Genetic polymorphisms of uridine diphosphate-glucuronosyltransferases 1A6 (UGT1A6) and 1A7 (UGT1A7)may lead to genetic instability and colorectal cancer carcinogenesis. Our objective was to measure the interactionbetween polymorphisms of these repair genes and tobacco smoking in colorectal cancer (CRC). A total of 68individuals with CRC and 112 non-cancer controls were divided into non-smoker and smoker groups accordingto pack-years of smoking. Genetic polymorphisms of UGT1A6 and UGT1A7 were examined using polymerasechain reaction-restriction fragment length polymorphism (PCR-RFLP). We found a weak association ofUGT1A6 polymorphisms with CRC risk (crude odds ratio [OR], 1.65; 95% confidence interval [95%CI], 0.9-3.1,P=0.107; adjusted OR 1.95, 95%CI 1.0-3.8, P=0.051). The ORs for the UGT1A7 polymorphisms were statisticallysignificant (crude OR: 26.40, 95%CI: 3.5-198.4, P=0.001; adjusted OR: 21.52, 95%CI: 2.8-164.1, P=0.003). Thejoint effect of tobacco exposure and UGT1A6 polymorphisms was significantly associated with colorectal cancerrisk in non-smokers (crude OR, 2.11; 95%CI, 0.9-5.0, P=0.092; adjusted OR 2.63, 95%CI 1.0-6.7, P=0.042). Inconclusion, our findings suggest that UGT1A6 and UGT1A7 gene polymorphisms are associated with CRC riskin the Japanese population. In particular, UGT1A6 polymorphisms may strongly increase CRC risk throughthe formation of carcinogens not associated with smoking.