Clinical and Genetic Risk Prediction of Subsequent CNS Tumors in Survivors of Childhood Cancer: A Report From the COG ALTE03N1 Study

PurposeSurvivors of childhood cancer treated with cranial radiation therapy are at risk for subsequent CNS tumors. However, significant interindividual variability in risk suggests a role for genetic susceptibility and provides an opportunity to identify survivors of childhood cancer at increased risk for these tumors.MethodsWe curated candidate genetic variants from previously published studies in adult-onset primary CNS tumors and replicated these in survivors of childhood cancer with and without subsequent CNS tumors (82 participants and 228 matched controls). We developed prediction models to identify survivors at high or low risk for subsequent CNS tumors and validated these models in an independent matched case-control sample (25 participants and 54 controls).ResultsWe demonstrated an association between six previously published single nucleotide polymorphisms (rs15869 [BRCA2], rs1805389 [LIG4], rs8079544 [TP53], rs25489 [XRCC1], rs1673041 [POLD1], and rs11615 [ERCC1]) and subsequent CNS tumors in s...