Associations between variants in KITLG, SPRY4, BAK1, and DMRT1 and pediatric germ cell tumors

Genes Chromosomes Cancer. 2012 Mar;51(3):266-71. doi: 10.1002/gcc.20951. Epub 2011 Nov 10.


Recent genome wide association studies have identified susceptibility loci for adult testicular germ cell tumors (GCT) near KITLG, SPRY4, BAK1, and DMRT1. We evaluated variants in these four genes to determine whether these are also susceptibility loci for pediatric GCTs. DNA was isolated from 52 pediatric GCTs (ages 0-21 years) obtained from the Cooperative Human Tissue Network. Control DNA was isolated from de-identified dried blood spots from 141 white newborns. Genotyping was conducted using TaqMan assays (rs4474514) or by PCR and sequencing (rs4324715, rs210138, and rs755383). Associations between variants and GCT were evaluated using logistic regression with adjustment for sex. We also evaluated whether the associations differed by age at GCT diagnosis (0-9 years, 10-21 years), sex, and tumor location (gonadal, non-gonadal). We observed a significant association for rs210138 (BAK1) and pediatric GCT overall (odds ratio (OR) = 1.80, 95% confidence interval (CI) 1.10-2.95, P = 0.02) with non-significant associations similar in magnitude in both the pediatric (P = 0.09) and adolescent (P = 0.06) age groups. The KITLG (rs4474514) and SPRY4 (rs4324715) variants were significantly associated with GCT only in the adolescent age group (rs4474514: OR = 2.28, 95% CI 1.09-4.79, P = 0.03 and rs4324715: OR = 2.40, 95% CI 1.19-4.83, P = 0.01). Associations were mostly similar when stratified by sex. This is the first study to suggest that these loci may also be important in susceptibility to GCTs in the adolescent (KITLG, SPRY4, and BAK1) and pediatric (BAK1) age groups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Child
  • Child, Preschool
  • Endodermal Sinus Tumor / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Infant, Newborn
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Molecular Typing
  • Neoplasms, Germ Cell and Embryonal / genetics*
  • Nerve Tissue Proteins / genetics*
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Sex Factors
  • Stem Cell Factor / genetics*
  • Teratoma / genetics*
  • Testicular Neoplasms / genetics*
  • Transcription Factors / genetics
  • Young Adult
  • bcl-2 Homologous Antagonist-Killer Protein / genetics*


  • BAK1 protein, human
  • DMRT1 protein
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • SPRY4 protein, human
  • Stem Cell Factor
  • Transcription Factors
  • bcl-2 Homologous Antagonist-Killer Protein