpreting the real nature of the relationship is reverse causation, when people give up drinking after having developed health problems. This artificially elevates average risk levels for teetotalers and lowers them for drinkers. Most of the data in this field comes from population studies, which are notoriously noisy and can only establish correlation but not causation. Essentially, the jury is still out.
While some researchers hold that we should completely give up alcohol, Barzilai strikes a moderate tone: “While a well-validated lower boundary of the dose-response curve between alcohol intake and cancer risk remains unclear (and there may be no minimum threshold effect), the absolute risk of cancer is especially low for individuals consuming two or fewer alcoholic beverages per week. For those who enjoy the social aspects of alcohol, it seems reasonable to follow previous guidelines.”
The recommendations
Unsurprisingly, quitting or reducing drinking helps. According to a recent evidence review cited in the advisory, alcohol cessation or reduction decreases the risk of mouth cancer and esophageal cancer. “More research is needed to determine if this risk decreases for other cancer sites and whether it decreases to the level observed in people who never consume alcohol,” the authors say.
The numbers featured in the advisory are population averages and don’t tell a lot about personal risk levels, which can be affected by people’s genetic makeup. Thankfully, today, anyone can have their genome sequenced to assess their personal vulnerability. For instance, the document says, “many individuals of East Asian descent have a genetic variant that results in an alcohol flushing response and reduces their ability to metabolize acetaldehyde, which produces much higher risks for certain alcohol-related cancers.”
The advisory also calls for increasing public awareness of alcohol consumption as a risk factor for cancer. To do so, the authors recommend updating the existing Surgeon General’s health warning label on alcoholic beverages with a specific warning about alcohol increasing cancer risk. However, this is a Congressional prerogative that requires political involvement to set into motion.
“It would be interesting,” Barkovskaya mused, “to explore the link between cancer and alcohol from the viewpoint of aging. Much of the damage caused by alcohol is exactly the kind that is known to promote aging. Cancer, broadly, is also a disease of aging. This begs a question if alcohol consumption at different points in life has different effects on aging, and by extension – cancer and the resulting lifespan.”
