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 - Funding Information:
Open access funding provided by Umeå University. We acknowledge the role of the late Dr. Mads V. Hollegaard in this study. Dr. Hollegaard was included in all parts of the study, with most important contributions in the conceptualization and formal analyses. The Cefalo Study Group includes Michaela Prochazka, Maral Adel Fahmideh, Birgitta Lannering, Lisbeth S. Schmidt, Christoffer Johansen, Astrid Sehested, Claudia Kuehni, Michael Grotzer, Tore Tynes, Tone Eggen, and Lars Klæboe. We are grateful for the support early in the study by Dr. Bent Nørgaard-Pedersen at the Danish Neonatal Screening Biobank and the assistance in sample collection by Dr. Ulrika von Döbeln at the Swedish phenylketonuria screening registry. This research was funded by the Swedish Childhood Cancer Foundation (Grant Nos. NCS2009-0001, PR2017-0157, NC2011-0004, and TJ2015-0044); the Acta Oncologica Foundation through The Royal Swedish Academy of Science; the Swedish Cancer Foundation (Grant No. CAN 2018/390); the Swedish Research Council (Grant No. 2016-01159_3) ; the Cancer Research Foundation in Northern Sweden (Grant Nos. LP 14-2044, LP 10-1842); Umeå University Hospital (Cutting Edge Grant) (Grant Nos. 7002485, 7002994); and NIH-NIEHS grant, P30ES007033, R01CA116724 and R03CA106011. This research has been conducted using the Danish National Biobank resource, supported by the Novo Nordisk Foundation. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.
Funding Information:
Open access funding provided by Umeå University. We acknowledge the role of the late Dr. Mads V. Hollegaard in this study. Dr. Hollegaard was included in all parts of the study, with most important contributions in the conceptualization and formal analyses. The Cefalo Study Group includes Michaela Prochazka, Maral Adel Fahmideh, Birgitta Lannering, Lisbeth S. Schmidt, Christoffer Johansen, Astrid Sehested, Claudia Kuehni, Michael Grotzer, Tore Tynes, Tone Eggen, and Lars Klæboe. We are grateful for the support early in the study by Dr. Bent Nørgaard-Pedersen at the Danish Neonatal Screening Biobank and the assistance in sample collection by Dr. Ulrika von Döbeln at the Swedish phenylketonuria screening registry. This research was funded by the Swedish Childhood Cancer Foundation (Grant Nos. NCS2009-0001, PR2017-0157, NC2011-0004, and TJ2015-0044); the Acta Oncologica Foundation through The Royal Swedish Academy of Science; the Swedish Cancer Foundation (Grant No. CAN 2018/390); the Swedish Research Council (Grant No. 2016-01159_3) ; the Cancer Research Foundation in Northern Sweden (Grant Nos. LP 14-2044, LP 10-1842); Umeå University Hospital (Cutting Edge Grant) (Grant Nos. 7002485, 7002994); and NIH-NIEHS grant, P30ES007033, R01CA116724 and R03CA106011. This research has been conducted using the Danish National Biobank resource, supported by the Novo Nordisk Foundation. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.
Publisher Copyright:
© 2020, The Author(s).
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
SN - 0167-594X
VL - 147
SP - 309
EP - 315
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 2
ER -