Identification of four new susceptibility loci for testicular germ cell tumour

Nat Commun. 2015 Oct 27:6:8690. doi: 10.1038/ncomms9690.


Genome-wide association studies (GWAS) have identified multiple risk loci for testicular germ cell tumour (TGCT), revealing a polygenic model of disease susceptibility strongly influenced by common variation. To identify additional single-nucleotide polymorphisms (SNPs) associated with TGCT, we conducted a multistage GWAS with a combined data set of >25,000 individuals (6,059 cases and 19,094 controls). We identified new risk loci for TGCT at 3q23 (rs11705932, TFDP2, P=1.5 × 10(-9)), 11q14.1 (rs7107174, GAB2, P=9.7 × 10(-11)), 16p13.13 (rs4561483, GSPT1, P=1.6 × 10(-8)) and 16q24.2 (rs55637647, ZFPM1, P=3.4 × 10(-9)). We additionally present detailed functional analysis of these loci, identifying a statistically significant relationship between rs4561483 risk genotype and increased GSPT1 expression in TGCT patient samples. These findings provide additional support for a polygenic model of TGCT risk and further insight into the biological basis of disease development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Cohort Studies
  • DNA-Binding Proteins / genetics*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neoplasms, Germ Cell and Embryonal / genetics*
  • Nuclear Proteins / genetics*
  • Peptide Termination Factors / genetics*
  • Polymorphism, Single Nucleotide
  • Testicular Neoplasms / genetics*
  • Transcription Factors / genetics*
  • Young Adult


  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • GAB2 protein, human
  • Nuclear Proteins
  • Peptide Termination Factors
  • TFDP2 protein, human
  • Transcription Factors
  • ZFPM1 protein, human
  • peptide-chain-release factor 3

Supplementary concepts

  • Testicular Germ Cell Tumor