Effect of UGT2B17 deletion polymorphism on prognosis in pediatric cancer.

BACKGROUND: UDP-glucuronosyltransferase 2 family, polypeptide B17 (UGT2B17) encodes for 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. The aim of this study was therefore to examine the effects of UGT2B17 deletion polymorphism on prognosis in pediatric cancer.

METHODS: A total of 145 DNA samples were collected from children with malignant disease. UGT2B17 copy number variant was determined on polymerase chain reaction. Survival analysis was carried out to analyze the effects of UGT2B17 deletion on relapse-free rate in lymphoblastic and non-lymphoblastic malignancy.

RESULTS: UGT2B17 was deleted in 64% of children with lymphoblastic malignancy, but in 83% of children with non-lymphoblastic malignancy. Moreover, in non-lymphoblastic malignancy, children without UGT2B17 deletion polymorphism had significantly higher relapse rates than those with the deletion polymorphism (HR, 16.1; 95%CI: 1.67-154; P = 0.016), which remained significant after adjustment for age, sex, underlying disease, advanced stage, and adverse events (HR, 22.4; 95%CI: 1.10-454; P = 0.043). There was a significant interaction between UGT2B17 deletion and non-lymphoblastic malignancy. In the early subgroup, that is, stages 1-3 or standard/intermediate risk, children without UGT2B17 deletion polymorphism had a higher relapse rate than children with more advanced disease (log-rank test: P = 0.0004).

CONCLUSIONS: UGT2B17 deletion polymorphism may improve the relapse-free rate in children with non-lymphoblastic malignancy.