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Alcohol Consumption, Smoking and Risk of Esophageal Cancer
Intended for research and educational purposes. Not for diagnostic use.

Your Genetic Data

Your result - Reduced ability to break down acetaldehyde, a toxic byproduct of alcohol and cigarette smoke. As a result, you are likely to have increased odds of esophageal cancer, especially if you drink or smoke.

Technical Report - Detected the following mutations: ALDH2*2

Other Name(s)ALDH2*2   
DNA Change: G to A   
Genotype: AG (variant present)

Only a medical professional can determine the right medication for a particular patient. This information should not be used to independently establish or adjust an existing regimen.

The Genetics of Alcohol Consumption, Smoking and Risk of Esophageal Cancer
Acetaldehyde is a highly toxic substance known to cause cancer. It occurs naturally in a variety of food and beverages, is found in cigarette smoke, and is a breakdown product of alcohol.

The body normally converts acetaldehyde into a harmless substance called acetate. But many people with East Asian ancestry have a mutation in the aldehyde dehydrogenase gene (ALDH2) that prevents this reaction, leading to a build-up of acetaldehyde and the "alcohol flush" often seen in this population. The mutation, called ALDH2*2, has not been found in people who trace their ancestors back to Europe or Africa.

On its own, the increase in saliva acetaldehyde caused by the ALDH2*2 mutation about doubles the odds of esophageal cancer. Alcohol and cigarette smoke also each raise the odds of the disease by about two times. But when a person with the ALDH2*2 mutation drinks and/or smokes, these risk factors work together to dramatically increase risk. The magnitude of the combined effect varies from study to study, but the basic finding that these three risk factors synergistically increase the risk of esophageal cancer is definitive.

In one of the largest studies done to date (Cui, 2009), researchers found that in ALDH2*2 carriers who smoke, the odds of esophageal cancer were between 5.65 and 23.08 higher than non-carriers who did not smoke or drink. The wide range in risk has to do with the presence or absence of another genetic risk factor prevalent in East Asians that is not covered in this report.

Unable to break down acetaldehyde, a toxic byproduct of alcohol and cigarette smoke. As a result, you are likely to have greatly increased odds of esophageal cancer, especially if you drink or smoke, although too few individuals with your genotype who also drank were studied to constitute a meaningful sample size.

Normal ability to break down acetaldehyde, a toxic byproduct of alcohol and cigarette smoke. No increase in odds of esophageal cancer due to genotype, but alcohol consumption and smoking are still risk factors.

Sensitivity to alcohol— the alcohol flush reaction—depends almost entirely on a person's genotype at two genes, ALDH2 and ADH1B. 23andMe currently reports your genotype at a SNP in ALDH2. It is possible that those with the AG or GG genotypes at the SNP are more sensitive to alcohol due to their genotype at ADH1B (which 23andMe does not report).

Notes from 23AndMe:

Alcohol is a social lubricant for some and an addictive substance for others. But for people with the alcohol flush reaction, alcohol has such an unpleasant, noxious effect that they tend to avoid it altogether. Even a single drink may cause people sensitive to alcohol to become dizzy or nauseous, have headaches, and turn bright red. The alcohol flush reaction is primarily due to variations in two genes that encode proteins responsible for breaking down alcohol in the bloodstream.

The Wrath of Grapes

Alcoholic drinks have been around as long as civilization itself (and possibly longer). Beer and wine have both been described in the written records of ancient Egypt and Mesopotamia. Like many discoveries, the first alcoholic drink was probably an accident, when cereal grains or berries were left out and fermented by yeast in the air. (A similar accident may also have given rise to the other product of the hugely successful human-yeast partnership: leavened bread.)

The first brave soul to try what was essentially spoiled food was a lucky one, as many food-borne microbes, like salmonella or botulism, are very toxic or even fatal. The waste product of brewer's yeast is ethanol—the chemical name for alcohol—moderate amounts of which interact with the brain to produce the pleasant effects of intoxication, like being less shy or more relaxed.

Genetic variation also influences how well you can hold your liquor. Ethanol is poisonous in larger doses, so our bodies have evolved ways to break it down before it has a chance to build up. While your brain is enjoying its temporary loss of inhibition, your liver is doing its best to clear the alcohol out of your system before it kills you.

The liver's ultimate goal is to turn ethanol into harmless acetic acid (i.e. vinegar), which can be easily removed in urine. The problem is that in order to become vinegar, ethanol has to be converted to acetaldehyde, which is as nasty as it sounds. In fact, acetaldehyde is even more toxic than ethanol. Some of the effects of drinking—turning red, increased heart rate—are actually symptoms of acetaldehyde poisoning. Certain versions of genes can cause a logjam in ethanol processing and a buildup of acetaldehyde. If you have these versions, even one drink can result in ill effects, like flushing, dizziness, nausea, and headaches.

The genotypes that result in a buildup of acetaldehyde when drinking alcohol happen to be especially common in Asians compared to Europeans. This is the reason the ill effects are known in some circles as the "Asian flush."

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12 discoveries from 7000 B.C. to 1994.

7000 B.C.
Inhabitants of the neolithic village of Jiahu in Henan province in China make a fermented beverage of rice, honey, and fruit (hawthorn fruit and/or grape). Chemical analyses of ancient organics absorbed into pottery jars reveal their recipe in the 21st century. (sources)

2100 B.C.
The Sumerians use alcohol as a form of medicine and record its use on a cuneiform tablet of pharmacopeia. (sources)

1000 B.C.
Archaeological evidence shows that fermented cacao beverages were being made in Mesoamerica before 1000 B.C. (sources)

800 A.D.
The process of distillation is invented by the Arabian alchemist Jabir (or Geber) ibn Hayyan. He may also have named the distillate alcohol, which derives from the Arabic root, al-kuhul. Al-kuhul originally referred to powdered antimony (kohl) used as an eye cosmetic but with time it came to mean the "essence," and eventually, the essence of wine—its spirit, or alcohol. (sources)

1947
Disulfiram, a drug that inhibits aldehyde dehydrogenase was discovered by accident at the Royal Danish School of Pharmacy in Copenhagen, Denmark, by Danish researchers Eric Jacobsen and Jens Hald. The two were studying compounds to be used for treating parasitic stomach infections. Both men took a small dose of disulfiram to check for possible side effects. At a cocktail party several days later, they both became very ill after having a drink. They concluded that the disulfiram had interacted with the alcohol to trigger the illness. (sources)

1951
Disulfiram is approved by the FDA as a drug to treat alcohol abuse. Its brand name is Antabuse. It discourages a drinker's desire for alcohol by causing extremely unpleasant symptoms (including facial flushing) when a drink is taken. (sources)

1971
Researchers show that disulfiram inhibits the function of aldehyde dehydrogenase. (sources)

1972
To find if the lower incidence of alcoholism in Asians vs. Europeans is due to cultural or biological factors, Wolff conducts an experiment looking at the physiological reactions to alcohol in both adults and infants from both ethnic groups. He finds that many Asians exhibit a pronounced facial flushing when given alcohol. He concludes that since infants showed the same variation in alcohol response as adults, cultural factors and drinking habits could not be at work. The cause must be genetic. (sources)

1979
The absence of the enzyme coded by ALDH2, which is a common occurrence in people of Asian ancestry, is hypothesized to cause alcohol intolerance. (sources)

1980
Experiments show that livers from Japanese autopsies typically show two forms of aldehyde dehydrogenase enzyme. This finding provides evidence for how genetic differences might lead to phenotypic differences in alcohol sensitivity. (sources)

1991
Researchers publish a study of ALDH2 genotypes in Chinese, showing that alcoholics are less likely to have the slow version of acetaldehyde dehydrogenase. This observation lends support to the hypothesis that the same mechanism that leads to the alcohol flush reaction—a buildup of acetaldehyde due to a slow enzyme—protects against alcoholism. (sources)

1994
A group of biochemists show that the two versions of the ALDH2 gene commonly seen in Asians encode two versions of the aldehyde dehydrogenase protein with strikingly different biochemical properties. This evidence connects genetic differences to phenotypic differences by providing a biochemical mechanism. (sources)

Everyone burns alcohol at a slightly different rate. But experts agree, the burn rate ranges from .010 g/10ml/hr to .025 g/100ml/hr.

The state Patrol analyzed all our data and found that the average burn rate for the volunteers who took Sobrietol was .019. That is on the high side of normal, but still well within the normal range.

We asked State Toxicologist Dr. Barry Logan to look at our results and comment on them.

"There are I think, some exaggerated claims about the product, that are certainly not supported by your tests,�  he said.

I asked Dr. Logan if the subjects in our test burned alcohol any faster than they normally would be expected to?

“No,"  he said. "There didn't seem to be any significant rate of increase in the rate of burn off in the subjects taking the Sobrietol."

We did a two day test. One day of drinking with Sobrietol, and one without to see if the claims are true. Five volunteers, three bottles of booze, and a team of alcohol experts from various agencies helped us put Sobrietol through a non-scientific test...

For example, Shane started at a .05 the previous night. On Sobrietol, he had a .02. That is a drop of more than 50 percent. Jeremy had similar results, and our other three volunteers' blood alcohol levels dropped by about forty percent.

Our results were basically what he expected of his product. What Pratt didn't expect was our volunteers' reaction to the Sobrietol. It didn't go down well and it didn't sit well. Here is what the volunteers had to say during the test:

"It doesn't feel drunk. It just doesn't feel pleasant," and "I see vomit in our future."

That wasn't the only issue with Sobrietol...

Let me assure you, Eric, that this is irrelevant to you and your readership, as are (*hopefully*) most articles in the Journal of the American Geriatric Society!

What this paper is talking about is the fact that use of H2-blockers (and all other medications with anticholinergic effects) can increase cognitive problems in the elderly. In those people who experience cognitive decline while using such medications, discontinuation of the offending agent typically relieves the impairment. Suffice it to say, though, that those most affected are usually those with the poorest cognitive substrate in the first place.

Regardless, this article should NOT give pause to young people who use H2-blockers, whatever the regularity of use.