Inactive aldehyde dehydrogenase-2 increased the risk of pancreatic cancer among smokers in a Japanese male population

Objectives: Most of the acetaldehyde, a recognized animal carcinogen, generated during alcohol metabolism is eliminated by liver mitochondrial aldehyde dehydrogenase 2 (ALDH2). More than 40% of Japanese have the inactive form of ALDH2, and inactive ALDH2 is a risk factor for multiple cancers of the esophagus as well as head and neck cancer. Possible associations between pancreatic cancer and ALDH2 gene polymorphism, in conjunction with smoking and/or drinking habits, were examined in a Japanese population. Methods: We investigated 114 patients ( 70 male and 44 female) with pancreatic cancer and compared them with 2070 control subjects ( 1050 male and 1020 female). The drinking ( 5 g ethanol consumption/ d) and/or smoking habits as well as ALDH2 gene polymorphism were examined. Results: In male subjects, the frequency of the active form of ALDH2 (2*1/2*1) was lower in pancreatic cancer patients than in control subjects ( P = 0.018). The frequency of subjects with both smoking and drinking habits was significantly higher in pancreatic cancer patients than in control subjects having ALDH2*1/2*1 and ALDH2*1/2*2. The frequency of smoking habit alone was significantly higher in pancreatic cancer patients compared with control subjects having inactive ALDH2. Drinking habit had no relation to pancreatic cancer. In female subjects, neither habit had a relation to pancreatic cancer. Conclusions: Smoking habit did increase the risk of pancreatic cancer, and this risk was further enhanced in subjects with inactive ALDH2 in a male population but not in a female population. There was no relationship between drinking habit and pancreatic cancer in either sex population.