Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14

Nat Genet. 2013 Jun;45(6):686-9. doi: 10.1038/ng.2635. Epub 2013 May 12.

Abstract

Testicular germ cell tumor (TGCT) is the most common cancer in young men and is notable for its high familial risks. So far, six loci associated with TGCT have been reported. From genome-wide association study (GWAS) analysis of 307,291 SNPs in 986 TGCT cases and 4,946 controls, we selected for follow-up 694 SNPs, which we genotyped in a further 1,064 TGCT cases and 10,082 controls from the UK. We identified SNPs at nine new loci (1q22, 1q24.1, 3p24.3, 4q24, 5q31.1, 8q13.3, 16q12.1, 17q22 and 21q22.3) showing association with TGCT (P < 5 × 10(-8)), which together account for an additional 4-6% of the familial risk of TGCT. The loci include genes plausibly related to TGCT development. PRDM14, at 8q13.3, is essential for early germ cell specification, and DAZL, at 3p24.3, is required for the regulation of germ cell development. Furthermore, PITX1, at 5q31.1, regulates TERT expression and is the third TGCT-associated locus implicated in telomerase regulation.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Linkage Disequilibrium
  • Male
  • Neoplasms, Germ Cell and Embryonal / genetics*
  • Polymorphism, Single Nucleotide
  • RNA-Binding Proteins / genetics*
  • Repressor Proteins / genetics*
  • Risk Factors
  • Testicular Neoplasms / genetics*

Substances

  • DAZL protein, human
  • PRDM14 protein, human
  • RNA-Binding Proteins
  • Repressor Proteins

Supplementary concepts

  • Testicular Germ Cell Tumor