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Genetic Variants in the 9p21.3 Locus Associated with Glioma Risk in Children, Adolescents, and Young Adults: A Case-Control Study
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.ORCID iD: 0000-0002-6754-2571
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
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2019 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 28, no 7, p. 1252-1258Article in journal (Refereed) Published
Abstract [en]

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 and 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 years and 3,689 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 = 5.8 × 10−4). In genome-wide analysis, an association with risk was suggested for 129 genetic variants (P <1 × 10−5).

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.

Place, publisher, year, edition, pages
American Association for Cancer Research , 2019. Vol. 28, no 7, p. 1252-1258
National Category
Cancer and Oncology Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
URN: urn:nbn:se:umu:diva-162886DOI: 10.1158/1055-9965.EPI-18-1026ISI: 000481682500019PubMedID: 31040135OAI: oai:DiVA.org:umu-162886DiVA, id: diva2:1348336
Available from: 2019-09-04 Created: 2019-09-04 Last updated: 2019-09-04Bibliographically approved

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Dahlin, Anna M.Wibom, CarlAndersson, UlrikaHjalmars, UlfMelin, Beatrice S.

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