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The ALDH2 Gene: How Much Does Drinking Alcohol Increase Cancer Risk?

Alcohol and cancer risk

You may be aware of the link between alcohol and cancer, but do you know how alcohol causes cancer and how much your risk of developing cancer increases if you consume alcohol regularly?

These questions have been answered, and in a nutshell, evidence is accumulating showing that a definite dose-dependent effect exists; that is, the more you drink, the higher your risk is. Also, research has found that alcohol causes site-specific cancers, meaning that certain organs are more at risk of becoming cancerous as opposed to others when we drink alcohol. In particular, there are genes that predispose some of us to a much greater risk of colon cancer when we drink alcohol.

According to the National Institute on Alcohol Abuse and Alcoholism, a standard alcoholic drink in the USA contains 0.6 ounces of pure alcohol. Generally, this amount of pure alcohol is found in:

  • 12 ounces of beer
  • 8–9 ounces of malt liquor
  • 5 ounces of wine
  • 1.5 ounces, or 1 “shot,” of 80-proof distilled spirits (liquor)

As you can see, the amount of pure alcohol you can consume on a night out can rise pretty quickly, but what effect does this have? Let’s take a closer look at the link between alcohol consumption and cancer risk.

What are the risks of drinking alcohol?

The World Health Organization (WHO) estimates that alcohol is responsible for approximately 2.5 million deaths each year and 4.5% of the global burden of disease and injury 1.

Alcohol consumption is a major behavioral risk factor for cancer in particular. The notion of a possible link between alcohol consumption and cancer was explored as early as the 1900s 2 and has been confirmed by multiple studies since.

So, what are the risks?

Heavy alcohol consumption, defined as consuming 4 or more drinks a day has been associated with 3:

  • A 5-fold increase in risk for oral, pharyngeal cancer, and esophageal cancer
  • A 2.5-fold increase in risk for laryngeal cancer
  • 50% increase in risk for colorectal and breast cancers
  • 30% increase in risk for pancreatic cancer.

Research has found that even low levels of alcohol consumption (1 drinks per day) increase your risk of cancer development 3:

  • 20% increase for oral and pharyngeal cancer
  • 30% increase for esophageal cancer.

You’ll notice that besides breast cancer, all of these cancers are linked to the digestive tract and this is significant because over time, in someone who regularly consumes alcohol, constant exposure of these sites with alcohol can be detrimental. This chronic exposure has been linked to a change in the activity of the cells, which may lead to them becoming cancerous.

How does this happen?

After the confirmation that alcohol did indeed increase the risk of cancer, researchers set out to confirm why and how this happens.

The first mechanism they came across was that when alcohol is metabolized, it is broken down into acetaldehyde, which is a toxic chemical and human carcinogen (cancer-causing) 4. Acetaldehyde can damage both DNA (the genetic material in the cells) and proteins. It’s also interesting to note that SNPs or variations in the aldehyde dehydrogenase 2 (ALDH2) gene (codes for the enzyme that breaks down acetaldehyde) has been linked to cancers of the upper digestive tract.

The second mechanism that was found was that alcohol consumption generated reactive oxygen species in the cells with which it came into contact. The resulting oxidative stress causes damage to DNA, proteins, and lipids (fats) in the body which cultivates a tumor-forming environment 5.

The effects mentioned above are caused by the ethanol molecule itself and how our bodies react to it, but did you know that many alcoholic drinks contain a variety of carcinogenic (cancer-causing) contaminants? True story.

These contaminants are introduced during the fermentation and production process and include compounds such as phenols, nitrosamines, asbestos fibers, and hydrocarbons.

The link between alcohol consumption and colon cancer

There is a convincing link between the development of colorectal cancer (CRC) and the Western diet and lifestyle, so it’s no surprise then that alcohol has come up as one of the main risk factors for the development of this disease.

As I mentioned previously, it is estimated that alcohol increases the chance of CRC by 50%. CRC development has shown a dose-dependent effect with alcohol consumption, meaning that light to moderate drinking has little effect, but heavy drinking causes a remarkable increase in CRC risk 5.

Genetic variations in alcohol metabolizing enzymes can increase CRC risk

The effect of alcohol consumption can vary according to differences in genes that encode enzymes involved in ethanol metabolism. Research has found that ALDH2 polymorphisms (genetic code variations) have significant clinical implications6.

A striking genetic polymorphism that dramatically reduces ALDH2 enzyme activity and affects alcohol metabolism is the dysfunctional ALDH2 A allele. In carriers of the AA (homozygous,2 copies) and ALDH2 AG (heterozygous,1 copy) genotypes, the ALDH enzyme activity is nearly 0% and 17–38% of the normal activity, respectively7. This is a huge reduction in enzyme activity and leads to the accumulation of acetaldehyde in the circulation even after a moderate amount of alcohol.

The effects of the accumulation of acetaldehyde manifest as “Alcohol Flushing Syndrome” and is characterized by facial redness, nausea, tachycardia, palpitations, and unpleasant feelings when alcohol is consumed by these individuals. This ALDH2 deficiency is surprisingly common and is carried by approximately 8% of the world’s population.

Studies linking the presence of the ALDH2 deficiency to CRC and other cancers are conflicting because individuals with this deficiency often tend to avoid alcohol completely, due to the unpleasant effects that it causes. However, in those that are heavy drinkers and possess this deficiency, an increase in CRC is observed 8.

Can you reduce your risk?

Yes.

The incidence of cancers has a strong link to environmental exposures, particularly lifestyle and diet. Any lifestyle and diet habits that lead to energy excess (too much food, too little exercise) have been linked with cancers through metabolic dysfunction, inflammation, and oxidative stress 9.

Besides greatly reducing, or completely omitting alcohol, other lifestyle changes could be incorporated to mitigate the risk of alcohol-induced cancers.

Exercise, high fiber diets (and/or the Mediterranean diet), cessation of smoking, and balancing of the gut flora all have positive effects in reducing cancer risk9.

What about the Blue Zones?

A “Blue Zone” is a term given to geographic regions where some of the world’s oldest people are found. These areas are highly concentrated with nonagenarians (90+ years old) and centenarians (100+ years old), and in some of them, the population is known to drink daily.

There are five known Blue Zones:

  • Nicoya Peninsula (Costa Rica): The Nicoyan diet consists mainly of beans and corn tortillas, where the majority of this population perform physical jobs into old age.
  • Icaria (Greece): Icaria is an island where people eat a Mediterranean diet rich in olive oil, red wine, homegrown vegetables, and very little meat.
  • The Seventh-day Adventists in Loma Linda, California (USA): The Seventh-day Adventists are a very religious population and are strict vegetarians.
  • Ogliastra, Sardinia (Italy): The Ogliastra region is home to some of the oldest men in the world. They live in mountainous regions and typically work on farms to produce their own food, and drink red wine daily.
  • Okinawa (Japan): Okinawa is home to the world’s oldest women. Their diets are rich in soy-based foods. They also practice tai chi, a meditative form of exercise.

You’ll see that there are a few similarities between the five Blue Zones:

  • Very little to no meat
  • Exercise
  • Alcohol in the form of red wine

You’re probably wondering how alcohol consumption can increase cancer risk in populations outside of these Blue Zones but not have these effects on the Blue Zone populations.

Well, the beneficial effect of moderate alcohol consumption is likely to depend on the type of alcohol. Research suggests that red wine may be the ‘healthiest’ type of alcohol to drink since it contains several antioxidants from grapes. In fact, Sardinian Cannonau wine, made from Grenache grapes, was found to have extremely high levels of antioxidants when compared to other wines.

Analysis of the diets in the Blue Zones found that consuming one to two glasses of red wine per day is common in the Icarian and Sardinian Blue Zones.

So, although people in these Blue Zones are classified as moderate drinkers, other healthy lifestyle habits are followed, such as very little/no red meat, and homegrown vegetables, plus the inclusion of moderate exercise. These habits appear to outweigh the effect of moderate alcohol consumption and lead to a longer, healthier life.

Dr. Gina Leisching

Dr. Gina Leisching holds a BSc in Functional Human Biology, and Honours degree in Physiological Sciences, as well as a doctorate in human physiology from Stellenbosch University, South Africa. At Gene Food, Dr. Gina uses her expertise to provide evidence-pieces that readers may find helpful and informative.

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