Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer

Nat Genet. 2009 Jul;41(7):811-5. doi: 10.1038/ng.393. Epub 2009 May 31.

Abstract

Testicular germ cell tumors (TGCT) have been expected to have a strong underlying genetic component. We conducted a genome-wide scan among 277 TGCT cases and 919 controls and found that seven markers at 12p22 within KITLG (c-KIT ligand) reached genome-wide significance (P < 5.0 x 10(-8) in discovery). In independent replication, TGCT risk was increased threefold per copy of the major allele at rs3782179 and rs4474514 (OR = 3.08, 95% CI = 2.29-4.13; OR = 3.07, 95% CI = 2.29-4.13, respectively). We found associations with rs4324715 and rs6897876 at 5q31.3 near SPRY4 (sprouty 4; P < 5.0 x 10(-6) in discovery). In independent replication, risk of TGCT was increased nearly 40% per copy of the major allele (OR = 1.37, 95% CI = 1.14-1.64; OR = 1.39, 95% CI = 1.16-1.66, respectively). All of the genotypes were associated with both seminoma and nonseminoma TGCT subtypes. These results demonstrate that common genetic variants affect TGCT risk and implicate KITLG and SPRY4 as genes involved in TGCT susceptibility.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Chromosomes, Human, Pair 5*
  • European Continental Ancestry Group / genetics
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Male
  • Neoplasms, Germ Cell and Embryonal / genetics*
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Oligonucleotide Array Sequence Analysis
  • Philadelphia
  • Stem Cell Factor / genetics*
  • Testicular Neoplasms / genetics*
  • Testicular Neoplasms / pathology

Substances

  • Stem Cell Factor