Effect of UGT2B17 deletion polymorphism on prognosis in pediatric cancer.

Background The UDP-glucuronosyltransferase 2 family, polypeptide B17 (UGT2B17) gene encodes an enzyme that modifies carcinogens, C19 steroids, xenobiotics, and anticancer chemotherapeutic agents by glucuronidation. Pediatric cancers are much more sensitive to anticancer agents than adult cancers. Therefore, we examined the effects of a deletion polymorphism in the UGT2B17 gene on prognosis in pediatric cancer. Methods A total of 145 DNA samples were collected from children with malignant diseases. Copy number variants (CNVs) of the UGT2B17 gene were determined using polymerase chain reaction (PCR). Survival analyses were computed to analyze effects of UGT2B17 gene deletion on relapse-free rates in lymphoblastic and nonlymphoblastic malignancies. Results The UGT2B17 gene was deleted in 64% of children with lymphoblastic malignancies but in 83% of children with nonlymphoblastic malignancies. Moreover, in nonlymphoblastic malignancies, children without deletion polymorphism in the UGT2B17 gene had significantly higher relapse rates than those with the deletion polymorphism (hazard ratio, 16.1; 95% confidence interval [CI], 1.67–154; P = 0.016), which remained significant (P = 0.032) after adjustment for age, sex, underlying diseases, advanced stage, and adverse events (HR, 22.4; 95% CI, 1.10–454; P = 0.043). There was a significant interaction between UGT2B17 gene deletion and nonlymphoblastic malignancies. In the early subgroup, i.e., stage 1–3 or standard/intermediate risk, children without a deletion polymorphism in the UGT2B17 gene showed higher relapse rates than children with more advanced disease (log-rank test: P = 0.0004). Conclusions Deletion polymorphism in the UGT2B17 gene may improve the relapse-free rate in children with nonlymphoblastic malignancies. This article is protected by copyright. All rights reserved.