CCND2, CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 gene variants and risk of childhood medulloblastoma.
Recent studies have described a number of genes that are frequently altered in medulloblastoma tumors and that have putative key roles in the development of the disease. We hypothesized that common germline genetic variations in these genes may be associated with medulloblastoma development. Based on recent publications, we selected 10 genes that were frequently altered in medulloblastoma: CCND2, CTNNB1, DDX3X, GLI2, SMARCA4, MYC, MYCN, PTCH1, TP53, and MLL2 (now renamed as KMT2D). Common genetic variants (single nucleotide polymorphisms) annotating these genes (n = 221) were genotyped in germline DNA (neonatal dried blood spot samples) from 243 childhood medulloblastoma cases and 247 control subjects from Sweden and Denmark. Eight genetic variants annotating three genes in the sonic hedgehog signaling pathway; CCND2, PTCH1, and GLI2, were found to be associated with the risk of medulloblastoma (P(combined) < 0.05). The findings were however not statistically significant following correction for multiple testing by the very stringent Bonferroni method. The results do not support our hypothesis that common germline genetic variants in the ten studied genes are associated with the risk of developing medulloblastoma.
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. anna.dahlin@umu.se.
Anna M
AM
Dahlin
Department of Congenital Disorders, Danish Centre for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark.
Mads V
MV
Hollegaard
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
Carl
C
Wibom
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
Ulrika
U
Andersson
Department of Congenital Disorders, Danish Centre for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark.
David M
DM
Hougaard
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.
Isabelle
I
Deltour
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
Ulf
U
Hjalmars
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
Beatrice
B
Melin
D000293:Adolescent; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D056742:Cyclin D2 / Q000235:genetics*; D003718:Denmark; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D008527:Medulloblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D012189:Retrospective Studies; D013548:Sweden; D055815:Young Adult; D000075746:Zinc Finger Protein Gli2
C080336:CCND2 protein, human; D056742:Cyclin D2; C082593:GLI2 protein, human; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D000075746:Zinc Finger Protein Gli2
Genetic association studies; Genetic variation; Medulloblastoma; PNET; Primitive neuroectodermal tumors