title: Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14.
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.
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK.
authors.forename: Elise
authors.initials: E
authors.lastname: Ruark
authors.forename: Sheila
authors.initials: S
authors.lastname: Seal
authors.forename: Heather
authors.initials: H
authors.lastname: McDonald
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Anna
authors.initials: A
authors.lastname: Elliot
authors.forename: Kingwai
authors.initials: K
authors.lastname: Lau
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Perdeaux
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rapley
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
authors.forename: Julian
authors.initials: J
authors.lastname: Peto
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kote-Jarai
authors.forename: Kenneth
authors.initials: K
authors.lastname: Muir
authors.forename: Jeremie
authors.initials: J
authors.lastname: Nsengimana
authors.forename: Janet
authors.initials: J
authors.lastname: Shipley
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Robert A
authors.initials: RA
authors.lastname: Huddart
authors.forename: Nazneen
authors.initials: N
authors.lastname: Rahman
authors.forename: Clare
authors.initials: C
authors.lastname: Turnbull
mesh_terms: D004268:DNA-Binding Proteins; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012307:Risk Factors; D013736:Testicular Neoplasms / Q000235:genetics*; D014157:Transcription Factors
chemical_list: C101358:DAZL protein, human; D004268:DNA-Binding Proteins; C524724:PRDM14 protein, human; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors