Esophageal Squamous Cell Carcinoma and Aldehyde Dehydrogenase-2 Genotypes in Japanese Females


  • This work was supported by a Grant-in-Aid for Cancer Research 12-12 from the Ministry of Health, Labor and Welfare of Japan.

Reprint requests: Akira Yokoyama, National Hospital Organization Kurihama Alcoholism Center, 5-3-1 Nobi, Yokosuka, Kanagawa 239-0841, Japan; E-mail:


Background: Aldehyde dehydrogenase-2 (ALDH2) is the key enzyme for elimination of acetaldehyde, an established animal carcinogen produced after drinking. In persons with inactive ALDH2, the body fails to metabolize acetaldehyde rapidly, leading to excessive accumulation of acetaldehyde. Inactive heterozygous ALDH2 enhances the risk of esophageal squamous cell carcinoma (SCC) in Japanese male drinkers.

Methods: We studied whether this is the case for women. The risk factors of esophageal SCC were examined in 52 Japanese women with esophageal SCC and 412 cancer-free Japanese women.

Results: The increasing trend in cancer risk according to the quantity of alcohol consumption was significantly steeper in women with inactive heterozygous ALDH2 than in those with active ALDH2 [adjusted odds ratios (ORs) (95% confidence intervals (CIs)) per +7 U/wk increment of alcohol drinking were 3.91 (2.09–7.31) and 1.39 (0.92–2.09), respectively; p=0.006 for difference in OR; 1 Ut=22 g of ethanol]. The results obtained using an alcohol-flushing questionnaire were essentially comparable with those obtained by ALDH2 genotyping [adjusted ORs (95% CIs) per +7 U/wk increment of alcohol drinking were 3.94 (1.87–8.31) and 1.46 (0.96–2.23) in those with and without flushing, respectively; p=0.021 for difference in OR]. The risk of esophageal cancer was markedly higher in heavy drinkers with ALDH2*1/*2 than in never/rare drinkers with ALDH2*1/*1 [adjusted OR (95% CI)=59.1 (4.65–750)]. Other independent significant risk factors of esophageal SCC were smoking, a preference for hot food or drinks, and lower intake of green and yellow vegetables.

Conclusions: Japanese men and women shared several common risk factors of esophageal SCC, including drinking with inactive heterozygous ALDH2.