A genome-wide association study on medulloblastoma.
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Dahlin AM
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
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Wibom C
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
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Andersson U
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
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Bybjerg-Grauholm J
Danish Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
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Deltour I
Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France.
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Hougaard DM
Danish Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
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Scheurer ME
Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.
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Lau CC
Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA.
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McKean-Cowdin R
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
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Kennedy RJ
Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA, USA.
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Hung LT
Department of Pediatrics, Section of Hematology-Oncology, Children's Hospital Los Angeles and The Saban Research Institute, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
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Yee J
Department of Pediatrics, Section of Hematology-Oncology, Children's Hospital Los Angeles and The Saban Research Institute, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
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Margol AS
Department of Pediatrics, Section of Hematology-Oncology, Children's Hospital Los Angeles and The Saban Research Institute, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
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Barrington-Trimis J
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
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Gauderman WJ
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
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Feychting M
Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
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Schüz J
Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France.
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Röösli M
Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland.
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Kjaerheim K
The Cancer Registry of Norway, Oslo, Norway.
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Januszkiewicz-Lewandowska D
Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland.
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Fichna M
Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
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Nowak J
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
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Searles Nielsen S
Department of Pediatrics, Section of Hematology-Oncology, Children's Hospital Los Angeles and The Saban Research Institute, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
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Asgharzadeh S
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
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Mirabello L
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
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Hjalmars U
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. beatrice.melin@umu.se.
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Melin B
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Published in:
- Journal of neuro-oncology. - 2020
English
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.
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Language
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Open access status
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hybrid
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Persistent URL
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https://sonar.ch/global/documents/270833
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