TY - JOUR
T1 - A genome-wide association study on medulloblastoma
AU - The Cefalo Study Group
AU - Dahlin, Anna M.
AU - Wibom, Carl
AU - Andersson, Ulrika
AU - Bybjerg-Grauholm, Jonas
AU - Deltour, Isabelle
AU - Hougaard, David M.
AU - Scheurer, Michael E.
AU - Lau, Ching C.
AU - McKean-Cowdin, Roberta
AU - Kennedy, Rebekah J.
AU - Hung, Long T.
AU - Yee, Janis
AU - Margol, Ashley S.
AU - Barrington-Trimis, Jessica
AU - Gauderman, W. James
AU - Feychting, Maria
AU - Schüz, Joachim
AU - Röösli, Martin
AU - Kjaerheim, Kristina
AU - Prochazka, Michaela
AU - Adel Fahmideh, Maral
AU - Lannering, Birgitta
AU - Schmidt, Lisbeth S.
AU - Johansen, Christoffer
AU - Sehested, Astrid
AU - Kuehni, Claudia
AU - Grotzer, Michael
AU - Tynes, Tore
AU - Eggen, Tone
AU - Klæboe, Lars
AU - Januszkiewicz-Lewandowska, Danuta
AU - Fichna, Marta
AU - Nowak, Jerzy
AU - Searles Nielsen, Susan
AU - Asgharzadeh, Shahab
AU - Mirabello, Lisa
AU - Hjalmars, Ulf
AU - Melin, Beatrice
N1 - Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark. Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2. Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3). Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.
AB - Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark. Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2. Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3). Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.
KW - Adolescents and young adults (AYA)
KW - CNS cancers
KW - Epidemiology
KW - Genetics of risk, outcome, and prevention
KW - Pediatric cancers
UR - http://www.scopus.com/inward/record.url?scp=85079528189&partnerID=8YFLogxK
U2 - 10.1007/s11060-020-03424-9
DO - 10.1007/s11060-020-03424-9
M3 - Article
C2 - 32056145
AN - SCOPUS:85079528189
VL - 147
SP - 309
EP - 315
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 2
ER -