Facial flushing after alcohol consumption can be more than a mere social embarrassment. Research has found that the flushing response caused by a mutant enzyme puts people at high risk for a deadly cancer — and not everyone can feel the toxic warning signs.

The flushing response is nothing new, but the writers of “The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer from Alcohol Consumption,” published in the Public Library of Science Medicine journal, found that many doctors and their aldehyde dehydrogenase 2 (ALDH2) deficient patients are unaware of the link between a mutant enzyme and esophageal cancer. 

“Esophagus cancer is one of the deadliest, killing seven out of eight of its victims, and only 15 percent pass the five-year survival rate,” said Dr. Patrick Bradshaw, USF bioscience researcher and professor. “It’s especially important to educate university students and their physicians because (college) is when students typically start experimenting with heavy drinking.”

The alcohol flushing response is caused by a deficiency in the ALDH2 enzyme. Those who have it are 10 times more likely to get esophageal cancer. ALDH2 is responsible for metabolizing alcohol into acetaldehyde, a toxic substance similar to formaldehyde, and then into a non-toxic substance comparable to vinegar. People with the deficiency aren’t able to metabolize the toxic substance, so it accumulates, causing the face to flush.

Some with the deficiency have an unpleasant, nauseous reaction to alcohol and are unable to consume it in large amounts. These people are actually protected against the increased chances of cancer, while those without unpleasant responses continue to drink and may lead themselves to a toxic demise.

“Everyone has two copies of the trait, but some have two inactive variants and others have one active and one inactive,” Bradshaw said. “Those with one active and one inactive are the ones able to better tolerate alcohol.”

Clinical tests used to assess ALDH2 deficiency are simple, including a questionnaire asking if the participant has a tendency to develop facial flushing immediately after drinking one glass of alcohol, and an ethanol patch test that allows ethanol to absorb into skin on the inner surface of the upper arm for seven minutes to see if it turns red.

The deficient ALDH2 trait affects more than one-third of people of East Asian decent, but Bradshaw said it isn’t entirely impossible for others to have the deficiency.

Those without the ALDH2 deficiency are not safe from getting alcohol-induced esophageal cancer. The H. Lee Moffitt Cancer Center and Research Institute’s Dr. Kenneth Meredith, a surgical oncologist specializing in gastrointestinal oncology, treats a variety of patients suffering from esophageal cancer — the youngest being college-aged.

“It’s very common for people to develop esophageal cancer because the cells lining the body transform when DNA damage occurs, such as with the carcinogens in alcohol and tobacco,” Meredith said.

Signs of esophageal cancer, often not apparent at first, include weight loss, inability to tolerate liquids and a feeling of solid foods becoming stuck upon swallowing. The
cancerous damage looks like a tumor cluster, often white in color, and the tissue easily frays, causing bleeding. The cancer is able to invade muscle walls, spreading to lymph nodes and other areas.

The esophagus starts at the throat and continues into the intestinal region, so it is possible for cancer to develop at any point in the muscle. If the cancer is in the upper half, the entire esophagus must be removed.

“Surgeries can last four to six and a half hours, depending on whether the patient needs an open surgery, consisting of a single large incision, or closed surgery involving multiple millimeter-sized incisions,” Meredith said. “Patients typically need six to 10 days in the hospital for surgery recovery.”

Patients are classified according to how far the cancer has progressed to determine whether they should undergo chemotherapy or radiation rather than surgery. A process called staging rates tumor thickness, invasion of muscle wall and whether the cancer has spread to other organs, and is usually conducted using a scope passed from the mouth to the small intestine.

Meredith concentrates his research in trying to predict which patients will fare best with which therapy and will pass the five-year survival rate. He said the cancer is typically found in men, but he has seen an increase in the number of women diagnosed. He suggests that those with acid reflux as well as heavy and moderate smokers and drinkers should talk to their doctor.