Genetic Variants in the 9p21.3 Locus Associated with Glioma Risk in Children, Adolescents, and Young Adults: A Case-Control Study.


Journal

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608

Informations de publication

Date de publication:
07 2019
Historique:
received: 20 09 2018
revised: 07 01 2019
accepted: 26 04 2019
pubmed: 2 5 2019
medline: 10 9 2020
entrez: 2 5 2019
Statut: ppublish

Résumé

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. 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. Three adult glioma risk variants, rs634537, rs2157719, and rs145929329, all mapping to the 9p21.3 ( 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. 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.

Sections du résumé

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 (
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.

Identifiants

pubmed: 31040135
pii: 1055-9965.EPI-18-1026
doi: 10.1158/1055-9965.EPI-18-1026
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1252-1258

Informations de copyright

©2019 American Association for Cancer Research.

Auteurs

Anna M Dahlin (AM)

Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. anna.dahlin@umu.se.

Carl Wibom (C)

Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.

Ulrika Andersson (U)

Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.

David M Hougaard (DM)

Department of Congenital Disorders, Danish Centre for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark.

Jonas Bybjerg-Grauholm (J)

Department of Congenital Disorders, Danish Centre for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark.

Isabelle Deltour (I)

Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France.
Unit of Statistics, Bioinformatics and Registry, Danish Cancer Society Research Center, Copenhagen, Denmark.

Christina M Hultman (CM)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Icahn School of Medicine at Mount Sinai, New York, New York.

Anna K Kähler (AK)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Robert Karlsson (R)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Ulf Hjalmars (U)

Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.

Beatrice Melin (B)

Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.

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