title: Familial testicular germ cell tumours.
abstract: This article defines familial testicular germ cell tumours (FTGCTs) as testicular germ cell tumours (TGCTs) diagnosed in at least two blood relatives, a situation which occurs in 1-2% of all cases of TGCT. Brothers and fathers of TGCT patients have an 8-10- and 4-6-fold increased risk of TGCT, respectively, and an even higher elevated risk of TGCT in twin brothers of men with TGCT has been observed, suggesting that genetic elements play an important role in these tumours. Nevertheless, previous linkage studies with multiple FTGCT families did not uncover any high-penetrance genes and it has been concluded that the combined effects of multiple common alleles, each conferring a modest risk, might underlie FTGCT. In agreement with this assumption, recent candidate gene-association analyses have identified the chromosome Y gr/gr deletion and mutations in the PDE11A gene as genetic modifiers of FTGCT risk. Moreover, two genome-wide association studies of predominantly sporadic but also familial cases of TGCT have identified three additional susceptibility loci, KITLG, SPRY4 and BAK1. Notably, all five loci are involved in the biology of primordial germ cells, representing the cell of origin of TGCT, suggesting that the tumours arise as a result of disturbed testicular development.
authors.affiliation: Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20852, USA.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Kratz
authors.forename: Phuong L
authors.initials: PL
authors.lastname: Mai
authors.forename: Mark H
authors.initials: MH
authors.lastname: Greene
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D041322:Chromosomes, Human, Y; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000235:genetics; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics
chemical_list: C494772:BAK1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C499038:SPRY4 protein, human; D050998:bcl-2 Homologous Antagonist-Killer Protein; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C406737:PDE11A protein, human