The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer from Alcohol Consumption

Approximately 36% of East Asians (Japanese, Chinese, and Koreans) show a characteristic physiological response to drinking alcohol that includes facial flushing (see Figure 1), nausea, and tachycardia [1] . This so-called alcohol flushing response (also known as “Asian flush” or “Asian glow”) is predominantly due to an inherited deficiency in the enzyme aldehyde dehydrogenase 2 (ALDH2) [2]. Although clinicians and the East Asian public generally know about the alcohol flushing response (e.g., http://www.echeng. com/asianblush/), few are aware of the accumulating evidence that ALDH2-deficient individuals are at much higher risk of esophageal cancer (specifically squamous cell carcinoma) from alcohol consumption than individuals with fully active ALDH2. This is particularly unfortunate as esophageal cancer is one of the deadliest cancers worldwide [3], with five-year survival rates of 15.6% in the United States, 12.3% in Europe, and 31.6% in Japan [4]. Our goal in writing this article is to inform doctors firstly that their ALDH2-deficient patients have an increased risk for esophageal cancer if they drink moderate amounts of alcohol, and secondly that the alcohol flushing response is a biomarker for ALDH2 deficiency. Because of the intensity of the symptoms, most people who have the alcohol flushing response are aware of it. Therefore clinicians can determine ALDH2 deficiency simply by asking about previous episodes of alcohol-induced flushing. As a result, ALDH2-deficient patients can then be counseled to reduce alcohol consumption, and high-risk patients can be assessed for endoscopic cancer screening. Based on the sizes of the Japanese, Chinese, and Korean populations and the expected frequency of ALDH2-deficient individuals in each [1], we estimate that there are at least 540 million ALDH2deficient individuals in the world, representing approximately 8% of the population. In a population of this size, even a small reduction in the incidence of esophageal cancer could result in a substantial reduction in esophageal cancer deaths worldwide.