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NIH/National Institute on Alcohol Abuse and Alcoholism
Alcohol 'flush' signals increased cancer risk among East Asians
Many people of East Asian descent
possess an enzyme deficiency that causes their skin to redden, or
flush, when they drink alcohol. Scientists from the National Institute
on Alcohol Abuse and Alcoholism (NIAAA) and Japan's Kurihama Alcohol
Center now caution that heavy alcohol consumption greatly increases the
risk for esophageal cancer among such individuals, who comprise about 8
percent of the world's population. Their review of recent research on
this topic appears in the March 24, 2009 issue of
PLoS Medicine. NIAAA is part of the National Institutes of Health.
is very important for clinicians who treat patients of East Asian
descent to be aware of the risk of esophageal cancer from alcohol
consumption in their patients who exhibit the alcohol flushing
response, so they can counsel them about limiting their drinking," says
NIAAA Acting Director Kenneth R. Warren, Ph.D.
Philip J. Brooks, Ph.D., of NIAAA's Laboratory of Neurogenetics, and
his colleagues note that a clinician can reliably determine whether a
patient is at risk simply by asking about previous episodes of facial
flushing after drinking alcohol. Considered from this perspective, the
authors point out, the flushing response is a clinically useful
biomarker of genetic susceptibility to esophageal cancer risk from
Dr. Brooks cites the high mortality from esophageal
cancer and the large number of individuals with the deficient enzyme,
known as aldehyde dehydrogenase 2 (ALDH2).
"Cancer of the
esophagus is particularly deadly, with five-year survival rates ranging
from 12 to 31 percent throughout the world. And we estimate that at
least 540 million people have this alcohol-related increased risk for
esophageal cancer," he notes. "We hope that, by raising awareness of
this important public health problem, affected individuals who drink
will reduce their cancer risk by limiting their alcohol consumption."
Brooks and his colleagues explain that ALDH2 plays an important role in
alcohol metabolism. When alcohol is consumed, it is first metabolized
into acetaldehyde, a chemical similar to formaldehyde, which causes DNA
damage and has other cancer-promoting effects. ALDH2 is the main enzyme
responsible for breaking down acetaldehyde into acetate, a non-toxic
metabolite in the body.
East Asians have two main variants of
the ALDH2 gene -- one that produces an enzyme with normal activity, and
another that results in an inactive enzyme. When individuals with the
inactive variant drink alcohol, acetaldehyde accumulates in the body,
resulting in facial flushing, nausea, and rapid heartbeat. For people
with two copies of the inactive variant, these symptoms are so severe
that they can drink very little alcohol. However, individuals with only
one copy of the inactive variant can become tolerant to the unpleasant
effects of acetaldehyde, which puts them at risk for alcohol-related
A series of epidemiologic studies by Akira
Yokoyama and his colleagues in Japan have shown that individuals with
one copy of the inactive variant are about 6-10 times more likely to
develop esophageal cancer than are individuals with the fully active
ALDH2 enzyme who drink comparable amounts of alcohol. Notably, these
studies showed that individuals with the inactive variant who drink the
equivalent of 33 or more U.S. standard drinks per week have a 89-fold
increased risk of esophageal cancer compared to non-drinkers. Dr.
Yokoyama is a co-author of the latest report.
add that many ALDH2-deficient university students may have their first
experiences with heavy drinking while in college. Therefore, it is
particularly important for university health professionals to be aware
of the relationship between ALDH2-deficiency, facial flushing, and
alcohol-related cancer risk. Informing ALDH2-deficient young people of
their risk of esophageal cancer from alcohol drinking represents a
valuable and cost-effective opportunity for cancer prevention.
National Institute on Alcohol Abuse and Alcoholism, part of the
National Institutes of Health, is the primary U.S. agency for
conducting and supporting research on the causes, consequences,
prevention, and treatment of alcohol abuse, alcoholism, and alcohol
problems. NIAAA also disseminates research findings to general,
professional, and academic audiences. Additional alcohol research
information and publications are available at www.niaaa.nih.gov.
National Institutes of Health (NIH) — The Nation's Medical Research
Agency — includes 27 Institutes and Centers and is a component of the
U. S. Department of Health and Human Services. It is the primary
Federal agency for conducting and supporting basic, clinical, and
translational medical research, and it investigates the causes,
treatments, and cures for both common and rare diseases. For more
information about NIH and its programs, visit http://www.nih.gov.
Brooks PJ, Enoch M-A, Goldman D, Li T-K, and Yokoyama A. (2009) The
Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal
Cancer from Alcohol Consumption.
PLoS Medicine. Vol. 6 No. 3: e1000050. doi:10.1371/journal.pmed.1000050