Common variants identified in genome-wide association studies of testicular germ cell tumour: an update, biological insights and clinical application

Andrology. 2015 Jan;3(1):34-46. doi: 10.1111/andr.304. Epub 2015 Jan 19.


Testicular germ cell tumour (TGCT) is the most common cause of cancer in young men (aged 15-45 years) in many populations. Multiple genome-wide association studies (GWAS) of TGCT have now been conducted, yielding over 25 disease-associated single-nucleotide polymorphism (SNP)s at 19 independent loci. The genes at these loci have provided rich biological and genetic insight into possible mechanisms underlying testicular germ cell oncogenesis. In this review, we summarize these mechanisms which can be grouped into five distinct categories: KIT/KITLG signalling, other pathways of male germ cell development/differentiation, telomerase function, microtubule assembly and DNA damage repair. The TGCT risk markers identified through GWAS include individual SNPs carrying per allele odds ratios (OR) in excess of 2.5. These ORs are among the highest reported in GWAS of any cancer type, hence suggesting a potential clinical utility in risk determination. Here, we present analysis of such an approach, using polygenic risk scores to calculate the combined effect of all risk loci on overall TGCT risk and discuss how a potential screening strategy may fit within a broader clinical context.

Keywords: cancer; genome-wide association studies; genome-wide sequencing; single-nucleotide polymorphism; testis cancer.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / genetics*
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Neoplasms, Germ Cell and Embryonal / epidemiology
  • Neoplasms, Germ Cell and Embryonal / genetics*
  • Neoplasms, Germ Cell and Embryonal / metabolism
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Testicular Neoplasms / epidemiology
  • Testicular Neoplasms / genetics*
  • Testicular Neoplasms / metabolism
  • Testicular Neoplasms / pathology
  • Young Adult


  • Biomarkers, Tumor