Gene-08. common genetic variations in cell cycle and dna repair pathways associated with pediatric brain tumor susceptibility

Abstract BACKGROUND: Knowledge on the role of genetic polymorphisms in the etiology of pediatric brain tumors (PBTs) is limited. Therefore, we investigated the association between single nucleotide polymorphisms (SNPs), identified by candidate gene-association studies on adult brain tumors, and PBT risk. METHODS: The study is based on the largest series of PBT cases to date. Saliva DNA from 245 cases and 489 controls, aged 7–19 years at diagnosis/reference date, was genotyped for 68 SNPs. Data were analyzed using unconditional logistic regression. Stratified analyses were conducted for two histological subtypes: astrocytoma alone and other tumor types combined. RESULTS:EGFR rs730437 (p=0.002) and EGFR rs11506105 (p=0.036) may decrease susceptibility to PBTs, whereas ERCC1 rs3212986 (p=0.009) may increase risk of these tumors. Moreover, stratified analyses indicated that CHAF1A rs243341, CHAF1A rs2992, and XRCC1 rs25487 were associated with a decreased risk of astrocytoma subtype (pDOM=0.040, pDOM=0.049, and pDOM=0.033, respectively). In addition, an increased risk of non-astrocytoma tumor subtype associated with EGFR rs9642393, EME1 rs12450550, ATM rs170548, and GLTSCR1 rs1035938 (pREC=0.021, pREC=0.001, pDOM=0.041, and pREC=0.027, respectively) as well as a decreased risk of this subtype associated with XRCC4 rs7721416 (pREC=0.032) and XRCC4 rs2662242 (pREC=0.024) were detected. CONCLUSIONS: This study indicates that SNPs in EGFR, ERCC1, CHAF1A, XRCC1, EME1, ATM, GLTSCR1, and XRCC4 may be associated with the risk of PBTs. Therefore, genetic polymorphisms in cell cycle and DNA repair pathways associated with susceptibility to adult brain tumors also seem to be associated with PBT risk, suggesting that pediatric and adult brain tumors might share similar etiological pathways.