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UGT2B17 Deletion Polymorphism is a Risk Factor for Upper Aero digestive-Tract Cancer in Japanese: A Case-Control Study

Urashima M*, Nakashima A, Hama T, Suzuki Y, Ohdaira H, Akiba T, Suzuki M, Noya M, Tsumi Y, Mafune A, Toda K, Yokoyama K, Wada K, Kojima H and Okamoto A

Background: The UDP-glucuronosyltransferase 2 family polypeptide B17 (UGT2B17) detoxifies carcinogens found in tobacco smoke and ethanol in alcoholic drinks. Tobacco carcinogens and ethanol synergistically raise the risk for upper aero digestive tract (UADT) cancer (head and neck squamous carcinoma, and esophageal cancer). Deletion polymorphism of the UGT2B17 gene (UGT2B17-deletion) is a much more common copy number variant among Japanese than other populations. Thus, we conducted a nested and age/gender-matched case-control (1:1) study to determine if UGT2B17-deletion associates with cancer risk, including UADT-cancer in Japanese.

Methods: Polymerase chain reaction was used to determine UGT2B17-deletion using DNA samples derived from peripheral blood or tumor tissue. Cases were cancer patients and controls were non-cancer patients. Nonconditional and conditional logistic regression analyses were performed. To overcome the issue of multiple-testing, Bonferroni correction was applied to set p < 0.003 as statistically significant.

Results: A total of 3,092 patients were enrolled. UGT2B17-deletion was detected in 74% of the 1,887 non-cancer patients and 77% of the 1,205 cancer patients. UGT2B17-deletion was a significant risk factor for UADT-cancer development: odds ratio, 2.07; 95% confidence interval, 1.34 to 3.20, p=0.001. In contrast, UGT2B17-deletion was not a risk for any other type of cancers represented in our study population.

Conclusions: These results suggest that UGT2B17-deletion may associate to increase the risk of UADT-cancer in Japanese.