Objective To investigate the correlation between drinking behavior combined with polymorphisms of extracellular superoxide dismutase (EC-SOD) and aldehyde dehydrogenase-2 (ALDH2) genes and pancreatic cancer. Methods The genetic polymorphisms of EC-SOD and ALDH2 were analyzed by polymerase chain reaction restriction fragment length polymorphism in the peripheral blood leukocytes obtained from 680 pancreatic cancer cases and 680 non-cancer controls. Subsequently the frequency of genotype was compared between the pancreatic cancer patients and the healthy controls.The relationship of drinking with pancreatic cancer was analyzed. Results The frequencies of EC-SOD (C/G) and ALDH2 variant genotypes were 37.35% and 68.82% respectively in the pancreatic cancer cases

and were significantly higher than those in the healthy controls (21.03% and 44.56%

all P<0.01). People who carried EC-SOD (C/G) (OR=2.24

95% CI= 1.81-4.03

P<0.01) or ALDH2 variant genotypes (OR=2.75

95% CI=1.92-4.47

P<0.01) had a high risk to develop pancreatic cancer. Those who carried EC-SOD (C/G) genotype combined with ALDH2 variant genotype had a high risk for pancreatic cancer (29.56% vs. 6.76%

OR=7.69

95% CI=3.58-10.51

P<0.01). The drinking rate of the pancreatic cancer group (64.12%) was significantly higher than that of the control group (40.15%; OR=2.66

95% CI=1.30-4.42

P<0.01). An interaction between drinking and EC-SOD (C/G)/ALDH2 variant genotypes increased the risk of occurrence of pancreatic cancer (OR=25.00

95% CI= 11.87-35.64

P<0.01). Conclusion EC-SOD (C/G)

ALDH2 variant genotypes and drinking might be the risk factors of pancreatic cancer.