Genetic Variants in the 9p21.3 Locus Associated with Glioma Risk in Children, Adolescents, and Young Adults: a Case-control Study
Menée en Suède et au Danemark auprès de 3 689 témoins et de 854 personnes atteintes d'un gliome diagnostiqué avant l'âge de 29 ans, cette étude identifie 3 variants génétiques du locus 9p21.3 associés au risque de développer la maladie
Résumé en anglais
Background : Genome-wide association studies have identified germline genetic variants in 25 genetic loci that increase the risk of developing glioma in adulthood. It is not known if these variants increase the risk of developing glioma in children, adolescents and young adults (AYA). To date, no studies have performed genome-wide analyses to find novel genetic variants associated with glioma risk in children and AYA.
Methods : We investigated the association between 8,831,628 genetic variants and risk of glioma in 854 patients diagnosed up to the age of 29 and 3689 controls from Sweden and Denmark. Recruitment of patients and controls was population-based. Genotyping was performed using Illumina BeadChips, and untyped variants were imputed with IMPUTE2. We selected 41 established adult glioma risk variants for detailed investigation.
Results : Three adult glioma risk variants, rs634537, rs2157719, and rs145929329, all mapping to the 9p21.3 (CDKN2B-AS1) locus, were associated with glioma risk in children and AYA. The strongest association was seen for rs634537 (odds ratioG=1.21; 95% confidence interval=1.09-1.35; p=5.8x10-4). In genome-wide analysis, an association with risk was suggested for 129 genetic variants (p-value<1x10-5).
Conclusions : Carriers of risk alleles in the 9p21.3 locus have an increased risk of glioma throughout life. The results from genome-wide association analyses require validation in independent cohorts.
Impact : Our findings line up with existing evidence that some, although not all, established adult glioma risk variants are associated with risk of glioma in children and AYA. Validation of results from genome-wide analyses may reveal novel susceptibility loci for glioma in children and AYA.
